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1. Glycyrrhizic acid modulates t-BHP induced apoptosis in primary rat hepatocytes.

Tripathi M, Singh BK, Kakkar P.

Herbal Research Section, Indian Institute of Toxicology Research, P.O. Box 80, MG Marg, Lucknow 226001, India.

Glycyrrhizic acid (GA) is the main bioactive ingredient of licorice (Glycyrrhiza glabra). The object of this study was to evaluate the protective effects of GA on tert-butyl hydroperoxide (t-BHP) induced oxidative injury leading to apoptosis in cultured primary rat hepatocytes. Throughout the study silymarin was used as positive control. Molecular mechanisms involved in apoptotic pathways induced in hepatocytes by t-BHP at 250muM were explored in detail. DNA fragmentation, activation of caspases and cytochrome c release were demonstrated. In addition, changes in the mitochondrial membrane potential and ROS generation were detected confirming involvement of mitochondrial pathway. Pre-treatment with GA (4mug) protected the hepatocytes against t-BHP induced oxidative injury and the results were comparable to the pre-treatment with positive control, i.e. silymarin. The protective potential against cell death was achieved mainly by preventing intracellular GSH depletion, decrease in ROS formation as well as inhibition of mitochondrial membrane depolarization. GA was found to modulate critical end points of oxidative stress induced apoptosis and could be beneficial against liver diseases where oxidative stress is known to play a crucial role.

PMID: 19084568 [PubMed - as supplied by publisher]

2. Isoliquiritigenin, a flavonoid from licorice, plays a dual role in regulating gastrointestinal motility in vitro and in vivo.

Chen G, Zhu L, Liu Y, Zhou Q, Chen H, Yang J.

Department of Pharmacology, School of Medicine, Wuhan University, Donghu Road, Wuhan 430071, China.

Licorice root has been used for years to regulate gastrointestinal function in traditional Chinese medicine. This study reveals the gastrointestinal effects of isoliquiritigenin, a flavonoid isolated from the roots of Glycyrrhiza glabra (a kind of Licorice). In vivo, isoliquiritigenin produced a dual dose-related effect on the charcoal meal travel, inhibitory at the low doses, while prokinetic at the high doses. In vitro, isoliquiritigenin showed an atropine-sensitive concentration-dependent spasmogenic effect in isolated rat stomach fundus. However, a spasmolytic effect was observed in isolated rabbit jejunums, guinea pig ileums and atropinized rat stomach fundus, either as noncompetitive inhibition of agonist concentration-response curves, inhibition of high K(+) (80 mM)-induced contractions, or displacement of Ca(2+) concentration-response curves to the right, indicating a calcium antagonist effect. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME; 30 microM), indomethacin (10 microM), methylene blue (10 microM), tetraethylammonium chloride (0.5 mM), glibenclamide (1 microM), 4-aminopyridine (0.1 mM), or clotrimazole (1 microM) did not inhibit the spasmolytic effect. These results indicate that isoliquiritigenin plays a dual role in regulating gastrointestinal motility, both spasmogenic and spasmolytic. The spasmogenic effect may involve the activating of muscarinic receptors, while the spasmolytic effect is predominantly due to blockade of the calcium channels. Copyright (c) 2008 John Wiley & Sons, Ltd.

PMID: 19067384 [PubMed - as supplied by publisher]
3. In vitro effects of glycyrrhetinic acid on the growth of clinical isolates of Candida albicans.

Pellati D, Fiore C, Armanini D, Rassu M, Bertoloni G.

Department of Histology, Microbiology and Medical Biotechnologies, Via Gabelli, 63, 35121-Padua, University of Padua, Italy.

Compounds derived from Glycyrrhiza glabra L. root have been used widely for centuries for their numerous therapeutic properties. The present study aimed to test the in vitro activity against Candida albicans strains of the compound 18-beta glycyrrhetinic acid (18-beta GA), derived from the root of Glycyrrhiza species. This antimicrobial activity was assessed using the National Committee for Clinical Laboratory Standards (NCCLS) method on C. albicans strains that were isolated from patients with recurrent vulvovaginal candidiasis (RVVC). The in vitro growth of the C. albicans strains was markedly reduced, in a pH-dependent manner, by relatively low doses (6.2 microg/mL) of 18-beta GA. The results demonstrate that 18-beta GA is a promising biological alternative for the topical treatment of recurrent vulvovaginal candidiasis (RVVC). Copyright (c) 2008 John Wiley & Sons, Ltd.

PMID: 19067381 [PubMed - as supplied by publisher]

4. Investigation of the anti-obesity action of licorice flavonoid oil in diet-induced obese rats.

Kamisoyama H, Honda K, Tominaga Y, Yokota S, Hasegawa S.

Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe, Japan.

Licorice flavonoid oil (LFO), which contains hydrophobic flavonoids from Glycyrrhiza glabra LINNE, is a new ingredient for functional foods. In this study, we investigated the anti-obesity action of LFO in diet-induced obese rats. The addition of 2% LFO in a high-fat diet significantly decreased the weight of abdominal adipose tissue and the levels of hepatic and plasma triglycerides. We found that the enzymatic activities of acetyl-CoA carboxylase and fatty acid synthase, the rate-limiting enzymes in the fatty acid synthetic pathway, were significantly decreased by LFO, whereas the enzymatic activity of acyl-CoA dehydrogenase, the rate-limiting enzyme in the fatty acid oxidative pathway, was significantly increased. All our findings suggest that the anti-obesity action of LFO is controlled by regulation of the rate-limiting enzymes in the fatty acid synthetic and oxidative pathways in the liver.

Publication Types: PMID: 19060415 [PubMed - in process]

5. Screening of antiplasmodial properties traditionally used among some Iranian plants.

Esmaeili S, Naghibi F, Mosaddegh M, Sahranavard S, Ghafari S, Abdullah NR.

School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran; Traditional Medicine and Materia Medica Research Center (TMRC), Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

ETHNOPHARMACOLOGICAL RELEVANCE: An investigation of plants was undertaken through interviews and literature surveys on plants used to treat malaria or cancer or microbial diseases in Iran. AIM OF STUDY: In vitro and in vivo antiplasmodial tests were carried out on selected plants traditionally used in Iran. MATERIALS AND METHODS: Thirty-two plants were extracted with methanol and tested for their in vitro (pLDH assay) activity against Plasmodium falciparum, in vivo activity against Plasmodium berghei and assessed for any cytotoxicity against the human cancer cell line MCF7 and the normal cell MDBK. RESULTS: Extracts from four plants, Buxus hyrcana Pojark. (Buxaceae), Erodium oxyrrhnchum M. Bieb. (Geraniaceae), Glycyrrhiza glabra L. (Fabaceae) and Ferula oopoda (Boiss and Bushe) Boiss. (Apiaceae) were found to have significant antiplasmodial activity (IC(50) ranging from 4.7 to 26.6mug/ml). These findings lend support to the use of Buxus hyrcana and Glycyrrhiza glabra in traditional medicine. The chloroformic fraction also was active against K1 and 3D7 strains. The chloroformic fraction was studied at 10mg per kg body weight mouse per day. This fraction reduced parasitaemia by 86.1% compared to untreated control mice. CONCLUSION: Glycyrrhiza glabra showed antiplasmodial activity and has selectivity for Plasmodium falciparum and Plasmodium berghei when tested on mammalian cells. This is the first report that mentioned in vitro and in vivo antiplasmodial activity of Glycyrrhiza glabra.

PMID: 19059470 [PubMed - as supplied by publisher]

6. Retinopathy induced by drugs and herbal medicines.

Nencini C, Barberi L, Runci FM, Micheli L.

Dipartimento di Farmacologia Giorgio Segre, Universitŕ degli Studi di Siena, Italy.

Retina is the part of the eye suffering most damage from drugs. It is made up of a thin nervous membrane that covers the eye-ball internally, within the thickness of which three types of cells are ordered. In this paper we describe the drugs that are responsible for retinal side effects. Most commonly recognized drugs-induced retinopathy have a particular affinity for the retinal pigmented epithelium: antimalarials (quinine, hydroxychloroquine, mefloquine), phenothiazines, indomethacin, ethambutol, and desferrioxamine. Attention is especially focused on drugs more recently suspected of adverse reactions in the retina: vigabatrin, gabapentin, sildenafil, tamoxifen, isotretinoin, interferon, and omeprazole. Moreover, we referred some reports of retinopathy by herbal medicines and nutritional supplements (canthaxanthine, Gingko biloba L. and Glycyrrhiza glabra L.) This review is based on data published in scientific journals indexed by the PubMed and Medline databases. The last search of the literature was conducted in April 2008.

Publication Types: PMID: 19024212 [PubMed - indexed for MEDLINE]

7. Free radical scavenging activity, metal chelation and antioxidant power of some of the Indian spices.

Yadav AS, Bhatnagar D.

School of Biochemistry, Devi Ahilya University, Indore, Madhya Pradesh, India.

Food constituents are the major source of various phytochemicals and micronutrients. The importance of these dietary constituents has been stressed in recent years due to their antioxidant and anticarcinogenic potential. Spices used in Indian foods such as cloves (Syzygium aromaticum), licorice (Glycyrrhiza glabra), mace (aril of Myristica fragans), and greater cardamom (Amomum subulatum) were tested for their antioxidant properties in vitro. The metal chelating activity, bleomycin dependent DNA oxidation, diphenyl-p-picryl hydrazyl (DPPH) radical scavenging activity and the ferric reducing /antioxidant power (FRAP) were measured in rat liver homogenate in presence of spices. Metal chelating activity was significantly high with all the spice extracts except mace. The spices due to higher reducing potential (in presence of bleomycin-FeCl_{3}) showed increased DNA oxidation. Cloves showed the highest DPPH radical scavenging activity, followed by licorice, mace and cardamom. FRAP values for cloves were also the highest, while other spices showed comparatively lesser FRAP values. The results show that the spices tested are strong antioxidants and may have beneficial effects on human health.

PMID: 18997285 [PubMed - in process]
8. Mesorhizobium gobiense sp. nov. and Mesorhizobium tarimense sp. nov., isolated from wild legumes growing in desert soils of Xinjiang, China.

Han TX, Han LL, Wu LJ, Chen WF, Sui XH, Gu JG, Wang ET, Chen WX.

Key Laboratory of Agro-Microbial Resource and Application, Ministry of Agriculture/College of Biological Sciences, China Agricultural University, Beijing 100193, PR China.

Twenty-four Mesorhizobium strains were isolated from desert soils in the Xinjiang region of China and were characterized by a polyphasic approach. These strains grouped into three clusters in IGS-RFLP, SDS-PAGE analysis of whole-cell proteins and BOX-PCR analysis, corresponding to genomic species V, VI and VII as found in a previous study. The results were supported by sequencing analyses of rrs, IGS, atpD and recA genes. Genospecies VII was most related to Mesorhizobium septentrionale, while genospecies V and VI were both most closely related to Mesorhizobium tianshanense, but were distinct from each other and from M. tianshanense. The DNA-DNA hybridization value between the representative strain CCBAU 83284 (genospecies VII) and the type strain of M. septentrionale was 90.1 %. Genospecies VII was thus defined as M. septentrionale. The DNA-DNA relatedness value for representative strains of genospecies V or VI with the related reference strains of recognized species were always lower than 60 %. Low values of DNA-DNA hybridization (32.79 %) between representative strains of genospecies V (CCBAU 83330(T)) and of VI (CCBAU 83306(T)) were also observed. Based upon these results, two novel species are proposed: Mesorhizobium gobiense sp. nov. represented by genospecies V (type strain, CCBAU 83330(T)=LMG 23949(T)=HAMBI 2974(T)) and Mesorhizobium tarimense sp. nov. represented by genospecies VI (type strain, CCBAU 83306(T)=LMG 24338(T)=HAMBI 2973(T)). Strain CCBAU 83278 grouped as the most peripheral member with genospecies VI in SDS-PAGE of whole-cell proteins and BOX-PCR analysis and in the phylogenetic tree of 16S-23S rRNA intergenic spacer (IGS) sequences. The results of analyses of rrs, atpD and recA gene sequences, as well as those of DNA-DNA hybridization studies, strongly supported the suggestion that this strain belonged to a species quite different from genospecies V and VI and from any other recognized species of the genus Mesorhizobium. As only one strain has been isolated to date, strain CCBAU 83278 was not proposed as a novel species in this study. Mesorhizobium gobiense sp. nov. and Mesorhizobium tarimense sp. nov. could be differentiated from each other as well as from recognized species of the genus Mesorhizobium on the basis of phenotypic characteristics. The symbiotic loci (nodC and nifH) of the two novel species formed two phylogenetic branches related to Mesorhizobium loti and M. tianshanense. The type strains of the two novel species were able to nodulate Glycyrrhiza uralensis, Lotus corniculatus, Oxytropis glabra and Robinia pseudoacacia but not Astragalus membranaceus, Leucaena leucocephala, Phaseolus vulgaris, Pisum sativum or Medicago sativa.

Publication Types: PMID: 18984702 [PubMed - in process]

9. Anti-proliferative effect of licochalcone A on vascular smooth muscle cells.

Park JH, Lim HJ, Lee KS, Lee S, Kwak HJ, Cha JH, Park HY.

Division of Cardiovascular and Rare Diseases, Center for Biomedical Sciences, NIH, Seoul, Republic of Korea.

Licochalcone A, a flavonoid found in licorice root (Glycyrrhiza glabra), is known for its anti-microbial activity and its reported ability to inhibit cancer cell proliferation. In the present study, we investigated whether licochalcone A inhibits rat vascular smooth muscle cell (rVSMC) proliferation. Our data indicate that 5 microM licochalcone A inhibited platelet-derived growth factor (PDGF)-induced rVSMC proliferation, possibly through its ability to block the progression of the cell cycle from G1 to S phase. In addition, 5 microM licochalcone A significantly inhibited the PDGF-induced expression of cyclin A, cyclin D1, CDK2, and CDK4, and the phosphorylation of Rb. Licochalcone A also reversed the decrease in p27(kip1) expression reduced by PDGF. Finally, licochalcone A inhibited the PDGF-induced activation of extracellular signal-regulated kinase (ERK)1/2. Together, these data provide the first evidence that licochalcone A can regulate rVSMC proliferation and suggest that licochalcone A inhibits the proliferation of rVSMCs by suppressing the PDGF-induced activation of the ERK1/2 pathway and Rb phosphorylation, resulting in cell cycle arrest.

Publication Types: PMID: 18981562 [PubMed - in process]

10. Screening of Nepalese crude drugs traditionally used to treat hyperpigmentation: in vitro tyrosinase inhibition.

Adhikari A, Devkota HP, Takano A, Masuda K, Nakane T, Basnet P, Skalko-Basnet N.

The School of Pharmaceutical and Biomedical Sciences, Pokhara University, Pokhara, PO Box 427, Pokhara, Nepal. adhikarianjana@gmail.com

South-East Asian population is daily exposed to strong sunlight. As a result, the majority of population will have darker, ethnic skin. Moreover, many people suffer from dark spots, hyperpigmentation, which is considered to be a skin disorder and causes psychological disturbance. To treat dark spots, most of the population will still rely on traditionally used crude drugs, knowledge about which is transferred from generation to generation. Fifty-two crude drugs were selected based on the survey performed among local healers and beauticians of different ethnic origin. These crude drugs were screened for mushroom tyrosinase inhibitory activity, as tyrosinase inhibitors are becoming increasingly important as cosmetic and medicinal products, primarily to control hyperpigmentation. Among the tested crude drugs, methanolic extracts of Glycyrrhiza glabra, Morus alba, Syzygium aromaticum, Citrus aurantifolia, Cypreae moneta, Punica granatum and Citrus aurantium, at the final concentration of 50 microg mL(-1), showed mushroom tyrosinase inhibitory activity of 78.9%, 71.0%, 69.4%, 59.0%, 56.0%, 53.4 and 51.9%, respectively, with 91.4% inhibitory activity of kojic acid taken as positive control. To our knowledge, this is the first report that extracts of Cypreae moneta shell and Syzygium aromaticum flowering bud have tyrosinase inhibitory activity. These potent extracts were further evaluated at different concentration. The final concentration of the extracts in reaction mixtures was 50, 25 and 5 microg mL(-1) for the initial concentration of 1000, 500 and 100 microg mL(-1), respectively. They showed concentration-dependent inhibition of mushroom tyrosinase. Those extracts expressing relatively weak tyrosinase inhibitory activity may act through different inhibition pathway which is not based on tyrosinase activity. Further evaluation of the most potent tyrosinase inhibitors in in vivo conditions would be recommended.

Publication Types: PMID: 18822041 [PubMed - indexed for MEDLINE]

11. An in vitro investigation of herbs traditionally used for kidney and urinary system disorders: Potential therapeutic and toxic effects.

Wojcikowski K, Wohlmuth H, Johnson DW, Rolfe M, Gobe G.

Molecular and Cellular Pathology, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

Aim: Renal fibrosis is central to progression of most chronic renal pathologies. Antioxidants that protect the tubular epithelium and anti-fibrotics that induce apoptosis of pro-fibrotic myofibroblasts without adversely affecting tubular epithelium may slow progression of renal fibrosis, while toxic substances may exacerbate renal scarring. We investigated 47 herbs for their in vitro toxic or antioxidant effects on normal renal mammalian fibroblasts (NRK49F) and tubular epithelial cells (NRK52E) to determine their potential value as therapeutic agents in renal fibrosis involving oxidative stress. Methods: Herbs were chosen because of their traditional use in kidney or urinary system disorders, or because of recent published interest in their therapeutic or toxic potential in kidney disease. Extracts of herbs were made using a sequential multi-solvent extraction process. Each extract was analysed separately. Extraction solvents were ethyl acetate, methanol and 50% aqueous methanol. Cells were treated with extracts with/without oxidative stress (1.0 mM hydrogen peroxide). Cellular changes (apoptosis, necrosis, mitosis, transdifferentiation) were identified and quantified using defined criteria. Results: All extracts of Dioscorea villosa showed significant toxicity to both cell lines. At low concentrations (5-50 microg/mL) they induced epithelial to mesenchymal transdifferentiation, as demonstrated by increased immunohistochemistry staining for alpha-smooth muscle actin and transforming growth factor-beta1 in treated versus control cells. Angelica sinensis, Centella asiatica, Glycyrrhiza glabra, Scutellaria lateriflora, and Olea europaea demonstrated strong antioxidant effects in epithelial cells and/or apoptotic effects on fibroblasts. Conclusion: This investigation has revealed renotoxicity of D. villosa and anti-fibrotic, oxidant potential of several herbal extracts, all of which require further study.

PMID: 18808387 [PubMed - as supplied by publisher]

12. Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice).

Zhang Q, Ye M.

Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, No. 38 Xueyuan Road, Beijing 100191, China.

Gan-Cao, or licorice, is a popular Chinese herbal medicine derived from the dried roots and rhizomes of Glycyrrhiza uralensis, G. glabra, and G. inflata. The main bioactive constituents of licorice are triterpene saponins and various types of flavonoids. The contents of these compounds may vary in different licorice batches and thus affect the therapeutic effects. In order to ensure its efficacy and safety, sensitive and accurate methods for the qualitative and quantitative analyses of saponins and flavonoids are of significance for the comprehensive quality control of licorice. This review describes the progress in chemical analysis of licorice and its preparations since 2000. Newly established methods are summarized, including spectroscopy, thin-layer chromatography, gas chromatography, high-performance liquid chromatography (HPLC), liquid chromatography/mass spectrometry (LC/MS), capillary electrophoresis, high-speed counter-current chromatography (HSCCC), electrochemistry, and immunoassay. The sensitivity, selectivity and powerful separation capability of HPLC and CE allows the simultaneous detection of multiple compounds in licorice. LC/MS provides characteristic fragmentations for the rapid structural identification of licorice saponins and flavonoids. The combination of HPLC and LC/MS is currently the most powerful technique for the quality control of licorice.

PMID: 18703197 [PubMed - as supplied by publisher]

13. Production of glycyrrhizin in callus cultures of licorice.

Wongwicha W, Tanaka H, Shoyama Y, Tuvshintogtokh I, Putalun W.

Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.

Licorice plants, Glycyrrhiza glabra, G. uralensis, and G. inflata, were investigated for callus induction using Murashige and Skoog (MS) medium combined with auxins and cytokinins. After 4 weeks of culture, 33-100% of leaf or stem explants formed calli. Maximum of shoot induction from callus cultures was achieved by G. inflata stem explants cultured on MS medium supplemented with 1 mg/l alpha-naphthaleneacetic acid (NAA) and 0.5 mg/l 6-benzyladenine (BA) (67%) which also gave maximum shoot formation per explant (two shoots per explant). These results indicated that all three Glycyrrhiza species regenerated shoots from callus cultures on MS medium combined with NAA and BA or only thidiazuron (TDZ; 0.1 and 0.5 mg/l). Glycyrrhizin contents of G. uralensis calli induced using MS medium in combination with NAA and BA [(27.60 +/- 8.47) microg/g DW] or TDZ alone [(36.52 +/- 2.45) microg/ g DW] were higher than those found in other combinations.

Publication Types: PMID: 18669029 [PubMed - indexed for MEDLINE]


Genovese T, Menegazzi M, Mazzon E, Crisafulli C, Di Paola R, Dal Bosco M, Zou Z, Suzuki H, Cuzzocrea S.

*IRCCS Centro Neurolesi "Bonino-Pulejo", Messina; daggerBiochemistry Division, Department of Neuroscience and Vision, University of Verona; double daggerDepartment of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, Messina, Italy; and section signMinophagen Pharmaceutical Co., Ltd. Tokyo, Japan.

Glycyrrhizin, a major active constituent of liquorice root (Glycyrrhiza glabra), has a free radical scavenging property, and its effects were evaluated on an animal model of spinal cord injury (SCI) induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, tissue damage, and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated dUTP-biotin end labeling staining, Bax, and Bcl-2 expression). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine, iNOS, and poly(adenosine diphosphate-ribose) in the spinal cord tissue. Additionally, we demonstrate that these inflammatory events were associated with the activation of nuclear factor-kappaB. In contrast, the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) formation, (3) iNOS expression, (4) nuclear factor-kappaB activation, and (5) apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP-biotin end labeling, Bax, and Bcl-2) was markedly reduced in spinal cord tissue obtained from mice treated with glycyrrhizin extract (10 mg/kg, i.p., 30 min before and 1 and 6 h after SCI). In a separate set of experiments, we have clearly demonstrated that glycyrrhizin extract treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with glycyrrhizin extract reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

PMID: 18665052 [PubMed - as supplied by publisher]

15. Glycyrrhizin attenuates the development of carrageenan-induced lung injury in mice.

Menegazzi M, Di Paola R, Mazzon E, Genovese T, Crisafulli C, Dal Bosco M, Zou Z, Suzuki H, Cuzzocrea S.

Biochemistry Division, Department of Neuroscience and Vision, University of Verona, Verona, Italy.

Glycyrrhizin is a triterpene glycoside, a major active constituent of licorice (Glycyrrhiza glabra) root and numerous pharmacological effects like anti-inflammatory, anti-viral, anti-tumour and hepatoprotective activities has been attributed to it. In this study we evaluated the anti-inflammatory activities of glycyrrhizin in mice model of acute inflammation, carrageenan-induced pleurisy. We report here that glycyrrhizin (given at 10 mg/kg i.p. 5 min prior to carrageenan) exerts potent anti-inflammatory effects in this model. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity which contained a large number of neutrophils (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation (as determinated by thiobarbituric acid-reactant substances measurement) and increased production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). All these parameters were attenuated by glycyrrhizin. Furthermore, carrageenan induced an upregulation of the expression of intercellular cell adhesion molecule (ICAM-1), P-selectin, as well as an increase in the amounts of nitrotyrosine and poly(ADP-ribose) (PAR), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine and PAR was significantly reduced by glycyrrhizin. Additionally, we demonstrate that these inflammatory events were associated with the activation of nuclear factor-kappaB (NF-kappaB) and signal transducer and activator transcription-3 (STAT-3) activation in the lung. NF-kappaB and STAT-3 activation were significantly reduced by glycyrrhizin treatment. Taken together, our results indicate that prevention of the activation of NF-kappaB and STAT-3 by glycyrrhizin reduces the development of acute inflammation.

Publication Types: PMID: 18590825 [PubMed - indexed for MEDLINE]

16. Immunostimulating complexes incorporating Eimeria tenella antigens and plant saponins as effective delivery system for coccidia vaccine immunization.

Berezin VE, Bogoyavlenskiy AP, Tolmacheva VP, Makhmudova NR, Khudyakova SS, Levandovskaya SV, Omirtaeva ES, Zaitceva IA, Tustikbaeva GB, Ermakova OS, Aleksyuk PG, Barfield RC, Danforth HD, Fetterer RH.

Institute of Microbiology and Virology, Ministry of Education and Science of Kazakhstan, 103 Bogenbai Batyr Str., 480100 Almaty, Kazakhstan.

Immunostimulating complexes (ISCOMs) are unique, multimolecular structures formed by encapsulating antigens, lipids, and triterpene saponins of plant origin, and are an effective delivery system for various kinds of antigens. The uses of ISCOMs formulated with saponins from plants collected in Kazakhstan, with antigens from the poultry coccidian parasite Eimeria tenella, were evaluated for their potential use in developing a vaccine for control of avian coccidiosis. Saponins isolated from the plants Aesculus hippocastanum and Glycyrrhiza glabra were partially purified by HPLC. The saponin fractions obtained from HPLC were evaluated for toxicity in chickens and chicken embryos. The HPLC saponin fractions with the least toxicity, compared to a commercial saponin Quil A, were used to assemble ISCOMs. When chicks were immunized with ISCOMs prepared with saponins from Kazakhstan plants and E. tenella antigens, and then challenged with E. tenella oocysts, significant protection was conveyed compared to immunization with antigen alone. The results of this study indicate that ISCOMs formulated with saponins isolated from plants indigenous to Kazakhstan are an effective antigen delivery system which may be successfully used, with low toxicity, for preparation of highly immunogenic coccidia vaccine.

Publication Types:

PMID: 18564738 [PubMed - indexed for MEDLINE]

17. Medicinal plant treatments for fleas and ear problems of cats and dogs in British Columbia, Canada.

Lans C, Turner N, Khan T.

DVM, P.O. Box 72045, Sasamat, Vancouver, BC V6R4P2, Canada. cher2lans@netscape.net

Research conducted in 2003/2004 documented and validated (in a non-experimental way) ethnoveterinary medicines used by small-scale, organic livestock farmers in British Columbia (BC), Canada. Interviews were conducted with 60 participants who were organic farmers or holistic medicinal/veterinary practitioners. A workshop was held with selected participants to discuss the plant-based treatments. This paper reports on the medicinal plants used for fleas in cats and dogs. Fleas and flies are treated with Artemisia vulgaris L. (Asteraceae), Citrus x limon (L.), Juniperus communis L. var. depressa Pursh. (Cupressaceae), Lavandula officinalis L. (Labiatae), Melissa officinalis L. (Lamiaceae), and Thuja plicata Donn ex D. Don (Cupressaceae). All of the plants used have insecticidal activity. Ear problems are treated with Achillea millefolium L., Calendula officinalis L., and Helichrysum angustifolium (Roth.) G. Don. (Asteraceae), Allium sativum L. (Alliaceae), Berberis aquifolium Pursh./Mahonia aquifolium (Berberidaceae), Glycyrrhiza glabra L. (Fabaceae), Lobelia inflata L. (Campanulaceae), Matricaria recutita L., Melaleuca alternifolia L. (Myrtaceae), Origanum vulgare L. (Labiatae), Ricinus communis L. (Euphorbiaceae), Syzygium aromaticum (L.) Merr. & L. M. Perry (Myrtaceae), Thymus vulgaris L. (Lamiaceae), and Verbascum thapsus L. (Scrophulariaceae).

Publication Types: PMID: 18563443 [PubMed - indexed for MEDLINE]

18. Biological screening of 100 plant extracts for cosmetic use (I): inhibitory activities of tyrosinase and DOPA auto-oxidation.

Lee KT, Kim BJ, Kim JH, Heo MY, Kim HP.

College of Pharmacy, Kangwon National University, Chuncheon, Korea.

The aim of this study was to evaluate several plant extracts with a view to developing melanogenesis inhibitors. In this study, 100 plant extracts were screened to elucidate their whitening effects using in vitro inhibition of tyrosinase and DOPA auto-oxidation activity. Several plant extracts such as Chaenomeles speciosa, Dryopteris crassirhizoma, Gastrodia ellata, Glycyrrhiza glabra, Morus alba, Myristica fragrans, Rheum palmatum and Sophora japonica showed inhibition of mushroom tyrosinase activity. Plant extracts including Bupleurum falcatum, Caragana sinica, Morus alba and Tussilago farfara showed inhibition of DOPA auto-oxidation activity.

PMID: 18505483 [PubMed - in process]

19. Effect of glabridin from Glycyrrhiza glabra on learning and memory in mice.

Cui YM, Ao MZ, Li W, Yu LJ.

College of Life Science and Technology, Institute of Resource Biology and Biotechnology, Huazhong University of Science & Technology, Wuhan, P. R. China.

Glabridin was isolated from the roots of Glycyrrhiza glabra and its effects on cognitive functions and cholinesterase activity were investigated in mice. Glabridin (1, 2 and 4 mg kg (-1), P. O.) and piracetam (400 mg kg (-1), i. p.), a clinically used nootropic agent, were administered daily for 3 successive days to different groups of mice. The higher doses (2 and 4 mg kg (-1), P. O.) of glabridin and piracetam significantly antagonized the amnesia induced by scopolamine (0.5 mg kg (-1), I. P.) in both the elevated plus maze test and passive avoidance test. Furthermore, glabridin (2 and 4 mg kg (-1), P. O.) and metrifonate (50 mg kg (-1), I. P.), used as a standard drug, both remarkably reduced the brain cholinesterase activity in mice compared to the control group. Therefore, glabridin appears to be a promising candidate for memory improvement and it will be worthwhile to explore the potential of glabridin in the management of Alzheimer patients.

PMID: 18484526 [PubMed - indexed for MEDLINE]

20. Isoliquiritigenin, a flavonoid from licorice, relaxes guinea-pig tracheal smooth muscle in vitro and in vivo: role of cGMP/PKG pathway.

Liu B, Yang J, Wen Q, Li Y.

Department of Pharmacology, College of Medicine, Wuhan University, Wuhan 430071, China; Department of Pharmacy, Hubei Cancer Hospital, Wuhan 430079, China.

Licorice root is used to treat asthma as a component of Shaoyao-Gancao-tang, a traditional Chinese medicine formula. In this study, we investigated the tracheal relaxation effects of isoliquiritigenin, a flavonoid isolated from the roots of Glycyrrhiza glabra (a kind of Licorice), on guinea-pig tracheal smooth muscle in vitro and in vivo. The tension changes of isolated tracheal rings were isometrically recorded on a polygraph.The large-conductance Ca2+-activated K+ channels (BKCa) were measured by inside-out patch-clamp techniques and intracellular Ca2+concentrations ([Ca2+]i) were tested by microfluorometric method in guinea-pig tracheal smooth muscle cells (TSMCs). Isoliquiritigenin produced concentration-dependent relaxation in isolated guinea-pig tracheal rings precontracted with acetylcholine, KCl, and histamine. Pretreatments with charybdotoxin, ODQ and KT5823 attenuated the relaxation induced by isoliquiritigenin. Isoliquiritigenin significantly increased intracellular cGMP level in cultured TSMCs and inhibited the activity of phosphodiesterase (PDE) 5 in human platelets. Moreover, isoliquiritigenin increased by 9-fold the probability of BKCa channel openings of TSMCs in inside-out patches and markedly reduced [Ca2+]i rise induced by acetylcholine inTSMCs, pretreatment with KT5823 attenuated above two responses to isoliquiritigenin. In vivo experiment isoliquiritigenin significantly prolonged the latency time of histamine-acetylcholine aerosol-induced collapse and inhibited the increase of lung overflow induced by intravenously administered histamine dose-dependently. These data indicate that isoliquiritigenin relaxes guinea-pig trachea through a multiple of intracellular actions, including sGC activation, inhibition of PDEs, and associated activation of the cGMP/PKG signaling cascade, leading to the opening of BKCa channels and [Ca2+]i decrease through PKG-dependent mechanism and thus to tracheal relaxation.

Publication Types: PMID: 18462716 [PubMed - indexed for MEDLINE]

21. A time course analysis of systemic administration of aqueous licorice extract on spatial memory retention in rats.

Sharifzadeh M, Shamsa F, Shiran S, Karimfar MH, Miri AH, Jalalizadeh H, Gholizadeh S, Salar F, Tabrizian K.

Department of Toxicology-Pharmacology and Center of Excellence of Toxicology, Pharmaceutical Sciences and Medicinal Plants Research Centers, Faculty of Pharmacy, Tehran University of Medicinal Sciences, Tehran, Iran.

In the present study, the time course of the effects of Glycyrrhiza glabra L. (Leguminosae) aqueous extract (GE), administered systemically to rats, on the spatial memory retention in the Morris water maze was investigated. The dose of glycyrrhizin (GL), i. e., 0.5, 2.5 and 5 mg/mL in daily water intake of GE was administered to three groups of rats. The first, second and third groups received GE for 1, 2 and 4 weeks, respectively (each group included 3 subgroups). Three additional control groups of animals received only tap water during the same periods of time. After terminating the treatments, all animals were trained for four days; each day included one block and each block contained four trials. Test trials were conducted 48 h after the completion of the training period. Nicotine (1 microg/side) was infused into the CA1 region of the hippocampus as a positive drug control. GE treatment decreased both escape latency and traveled distance, but not swimming speed, compared with control, suggesting significant spatial memory retention enhancement by GE. Statistical analysis did not show any significant difference between GE-treated animals and the nicotine group in escape latency and traveled distance. At the end of the testing trials plasma samples were collected and the concentrations of glycyrrhetinic acid (GA) as a major metabolite of GL were measured in the different groups of treated rats. The maximum concentration was observed after four weeks of GE administration at 5 mg/mL of GL. These results showed that the enhancement effect of GE on spatial memory retention does not correlate with GA blood levels.

PMID: 18404595 [PubMed - indexed for MEDLINE]

22. Chinese herbal medicine (Tuhuai extract) exhibits topical anti-proliferative and anti-inflammatory activity in murine disease models.

Man MQ, Shi Y, Man M, Lee SH, Demerjian M, Chang S, Feingold KR, Elias PM.

Dalian Skin Disease Hospital, Liaoning, China.

While psoriasis is one of the most common skin disorders in humans, effective, safe and inexpensive treatments are still largely unavailable. Chinese herbal medicine (CHM) has been used for centuries for treating psoriasis and several reports claim that systemic administration of one such CHM, Tuhuai, mainly composed of flos sophorae, smilax glabra roxb and licorice, is effective in psoriasis. However, the mechanisms by which this CHM improves psoriasis are not yet clear. Two universal features of psoriasis are epidermal hyperplasia and inflammation. Moreover, drugs that specifically inhibit epidermal hyperplasia and/or inflammation are widely used to treat psoriasis. Here, we investigated whether topical applications of Tuhuai extract exhibit anti-proliferative and anti-inflammatory activities in two murine models of inflammatory dermatoses. To assess Tuhuai's potential anti-proliferative effect, we disrupted epidermal barrier function twice-daily for 4 days in normal hairless mice followed by topical applications of either 1% Tuhuai extract or Vehicle to both flanks immediately after each barrier perturbation. Changes in epidermal proliferation and apoptosis were evaluated by immunohistochemistry and TUNEL staining. To assess the anti-inflammatory effects of Tuhuai, both irritant (phorbol ester) and acute allergic contact dermatitis (oxazolone) models were used. Whereas topical Tuhuai extract did not alter epidermal proliferation or induce irritation in normal skin, it both reduced epidermal hyperplasia in the epidermal hyperproliferative model, and reduced inflammation in both irritant and allergic contact dermatitis models. As topical Tuhuai extract exhibits anti-proliferative and anti-inflammatory properties in a variety of human models of inflammatory dermatoses, Tuhuai could provide an effective, relatively safe and inexpensive therapeutic alternative for the treatment of inflammatory dermatoses, including psoriasis.

Publication Types: PMID: 18341576 [PubMed - indexed for MEDLINE]

23. Fungal contamination of raw materials of some herbal drugs and recommendation of Cinnamomum camphora oil as herbal fungitoxicant.

Singh P, Srivastava B, Kumar A, Dubey NK.

Centre of Advanced Study in Botany, Banaras Hindu University, Varanasi, 221005, India.

The paper explores fungal infection and aflatoxin B1 contamination of six medicinal plant samples viz. Adhatoda vasica Nees, Asparagus racemosus Linn., Evolvulus alsinoides Linn., Glycyrrhiza glabra Linn., Plumbago zeylanica Linn. and Terminalia chebula Retz. A total of 858 fungal isolates were detected from the raw materials. Maximum number of fungal isolates was detected from A. racemosus (228). The genus Aspergillus was found to be the most dominant genus causing infection to most of the raw materials. Among the 32 isolates of A. flavus tested, 13 isolates were found to be toxigenic elaborating aflatoxin B1. The highest elaboration of aflatoxin B1 was 394.95 ppb by the isolates of A. flavus from G. glabra. The essential oil of Cinnamomum camphora (L.) Presl showed efficacy in arresting aflatoxin B1 by the toxigenic strain. The growth of a toxigenic strain of A. flavus decreased progressively with increasing concentration of essential oil from leaves of C. camphora. The oil completely inhibited aflatoxin B1 production even at 750 ppm. Hence, the oil of C. camphora is recommended as herbal fungitoxicant against the fungal contamination of the raw materials.

Publication Types: PMID: 18322727 [PubMed - indexed for MEDLINE]

24. Antimicrobial potential of Glycyrrhiza glabra roots.

Gupta VK, Fatima A, Faridi U, Negi AS, Shanker K, Kumar JK, Rahuja N, Luqman S, Sisodia BS, Saikia D, Darokar MP, Khanuja SP.

Genetic Resources and Biotechnology Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.

The present study was aimed to investigate antimicrobial potential of Glycyrrhiza glabra roots. Antimycobacterial activity of Glycyrrhiza glabra was found at 500 microg/mL concentration. Bioactivity guided phytochemical analysis identified glabridin as potentially active against both Mycobacterium tuberculosis H(37)Ra and H(37)Rv strains at 29.16 microg/mL concentration. It exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. Our results indicate potential use of licorice as antitubercular agent through systemic experiments and sophisticated anti-TB assay.

Publication TypesPMID: 18182260 [PubMed - indexed for MEDLINE]

25. Mechanism of anti-inflammatory action of liquorice extract and glycyrrhizin.

Racková L, Jancinová V, Petríková M, Drábiková K, Nosál R, Stefek M, Kostálová D, Prónayová N, Kovácová M.

Institute of Experimental Pharmacology Slovak Academy of Sciences, Bratislava, Slovak Republic. exfadada@savba.sk

The antiradical activity, protective effect against lipid peroxidation of liposomal membrane, and inhibitory effect on whole blood reactive oxygen species (ROS) liberation of Glycyrrhiza glabra crude extract and glycyrrhizin, its major compound, were assessed. The liquorice extract showed significant activity in all the three assay systems used in a dose dependent manner. It displayed remarkable reactivity with free stable 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical, inhibitory efficacy in peroxidatively damaged unilamellar dioleoyl phosphatidylcholine (DOPC) liposomes, and inhibition of ROS chemiluminescence, generated by whole blood, induced by both receptor-bypassing stimuli (PMA) and receptor operating stimuli (Opz) in the ranking order of stimuli PMA> Opz. These activities may be attributed to phenolic antioxidants involving isoflavan derivatives, coumarins and chalcones. Nonetheless, triterpene saponin glycyrrhizin exhibited no efficacy in the system of DPPH reaction and peroxidation of liposomal membrane, and negligible inhibition of chemiluminescence generated by inflammatory cells. These results indicate that the mechanism of anti-inflammatory effect of glycyrrhizin most probably does not involve ROS and this major constituent is not responsible for the inhibition effects of liquorice extract on neutrophil functions.

Publication Types:

PMID: 18075885 [PubMed - indexed for MEDLINE]

26. In vitro and in vivo neuroprotective effect and mechanisms of glabridin, a major active isoflavan from Glycyrrhiza glabra (licorice).

Yu XQ, Xue CC, Zhou ZW, Li CG, Du YM, Liang J, Zhou SF.

Department of Nephrology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Stroke is a life-threatening disease characterized by rapidly developing clinical signs of focal or global disturbance of cerebral function due to cerebral ischemia. A number of flavonoids have been shown to attenuate the cerebral injuries in stroked animal models. Glabridin, a major flavonoid of Glycyrrhiza glabra (licorice), possesses multiple pharmacological activities. This study aimed to investigate whether glabridin modulated the cerebral injuries induced by middle cerebral artery occlusion (MCAO) in rats and staurosporine-induced damage in cultured rat cortical neurons and the possible mechanisms involved. Our study showed that glabridin at 25mg/kg by intraperitoneal injection, but not at 5mg/kg, significantly decreased the focal infarct volume, cerebral histological damage and apoptosis in MCAO rats compared to sham-operated rats. Glabridin significantly attenuated the level of brain malonyldialdehyde (MDA) in MCAO rats, while it elevated the level of two endogenous antioxidants in the brain, i.e. superoxide dismutase (SOD) and reduced glutathione (GSH). Co-treatment with glabridin significantly inhibited the staurosporine-induced cytotoxicity and apoptosis of cultured rat cortical neurons in a concentration-dependent manner. Consistently, glabridin significantly reduced the DNA laddering caused by staurosporine in a concentration-dependent manner. Glabridin also suppressed the elevated Bax protein and caspase-3 proenzyme and decreased bcl-2 induced by staurosporine in cultured rat cortical neurons, facilitating cell survival. Glabridin also inhibited superoxide production in cultured cortical neurons exposed to staurosporine. These findings indicated that glabridin had a neuroprotective effect via modulation of multiple pathways associated with apoptosis. Further studies are warranted to further investigate the biochemical mechanisms for the protective effect of glabridin on neurons and the evidence for clinical use of licorice in the management of cerebral ischemia.

Publication Types: PMID: 18048062 [PubMed - indexed for MEDLINE]

27. [Changes of morphological indicators of blood from vibration and liquorice effect]

[Article in Russian]

Minasian SM, Adamian TsI, Gevorkian ES.

The effect of long-term exposure of vibration and feeding rabbits with liquorice (Glycyrrhiza glabra L) on peripheral blood indicators was studied. It was found that biological active substances of licorice accelerate metabolism processes of the marrow stem cells, enlarge organism compensatory abilities, in that way providing organism resistance to vibration.

Publication Types: PMID: 18030801 [PubMed - indexed for MEDLINE
28. Effect of Fagonia Arabica (Dhamasa) on in vitro thrombolysis.

Prasad S, Kashyap RS, Deopujari JY, Purohit HJ, Taori GM, Daginawala HF.

Biochemistry Research Laboratory, Central India Institute of Medical Sciences, 88/2, Bajaj Nagar, Nagpur-440010, Maharashtra, India. sweta_ciims@yahoo.com

BACKGROUND: Atherothrombotic diseases such as myocardial or cerebral infarction are serious consequences of the thrombus formed in blood vessels. Thrombolytic agents are used to dissolve the already formed clots in the blood vessels; however, these drugs have certain limitations which cause serious and sometimes fatal consequences. Herbal preparations have been used since ancient times for the treatment of several diseases. Herbs and their components possessing antithrombotic activity have been reported before; however, herbs that could be used for thrombolysis has not been reported so far. This study's aim was to investigate whether herbal preparations (aqueous extract) possess thrombolytic activity or not. METHODS: An in vitro thrombolytic model was used to check the clot lysis effect of six aqueous herbal extracts viz., Tinospora cordifolia, Rubia cordifolia, Hemidesmus indicus, Glycyrrhiza glabra Linn, Fagonia Arabica and Bacopa monnieri Linn along with Streptokinase as a positive control and water as a negative control. RESULTS: Using an in vitro thrombolytic model, Tinospora cordifolia, Rubia cordifolia, Hemidesmus indicus, Glycyrrhiza glabra Linn, Fagonia Arabica and Bacopa monnieri Linn showed 19.3%, 14.5%, 20.3%, 17.8%, 75.6% and 41.8% clot lysis respectively . Among the herbs studied Fagonia arabica showed significant % of clot lysis (75.6%) with reference to Streptokinase (86.2%). CONCLUSION: Through our study it was found that Dhamasa possesses thrombolytic properties that could lyse blood clots in vitro; however, in vivo clot dissolving properties and active component(s) of Dhamasa for clot lysis are yet to be discovered. Once found Dhamasa could be incorporated as a thrombolytic agent for the improvement of patients suffering from Atherothrombotic diseases.

Publication Types: PMID: 17986325 [PubMed - indexed for MEDLINE] PMCID: PMC2213682

29. Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice.

Lee CH, Park SW, Kim YS, Kang SS, Kim JA, Lee SH, Lee SM.

College of Pharmacy, Sungkyunkwan University, Gyeonggi-do, Korea.

Glycyrrhizin is the major active component extracted from licorice (Glycyrrhiza glabra) roots, one of the most widely used herbal preparations for the treatment of liver disorders. This study evaluated the potential beneficial effect of glycyrrhizin in a mouse model of carbon tetrachloride (CCl(4))-induced liver injury. The mice were treated intraperitoneally with CCl(4) (0.5 ml/kg). They received glycyrrhizin (50, 100, 200, 400 mg/kg) 24 h and 0.5 h before and 4 h after administering CCl(4). The serum activities of aminotransferase and the hepatic level of malondialdehyde were significantly higher 24 h after the CCl(4) treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by glycyrrhizin. CCl(4) increased the level of circulating tumor necrosis factor-alpha markedly, which was reduced by glycyrrhizin. The levels of hepatic inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 protein expression were markedly higher after the CCl(4) treatment. Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin. CCl(4) increased the level of tumor necrosis factor-alpha, inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 mRNA expressions. The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions. These results suggest that glycyrrhizin alleviates CCl(4)-induced liver injury, and this protection is likely due to the induction of heme oxygenase-1 and the downregulation of proinflammatory mediators.

Publication Types: PMID: 17917259 [PubMed - indexed for MEDLINE]

30. Antiviral effects of Glycyrrhiza species.

Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J.

Department of Medical and Surgical Sciences-Endocrinology, University of Padua, Padova, Italy.

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus-induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus. Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency. Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs.

Publication Types: PMID: 17886224 [PubMed - indexed for MEDLINE]

31. Antifibrotic effects of a herbal combination regimen on hepatic fibrotic rats.

Lin YL, Hsu YC, Chiu YT, Huang YT.

National Research Institute of Chinese Medicine, Taipei, Taiwan.

Liver fibrosis has been characterized as chronic inflammatory processes involving multiple molecular pathogenetic pathways. This therapeutic study investigated whether a combination regimen of Salvia miltiorrhiza (S), Ligusticum chuanxiong (L) and Glycyrrhiza glabra (G) exerted in vivo antifibrotic effects on rats with hepatic fibrosis. Fibrosis was induced in rats by dimethylnitrosamine (DMN) administration for 4 weeks. Fibrotic rats were randomly assigned to one of the three groups: control, SLG (50 mg/kg) or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting 1 week after DMN injection. The results showed that fibrosis scores of livers from DMN-treated rats with SLG (1.13 +/- 0.13) were significantly reduced in comparison with DMN-treated rats receiving vehicle (1.63 +/- 0.18). Moreover, the hepatic collagen content of DMN rats was significantly reduced by either SLG or silymarin treatment. The double immunohistochemical staining results also showed that alpha-SMA positive cells with NF kappa B nuclear translocation were decreased in the fibrotic livers by SLG and silymarin treatments. The mRNA expression levels of TGF-beta1, alpha-SMA, collagen1 alpha 2, iNOS and ICAM-1 genes were attenuated by SLG and silymarin treatment. The results showed that SLG exerted antifibrotic effects in rats with DMN-induced hepatic fibrosis.

Publication Types: PMID: 17724770 [PubMed - indexed for MEDLINE]

32. Modulatory effect of spice extracts on iron-induced lipid peroxidation in rat liver.

Yadav AS, Bhatnagar D.

School of Biochemistry, Devi Ahilya University, Khandwa Road, Indore 452017, India.

The antioxidants in foods play an important role in preventing the generation of reactive oxygen species (ROS). Some of the dietary constituents, commonly used in Indian foods such as cloves (Syzygium aromaticum), licorice (Glycyrrhiza glabra), mace (aril of Myristica fragrans) and greater cardamom (Amomum subulatum), were selected as the test samples to find their effect on the inhibition of lipid peroxidation (LPO) in rat liver homogenate. Three different oxidant systems were used to induce LPO. The results show that all the spices have antioxidant activities at various concentrations. None of the spices showed prooxidant properties. The effect of spices on the inhibition of LPO was concentration dependent. Cloves, mace and cardamom inhibited the initiation as well as propagation phases of FeCl_{3} induced LPO, while licorice inhibited the initiation phase only. The reducing power and the superoxide scavenging activity of spices was also measured in vitro. The reducing power of various spices increased with concentration. The percentage inhibition of superoxide radical generation by the spices was also observed to be concentration dependent. The results show that spices used in the present study have significant ability to inhibit LPO due to their polyphenol content, strong reducing power and superoxide radical scavenging activity. Cloves showed the highest antioxidant activity probably due to the higher polyphenol content as compared to other spices.

PMID: 17673831 [PubMed - indexed for MEDLINE]

33. Species identification of licorice using nrDNA and cpDNA genetic markers.

Kondo K, Shiba M, Yamaji H, Morota T, Zhengmin C, Huixia P, Shoyama Y.

Botanical Raw Materials Research Department, Tsumura & Co., Ibaraki 300-1192, Japan. kondou_kenji@mail.tsumura.co.jp

For the accurate identification of medicinal licorice species, nucleotide sequences of four types of DNA regions were researched for 205 specimens, including three species used as licorice: Glycyrrhiza uralensis, Glycyrrhiza glabra, and Glycyrrhiza inflata. The four DNA regions were the internal transcribed spacer (ITS) on nuclear ribosomal DNA, the rbcL gene, the matK gene, and the trnH-psbA intergenic region on chloroplast DNA (cpDNA). Ten genotypes were consequently recognized as combinations of the sequence data obtained from the four DNA regions. Species-specific genotypes were defined from the frequency of the appearance of species in each genotype and from the phylogenetic relationships of the 10 genotypes. This revealed the possibility of identifying licorice species based on the 10 genotypes. Next, comparison of species identifications by each DNA region suggested that efficient identification of licorice species is possible using the genetic information obtained from the ITS and trnH-psbA intergenic region. Additionally, concerning the phylogenetic relationships of the Glycyrrhiza species used as licorice, it is suggested from the genetic information of the four types of DNA regions that G. glabra is more closely related to G. inflata than to G. uralensis. In the G. uralensis examined, four genotypes were recognized as intra specific variations. The appearance frequency of each genotype in G. uralensis differed according to the area in China. G. uralensis may have expanded its distribution areas from western to eastern China because many licorices with the phylogenetic ancestral genotype were observed in western areas, while many with the derivative genotype were observed in eastern areas.

PMID: 17666810 [PubMed - indexed for MEDLINE]

34. Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root.

Dong S, Inoue A, Zhu Y, Tanji M, Kiyama R.

Signaling Molecules Research Laboratory, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan.

Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to that by E(2), whereas glycyrrhizin had no effect. Furthermore, the expression profile examined by cDNA microarray assay using a set of 120 estrogen-responsive genes, which were related to proliferation, transcription, transport, enzymes and signaling, showed a statistically significant correlation (R=0.47, P<0.0001) between the profiles for E(2) and the extract. However, the expression profile for glycyrrhizin was different from that of the extract and E(2). The results indicate that rapid signaling pathways, including Erk1/2 and Akt, and the subsequent transcriptional regulation are involved in the proliferation of MCF-7 cells induced by the extract of G. glabra root. Furthermore, the extract had estrogenic activity and a distinguishable profile of gene expression, suggesting the presence of potentially useful components other than glycyrrhizin in G. glabra root for hormone and anti-cancer therapies.

PMID: 17664038 [PubMed - indexed for MEDLINE]

35. The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD25 expression in humans: a pilot study.

Zwickey H, Brush J, Iacullo CM, Connelly E, Gregory WL, Soumyanath A, Buresh R.

Helfgott Research Institute, National College of Natural Medicine, Portland, OR 97201, USA. hzwickey@ncnm.edu

This phase 0, double-blind, repeated within subject, randomized pilot study examined CD25 expression on T cells after ingestion of three commonly used herbs: Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra, administered singly and in combination. CD25 expression on T cells was significantly increased for subjects ingesting Echinacea at 24 h with notable increases in activation from Astragalus and Glycyrrhiza. CD25 expression remains elevated with daily use of Echinacea for at least 7 days. Copyright (c) 2007 John Wiley & Sons, Ltd.

Publication Types: PMID: 17661330 [PubMed - indexed for MEDLINE]

36. Large molecules as anti-adhesive compounds against pathogens.

Wittschier N, Lengsfeld C, Vorthems S, Stratmann U, Ernst JF, Verspohl EJ, Hensel A.

University of Münster, Institute for Pharmaceutical Biology and Phytochemistry, Hittorfstrasse 56, D-48149 Münster, Germany.

Anti-adhesive compounds are potential prophylactic tools in alternative treatment regimes against bacterial infection, as bacterial adhesion is commonly mediated by carbohydrate-protein interactions between surface adhesions of microorganisms and the host cell. The use of exogenous polyvalent, high-molecular carbohydrates and tannin-like plant-derived compounds should antagonize the adhesive interaction. A range of carbohydrates and carbohydrate- and proanthocyanidin-enriched plant extracts were screened for potential anti-adhesive effects against Helicobacter pylori, Campylobacter jejuni, Porphyromonas gingivalis and Candida albicans in different in-situ assays on primary tissue. The adhesion of H. pylori on human stomach tissue was effectively blocked by glucuronic acid-enriched polysaccharides from immature okra fruits (Abelmoschus esculentus). These compounds also had strong in-vitro effects against C. jejuni (inhibition up to 80%), but were ineffective in an in-vivo study in infected chicken broilers due to metabolism in the gastrointestinal system. Polysaccharides from Glycyrrhizia glabra, also enriched with glucuronic acid, showed strong anti-adhesive properties against H. pylori and P. gingivalis (inhibition 60-70%). Pelargonium sidoides extract, containing mainly polymeric proanthocyanidins, was effective against H. pylori in a dose-dependent manner. Due to the multifunctional adhesive strategy of C. albicans, no effective compounds were detected against this yeast. Structure-activity relationships are presented and the potential in-vivo use of carbohydrate-based anti-adhesives is discussed.

PMID: 17637170 [PubMed - indexed for MEDLINE]

37. Clinical safety of licorice flavonoid oil (LFO) and pharmacokinetics of glabridin in healthy humans.

Aoki F, Nakagawa K, Kitano M, Ikematsu H, Nakamura K, Yokota S, Tominaga Y, Arai N, Mae T.

Functional Food Ingredients Division, Kaneka Corporation, 1-8 Miyamae-machi, Takasago, Hyogo 676-8688, Japan. Fumiki.Aoki@kn.kaneka.co.jp

OBJECTIVE: Licorice flavonoids have various physiological activities such as abdominal fat-lowering, hypoglycemic and antioxidant effects. Licorice flavonoid oil (LFO: Kaneka Glavonoid Rich Oil) is a new dietary ingredient containing licorice flavonoids dissolved in medium-chain triglycerides (MCT). Glabridin is one of the bioactive flavonoids included specifically in licorice Glycyrrhiza glabra L. and is the most abundant flavonoid in LFO. In this study, we assessed the safety of LFO in healthy humans and determined the plasma concentration profile of glabridin as a marker compound. METHODS: A single-dose and two multiple-dose studies at low (300 mg), moderate (600 mg) and high (1200 mg) daily doses of LFO were carried out using a placebo-controlled single-blind design. In each study the safety of LFO and the pharmacokinetics of glabridin were assessed. RESULTS: Pharmacokinetic analysis in the single-dose study with healthy male subjects (n = 5) showed that glabridin was absorbed and reached the maximum concentration (Cmax) after approximately 4 h (Tmax), and then eliminated relatively slowly in a single phase with a T1/2 of approximately 10 h at all doses. The Cmax and AUC(0-24 h) increased almost linearly with dose. The multiple-dose studies with healthy male and female subjects for 1 week and 4 weeks suggested that plasma glabridin reached steady state levels within 2 weeks with a single daily administration of 300 to 1200 mg/day LFO. In these human studies at three dose levels, there were no clinically noteworthy changes in hematological or related biochemical parameters. All clinical events observed were mild and considered to be unrelated to LFO administration even after repeated administration for 4 weeks. CONCLUSION: These studies demonstrated that LFO is safe when administered once daily up to 1200 mg/day. This is the first report on the safety of licorice flavonoids in an oil preparation and the first report on the pharmacokinetics of glabridin in human subjects.

Publication Types: PMID: 17634165 [PubMed - indexed for MEDLINE]

38. Constituent properties of licorices derived from Glycyrrhiza uralensis, G. glabra, or G. inflata identified by genetic information.

Kondo K, Shiba M, Nakamura R, Morota T, Shoyama Y.

Botanical Raw Materials Research Dept., Tsumura & Co., Ibaraki, Japan. kondou_kenji@mail.tsumura.co.jp

Constituent properties of licorices derived from Glycyrrhiza uralensis, G. glabra, and G. inflata are revealed by comparing 117 of licorice identified using four genetic markers; internal tracscribed spacer (ITS) on nuclear ribosomal DNA, rbcL gene, matK gene, and trnH-trnK1 intergenic region on chloroplast DNA. Regarding six main constituents of licorice; glycyrrhizin, liquiritin, liquiritin apioside, isoliquiritin, isoliquiritin apioside, and liquiritigenin, the constituent property of G. glabra resembles to that of G. inflata. On the other hand, the constituent property of G. uralensis is not similar to that of G. glabra or G. inflata and is characterized by a wide content variation of the six constituents compared to those of G. glabra and/or G. inflata. The mean contents of liquiritin, isoliquiritin, or liquilitigenin in G. uralensis are significantly higher than those of G. glabra or G. inflata. Therefore, the licorice species should be selected depending on these constituent properties for the traditional Chinese medicines or the Japanese Kampo medicines. Additionally, glycycoumarin, glabridin, and licochalcone A were reconfirmed as the species-specific typical constituents of G. uralensis, G. glabra, and G. inflata respectively. Therefore, it is resulted that the determination of the three species-specific constituents may be useful for the species identification of licorice. However, since 6% of licorice examined and hybrids were exceptions to the rule, their genetic information is necessary for the accurate species identification of licorice.

PMID: 17603166 [PubMed - indexed for MEDLINE]

39. Role of P-glycoprotein in limiting the brain penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra.

Yu XY, Lin SG, Zhou ZW, Chen X, Liang J, Yu XQ, Chowbay B, Wen JY, Duan W, Chan E, Li XT, Cao J, Li CG, Xue CC, Zhou SF.

Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Provincial Cardiovascular Institute, Guangzhou, 510080, China. yuxycn@hotmail.com

PURPOSE: Glabridin is a major active constituent of Glycyrrhiza glabra which is commonly used in the treatment of cardiovascular and central nervous system (CNS) diseases. Recently, we have found that glabridin is a substrate of P-glycoprotein (PgP/MDR1). This study aimed to investigate the role of PgP in glabridin penetration across the blood-brain barrier (BBB) using several in vitro and in vivo models. MATERIALS AND METHODS: Cultured primary rat brain microvascular endothelial cells (RBMVECs) were used in the uptake, efflux and transcellular transport studies. A rat bilateral in situ brain perfusion model was used to investigate the brain distribution of glabridin. The brain and tissue distribution of glabridin in rats with or without coadministered verapamil or quinidine were examined with correction for the tissue residual blood. In addition, the brain distribution of glabridin in mdr1a(-/-) mice was compared with the wild-type mice. Glabridin in various biological matrices was determined by a validated liquid chromatography mass spectrometric method. RESULTS: The uptake and efflux of glabridin in cultured RBMVECs were ATP-dependent and significantly altered in the presence of a PgP or multi-drug resistance protein (Mrp1/2) inhibitor (e.g. verapamil or MK-571). A polarized transport of glabridin was found in RBMVEC monolayers with facilitated efflux from the abluminal (BL) to luminal (AP) side. Addition of a PgP or Mrp1/2 inhibitor in both luminal and abluminal sides attenuated the polarized transport across RBMVECs. In a bilateral in situ brain perfusion model, the uptake of glabridin into the cerebrum increased from 0.42 +/- 0.09% at 1 min to 9.27 +/- 1.69% (ml/100 g tissue) at 30 min and was significantly greater than that for sucrose. Co-perfusion of a PgP or Mrp1/2 inhibitor significantly increased the brain distribution of glabridin by 33.6-142.9%. The rat brain levels of glabridin were only about 27% of plasma levels when corrected by tissue residual blood and it was increased to up to 44% when verapamil or quinidine was coadministered. The area under the brain concentration-time curve (AUC) of glabridin in mdr1a(-/-) mice was 6.0-fold higher than the wild-type mice. CONCLUSIONS: These findings indicate that PgP limits the brain penetration of glabridin through the BBB and PgP may cause drug resistance to glabridin (licorice) therapy for CNS diseases and potential drug-glabridin interactions. However, further studies are needed to explore the role of other drug transporters (e.g. Mrp1-4) in restricting the brain penetration of glabridin.

Publication Types: PMID: 17551811 [PubMed - indexed for MEDLINE]

40. Anti-oxidant constituents of the roots and stolons of licorice (Glycyrrhiza glabra).

Chin YW, Jung HA, Liu Y, Su BN, Castoro JA, Keller WJ, Pereira MA, Kinghorn AD.

Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.

As part of a search for new cancer chemopreventive agents, a new chalcone derivative (1), a novel group of neolignan lipid esters (2), and seven known phenolic compounds (formononetin, glabridin, hemileiocarpin, hispaglabridin B, isoliquiritigenin, 4'-O-methylglabridin, and paratocarpin B) (3-9) were isolated from the roots and stolons of licorice (Glycyrrhiza glabra). The structures of compound 1 and the individual components of isolate 2 were elucidated using various spectroscopic and chemical methods. All isolates were tested in an authentic peroxynitrite anti-oxidant assay. Of these compounds, hispaglabridin B (6), isoliquiritigenin (7), and paratocarpin B (9) were found to be the most potent anti-oxidant agents. Furthermore, isoliquiritigenin (7) was demonstrated to prevent the incidence of 1,2-dimethylhydrazine-induced colon and lung tumors in mice when administered at a dose of 300 mg/kg.

Publication Types: PMID: 17516657 [PubMed - indexed for MEDLINE]

41. Chemoprofile and bioactivities of Taverniera cuneifolia (Roth) Arn.: a wild relative and possible substitute of Glycyrrhiza glabra L.

Zore GB, Winston UB, Surwase BS, Meshram NS, Sangle VD, Kulkarni SS, Mohan Karuppayil S

School of Life Sciences, SRTM University, Nanded, Maharashtra, India.

Chemoprofile of Taverniera cuneifolia (Roth) Arn. a wild relative of commercial licorice (Glycyrrhiza glabra L) is presented. Both T. cuneifolia and G. glabra L were found to be very similar phytochemically. At least eighteen chromatophores were found similar in both the plants including the sweetening principle, glycyrrhizin. The extracts of T. cuneifolia root, exhibited promising anti-inflammatory, anti-tumor, anti germ tube formation (in Candida albicans), protection from mutagen toxicity and cytotoxic activities comparable to that of G. glabra. In general, the results suggest that T. cuneifolia could be used as substitute of G. glabra.

Publication Types: PMID: 17350239 [PubMed - indexed for MEDLINE]

42. In vitro and in vivo antiallergic effects of Glycyrrhiza glabra and its components.

Shin YW, Bae EA, Lee B, Lee SH, Kim JA, Kim YS, Kim DH.

College of Pharmacy, Kyung Hee University, Dongdaemun-ku, Seoul, Korea.

Licorice (Glycyrrhiza glabra L., Leguminosae) is frequently used in traditional medicine to treat inflammatory and allergic diseases. In this study, the main components (glycyrrhizin, 18beta-glycyrrhetinic acid, isoliquiritin, and liquiritigenin) were isolated from licorice, and their anti-allergic effects, such as antiscratching behavior and IgE production-inhibitory activity, were evaluated both in vitro and in vivo. Liquiritigenin and 18beta-glycyrrhetinic acid most potently inhibited the degranulation of RBL-2H3 cells induced by IgE with the antigen (DNP-HSA) and rat peritoneal mast cells induced by compound 48/80. Liquiritigenin and 18beta-glycyrrhetinic acid potently inhibited the passive cutaneous anaphylactic reaction as well as the scratching behavior in mice induced by compound 48/80. These components inhibited the production of IgE in ovalbumin-induced asthma mice but liquiritigenin had little effect. This suggests that the antiallergic effects of licorice are mainly due to glycyrrhizin, 18beta-glycyrrhetinic acid, and liquiritigenin, which can relieve IgE-induced allergic diseases such as dermatitis and asthma.

Publication Types: PMID: 17327992 [PubMed - indexed for MEDLINE]

43.Antioxidant capacity of 55 medicinal herbs traditionally used to treat the urinary system: a comparison using a sequential three-solvent extraction process.

Wojcikowski K, Stevenson L, Leach D, Wohlmuth H, Gobe G.

Molecular and Cellular Pathology, School of Medicine, University of Queensland, Brisbane, Queensland, Australia. kwojciko@scu.edu.au

BACKGROUND: The prevalence of chronic renal disease exceeds 10% in industrialized societies. Oxidative damage is thought to be one of the main mechanisms involved in nearly all chronic renal pathologies. OBJECTIVE: We aimed to use the oxygen radical absorbance capacity (ORAC) method and a sequential multisolvent extraction process to compare the in vitro antioxidant capacity of 55 medicinal herbs and prioritize them for in vivo studies investigating the value of herbal therapies in the treatment of renal disorders. METHODS: The herbs were chosen on the basis of their traditional use in kidney or urinary system disorders, or because they have attracted the attention of recent investigations into renal pathologies. The three solvents used for extraction were ethyl acetate, methanol, and 50% aqueous methanol. Silybum marianum (milk thistle) seed and Camellia sinensis (tea) leaf, both known to possess high antioxidant capacity, were included for comparison. RESULTS: Twelve of the 55 herbs were comparable to or exceeded ORAC levels of milk thistle seed or tea leaf. The highest radical-scavenging activity was found in Olea europaea (olive leaf), Cimicifuga racemosa (black cohosh), Rheum palmatum (rhubarb), Glycyrrhiza glabra (licorice), and Scutellaria lateriflora (Virginia skullcap). CONCLUSIONS: The antioxidant capacity of many of the herbs studied may, at least in part, be responsible for their reputation as being protective of organs of the urinary system. Overall, the combined ORAC values for the methanol and aqueous methanol extracts comprised 84% of the total ORAC value. Sequential extraction with solvents of different polarities may be necessary to fully extract the antioxidant principles from medicinal plants.

Publication Types: PMID: 17309384 [PubMed - indexed for MEDLINE]

44. Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra.

Cao J, Chen X, Liang J, Yu XQ, Xu AL, Chan E, Wei D, Huang M, Wen JY, Yu XY, Li XT, Sheu FS, Zhou SF.

Department of Pharmacy, School of Life Sciences, Queensland University of Technology, 2 George Street, Brisbane, Queensland 4001 Australia.

Glabridin is a major constituent of the root of Glycyrrhiza glabra, which is commonly used in the treatment of cardiovascular and central nervous system diseases. This study aimed to investigate the role of P-glycoprotein (PgP/MDR1) in the intestinal absorption of glabridin. The systemic bioavailability of glabridin was approximately 7.5% in rats, but increased when combined with verapamil. In single-pass perfused rat ileum with mesenteric vein cannulation, the permeability coefficient of glabridin based on drug disappearance in luminal perfusates (P(lumen)) was approximately 7-fold higher than that based on drug appearance in the blood (P(blood)). Glabridin was mainly metabolized by glucuronidation, and the metabolic capacity of intestine microsomes was 1/15 to 1/20 of that in liver microsomes. Polarized transport of glabridin was found in Caco-2 and MDCKII monolayers. Addition of verapamil in both apical (AP) and basolateral (BL) sides abolished the polarized transport of glabridin across Caco-2 cells. Incubation of verapamil significantly altered the intracellular accumulation and efflux of glabridin in Caco-2 cells. The transport of glabridin in the BL-AP direction was significantly higher in MDCKII cells overexpressing PgP/MDR1 than in the control cells. Glabridin inhibited PgP-mediated transport of digoxin with an IC(50) value of 2.56 microM, but stimulated PgP/MDR1 ATPase activity with a K(m) of 25.1 microM. The plasma AUC(0-24h) of glabridin in mdr1a(-/-) mice was 3.8-fold higher than that in wild-type mice. These findings indicate that glabridin is a substrate for PgP and that both PgP/MDR1-mediated efflux and first-pass metabolism contribute to the low oral bioavailability of glabridin.

Publication Types: PMID: 17220245 [PubMed - indexed for MEDLINE]

45. Hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (Linn) in rats.

Visavadiya NP, Narasimhacharya AV.

Department of Biosciences, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India.

The hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (GG) root powder were examined in hypercholesterolaemic male albino rats. A 4-week administration of GG root powder (5 and 10 gm% in diet) to hypercholesterolaemic rats resulted in significant reduction in plasma, hepatic total lipids, cholesterol, triglycerides and plasma low-density lipoprotein and VLDL-cholesterol accompanied by significant increases in HDL-cholesterol levels. Furthermore, significant increases in fecal cholesterol, neutral sterols and bile acid excretion along with an increase in hepatic HMG-CoA reductase activity and bile acid production were observed in these animals. The root powder administration to hypercholesterolaemic rats also decreased hepatic lipid peroxidation with a concomitant increase in superoxide dismutase (SOD) and catalase activities and total ascorbic acid content. Thus, the hypocholesterolaemic and antioxidant effects of GG root appeared to be mediated via (i) accelerated cholesterol, neutral sterol and bile acid elimination through fecal matter with an increased hepatic bile acid production and (ii) improving the activities of hepatic SOD, catalase and increasing the ascorbic acid content. The normo-cholesterolaemic animals when fed with GG root powder at 10 gm% level, registered a significant decline in plasma lipid profiles and an increase in HDL-cholesterol content. The antioxidant status of these animals also was improved upon treatment.

Publication Types: PMID: 17054099 [PubMed - indexed for MEDLINE]

46. A young female with quadriparesis.

Mukherjee T, Bhatt K, Sirsat R.

Section of Nephrology, PD Hinduja National Hospital and Medical Research Centre, Mahim, Mumbai 400 016.

We report a case of a young female who presented with acute onset quadriparesis secondary to severe hypokalemia. She was normotensive and had no metabolic alkalosis or kaliuresis. Serum potassium was corrected over the next few days and the quadriparesis resolved completely. A detailed history later on revealed that she had been consuming alternative medication for infertility for a prolonged duration and had discontinued it a month prior. One of the ingredients of this medicine was Glycyrrhiza glabra.

Publication Types: PMID: 16909739 [PubMed - indexed for MEDLINE]

47. Glycyrrhizin alleviates experimental allergic asthma in mice.

Ram A, Mabalirajan U, Das M, Bhattacharya I, Dinda AK, Gangal SV, Ghosh B.

Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.

Asthma is a chronic respiratory disease, the incidence of which is increasing globally. The existing therapy is inadequate and has many adverse effects. It needs a better therapeutic molecule preferably of natural origin, which has negligible or no adverse effects. In view of this, we evaluated Glycyrrhizin (GRZ), a major constituent of a plant Glycyrrhiza glabra, for its efficacy on asthmatic features in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to develop the asthmatic features such as airway hyperresponsiveness: allergen induced airway constriction and airway hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation. The mice were orally treated with GRZ (2.5, 5, 10 and 20 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect, respectively on the above asthmatic features. The status of airway hyperresponsiveness was measured by monitoring specific airway conductance (SGaw) using a non-invasive method and the pulmonary inflammation was assessed by haematoxylin and eosin staining of lung sections. Several other parameters associated with asthma such as interleukin (IL)-4, IL-5 interferon-gamma (IFN-gamma), OVA-specific IgE, total IgG(2a) and cortisol were measured by ELISA. GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway constriction, AHR to MCh (p<0.01), lung inflammation, and infiltration of eosinophils in the peribronchial and perivascular areas. It prevented the reduction of IFN-gamma (p<0.02), and decreased IL-4 (p<0.05), IL-5 (p<0.05) and eosinophils (p<0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE levels (p<0.01) and prevented the reduction of total IgG(2a) (p<0.01) in serum. We have also showed that it has no effect on serum cortisol levels. Our results demonstrate that GRZ alleviates asthmatic features in mice and it could be useful towards developing a better therapeutic molecule in the future.
Publication Types: PMID: 16846841 [PubMed - indexed for MEDLINE]

48. Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice.

Dhingra D, Parle M, Kulkarni SK.

Pharmacology Division, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India. din_dhingra@rediffmail.com

The central cholinergic pathways play a prominent role in the learning and memory processes. Acetylcholinesterase is an enzyme that inactivates acetylcholine. The present study was undertaken to estimate the acetylcholinesterase- inhibiting activity of extracts of Glycyrrhiza glabra, Myristica fragrans seeds, and ascorbic acid and compare these values with a standard acetylcholinesterase-inhibiting drug, metrifonate. Aqueous extract of G. glabra (150 mg/kg p.o. for 7 successive days), n-hexane extract of M. fragrans seeds (5 mg/kg p.o. for 3 successive days), ascorbic acid (60 mg/kg i.p. for 3 successive days), and metrifonate (50 mg/kg i.p.) were administered to young male Swiss albino mice. Acetylcholinesterase enzyme was estimated in brains of mice. G. glabra, M. fragrans, ascorbic acid, and metrifonate significantly decreased acetylcholinesterase activity as compared with their respective vehicle-treated control groups.

Publication Types: PMID: 16822217 [PubMed - indexed for MEDLINE]

49. The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD69 expression and immune cell activation in humans.

Brush J, Mendenhall E, Guggenheim A, Chan T, Connelly E, Soumyanath A, Buresh R, Barrett R, Zwickey H.

Helfgott Research Institute, National College of Naturopathic Medicine, Portland, OR, USA.

The increasing use of medicinal herbs among the general public has piqued the need for scientific-based research to determine the mechanism of action of herbs administered orally in human subjects. The ability of three herbs, Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra, to activate immune cells in human subjects was assessed in this pilot study. The effect of these herbs when ingested for 7 days was measured both when administered singly, and in combination, using flow cytometry. The primary cell activation marker measured was CD69. The results demonstrate that Echinacea, Astragalus and Glycyrrhiza herbal tinctures stimulated immune cells as quantified by CD69 expression on CD4 and CD8 T cells. This activation took place within 24 h of ingestion, and continued for at least 7 days. In addition, these three herbs had an additive effect on CD69 expression when used in combination.

Publication Types: PMID: 16807880 [PubMed - indexed for MEDLINE]

50. Modulatory effects of several herbal extracts on avian peripheral blood cell immune responses.

Dorhoi A, Dobrean V, Zăhan M, Virag P.

Department of Infectious Diseases, Faculty of Veterinary Medicine, Cluj-Napoca, Romania. a_opris@email.ro

Standardized ethanol extracts of Allium sativum (garlic), Glycyrrhiza glabra (licorice), Plantago major (plantain) and Hippophae rhamnoides (sea buckthorn) were assessed for their effects on cellular immunity in laying hens. Birds (n = 25) had blood samples taken and both specific and non-specific immune cell responsiveness were evaluated by a leukocyte proliferation assay, carbon clearance test and SRBC phagocytosis in monocyte-derived macrophage cultures. Licorice and sea buckthorn (50 microg/mL) clearly enhanced the macrophage membrane function (p < 0.05 and p < 0.01, respectively). Dual effects on circulating phagocytes were revealed for plantain and sea buckthorn, while garlic at 200 microg/mL impaired the phagocytic capacity of blood cells. None of the tested extracts showed mitogenic properties, but high concentrations of sea buckthorn (400 microg/mL) inhibited leukocyte proliferation. Small concentrations (20 microg/mL) of licorice proved the co-mitogenic potential for both T and B avian lymphocytes (p < 0.05). Certain extracts definitely enhanced the fowl innate and/or specific cell immunity and may therefore improve host resistance in poultry. Considering the chicken as an important non-mammalian model that also serves as an available laboratory approach for some human diseases, herbs exerting immunomodulatory properties may find relevant clinical applications. Copyright 2006 John Wiley & Sons, Ltd.

PMID: 16619362 [PubMed - indexed for MEDLINE]

51. [Study on circumscription of medicinal licorice species based on molecular biology]

[Article in Chinese]

Liu CS, Wang PY, Wang WQ.

School of Pharmacology, Beijing University of Chinese Medicine, Beijing 100029, China.

OBJECTIVE: Elucidate the medicinal licorice species circumscription in order to develop licorice resources in China and select new cultivars. METHOD: PCR amplification, DNA sequencing and cladistic analysis. RESULT: Acquire the ITS sequences and phylogenetic tree of 8 licorice species. CONCLUSION: According to results Glycyrrhiza eurycarpa and G. glabra var. glandulosa should be combined into G. and G. glabra respectively and G. egladulosa is an independent species.

Publication Types: PMID: 16468366 [PubMed - indexed for MEDLINE]

52. Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats.

Zhan C, Yang J.

Department of Pharmacology, School of Medicine, Wuhan University, Donghu Road, Wuhan 430071, China.

Epidemiological studies indicate that the intake of flavonoids is inversely associated with risk of stroke, cardiovascular diseases and cancer. Isoliquiritigenin (ISL), a flavonoid constituent in the root of Glycyrrhiza glabra, is known to have vasorelaxant effect, antioxidant, anti-platelet, anti-tumor, anti-allergic, antiviral activities and estrogenic properties. However, there is no report on the effects of ISL in cerebral ischemia. Evidence demonstrate that the impaired energy metabolism and the excessive generation of reactive oxygen radicals (ROS) contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effects of ISL were investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia-reperfusion injury in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-pretreated group, and three ISL-pretreated groups (5, 10 and 20 mg kg(-1), i.g.). ISL were administered once a day, for 7 days prior to ischemia. The rats were subjected to 2 h right MCAO via the intraluminal filament technique and 22 h reperfusion. Pretreatment with ISL significantly reduced the cerebral infarct volume and edema and produced significant reduction in neurological deficits. In this study, in order to clarify the mechanism of ISL's protection against cerebral ischemia damage, cerebral energy metabolism, brain Na+K+ATPase activity, malondialdehyde (MDA) content and antioxidant enzyme activities were measured. ISL pretreatment increased the brain ATP content, energy charge (EC) and total adenine nucleotides (TAN) in a dose-dependent manner. The brain Na+K+ATPase activity was protected significantly by pretreatment of ISL for 7 days. Pretreatment with ISL significantly inhibited the increases of brain MDA content and prevented the activities of brain superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) from declines caused by cerebral ischemia-reperfusion. All these findings indicate that ISL has the protective potential against cerebral ischemia injury and its protective effects may be due to the amelioration of cerebral energy metabolism and its antioxidant property.

PMID: 16459097 [PubMed - indexed for MEDLINE]

53. Simultaneous HPLC analysis, with isocratic elution, of glycyrrhizin and glycyrrhetic acid in liquorice roots and confectionery products.

Sabbioni C, Ferranti A, Bugamelli F, Forti GC, Raggi MA.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Glycyrrhizin (1), the main active principle of Glycyrrhiza glabra (liquorice) roots, is extensively used in herbal medicines, in pharmaceutical preparations and confectionery products. A feasible and reliable method which allows the simultaneous analysis of 1 and its aglycone, 18beta-glycyrrhetic acid (2), by means of an isocratic HPLC procedure is described. The system uses a C8 column as the stationary phase, and a mixture of acetonitrile, methanol, water and glacial acetic acid as the mobile phase. Good linearity was found in the concentration ranges 1-50 and 0.05-2.50 microg/mL for 1 and 2, respectively. A simple and rapid sample pre-treatment, based on the extraction of the two analytes with a mixture of water and ethanol, was developed for the examination of liquorice confectionery products and root samples. The HPLC method was shown to be appropriate, in terms of precision and feasibility, for the quality control of the analytes in these matrices.

Publication Types: PMID: 16454473 [PubMed - indexed for MEDLINE]

54. Antidepressant-like activity of Glycyrrhiza glabra L. in mouse models of immobility tests.

Dhingra D, Sharma A.

Pharmacology Division, Department Pharmaceutical Sciences, Guru Jambheshwar University, Hisar-125001 (Haryana), India. din_dhingra@rediffmail.com

The present study was undertaken to investigate the effects of aqueous extract of Glycyrrhiza glabra L. (Family: Fabaceae), popularly known as liquorice, on depression in mice using forced swim test (FST) and tail suspension test (TST). The extract of G. glabra (75, 150, and 300 mg/kg) was administered orally for 7 successive days in separate groups of Swiss young male albino mice. The dose of 150 mg/kg of the extract significantly reduced the immobility times of mice in both FST and TST, without any significant effect on locomotor activity of mice. The efficacy of extract was found to be comparable to that of imipramine (15 mg/kg i.p.) and fluoxetine (20 mg/kg i.p.). Liquorice extract reversed reserpine-induced extension of immobility period of mice in FST and TST. Sulpiride (50 mg/kg i.p.; a selective D2 receptor antagonist) and prazosin (62.5 microg/kg i.p.; an alpha1-adrenoceptor antagonist) significantly attenuated the extract-induced antidepressant-like effect in TST. On the other hand, p-chlorophenylalanine (100 mg/kg i.p.; an inhibitor of serotonin synthesis) did not reverse antidepressant-like effect of liquorice extract. This suggests that antidepressant-like effect of liquorice extract seems to be mediated by increase of brain norepinephrine and dopamine, but not by increase of serotonin. Monoamine oxidase inhibiting effect of liquorice may be contributing favorably to the antidepressant-like activity. Thus, it is concluded that liquorice extract may possess an antidepressant-like effect.

Publication Types: PMID: 16443316 [PubMed - indexed for MEDLINE]

55. Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra.

Sheela ML, Ramakrishna MK, Salimath BP.

Department of studies in Applied Botany and Biotechnology, University of Mysore, Manasagangothri, Mysore-570 006, India.

Blood vessel plays a crucial role in solid tumor development. It has been suggested that blocking of angiogenesis and the action of the cytokine VEGF could be possible in cancer therapy. In a screen for naturally occurring angiogenic inhibitors, we have identified an extract from the roots of Glycyrrhiza glabra, which has potent antiangiogenic and antitumor activity. The aqueous extract inhibits the in vivo and in vitro proliferation of Ehrlich ascites tumor cells. The angioinhibitory activity of G. glabra was confirmed by its inhibition of angiogenesis in in vivo assays, peritoneal and chorioallantoic membrane assay. Reduction in the levels of the cytokine VEGF and microvessel density count in the peritoneum of mice treated with G. glabra indicated that the plant extract decreased VEGF production and the cytokine induced neovascularization. Our results suggest that the extract from the roots of G. glabra may be a potential supplemental source for cancer therapy.

Publication Types: PMID: 16428085 [PubMed - in process]

56. Chemopreventive properties of the ethanol extract of chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells.

Jo EH, Kim SH, Ra JC, Kim SR, Cho SD, Jung JW, Yang SR, Park JS, Hwang JW, Aruoma OI, Kim TY, Lee YS, Kang KS.

Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, San 56-1, Shillim-Dong, Kwanak-gu, Seoul 151-742, South Korea.

Much of the interest on the chemopreventive properties of licorice has been focused on the plant genius Glycyrrhiza glabra. In this study the ethanol extract of Chinese licorice root, Glycyrrhiza uralensis (G. uralensis) was investigated for its estrogenic effect and the ability to inhibit cell proliferation in the MCF-7 human breast cancer cell line. The extract of the root of G. uralensis was fractionated in EtOH:H(2)O (80:20) (80% ethanol). The extract exhibited estrogenic effects similar to 17beta- estradiol (E2) and induced apoptosis at the same dose level (100 microg/ml) in MCF-7 breast cancer cells, results were associated with up-regulation of tumor suppressor gene p53 and pro-apoptotic protein Bax. G. uralensis extract caused the up-regulation of p21(waf1/cip1) and down-regulation of cdk 2 and cyclin E and most significantly, induced G1 cell cycle arrest. This is the first study to show that the ethanolic extract of the root of G. uralensis has an estrogen-like activity and anti-cancer effects against MCF-7 human breast cancer cells. Whilst the use of phytoestrogens to protect against hormone-dependent cancers or as a 'natural' alternative to hormone replacement therapy remains controversial, the data in this paper support the suggestion that extracts of root of the Chinese licorice G. uralensis might be of importance in this debate.

Publication Types: PMID: 16297710 [PubMed - indexed for MEDLINE]

57. Effect of licorice root on peripheral blood indexes upon vibration exposure.

Adamyan TI, Gevorkyan ES, Minasyan SM, Oganesyan KR, Kirakosyan KA.

Department of Human and Animal Physiology, Erevan State University, Erevan. anatom@ysu.am

We studied the effect of continuous vibration and treatment with licorice root (Glycyrrhiza glabra L.) on peripheral blood red cells in rabbits. Active substances of licorice root accelerated metabolism in cells of the bone marrow erythroid stem, enhanced compensatory reserve of the organism, and increased animal's resistance to stress.

PMID: 16283000 [PubMed - indexed for MEDLINE]

58. Application of microemulsion thin layer chromatography for the fingerprinting of licorice (Glycyrrhiza spp.).

Cui S, Fu B, Lee FS, Wang X.

The Key Laboratory of Analytical Science of MOE, The College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.

Microemulsion thin layer chromatography (ME-TLC) has been developed for the fingerprinting of aqueous extract of licorice (Glycyrrhiza spp.). The separation conditions and operational processes of the method have been optimized, and its chromatographic characteristics compared with conventional TLC. The ME-TLC system is easier to operate, and with higher resolution and better reproducibility than the conventional TLC. The separation mechanism and retention behavior of ME-TLC are found to differ significantly from conventional TLC. The technique has been applied to the analysis of different licorice species including G. uralensis, G. glabra and G. inflata; and to monitor the dynamic accumulation of active ingredients in licorice plant harvested at different times during its growing cycle in a Good Agriculture Practice (GAP) research farm. Results show that without post-chromatographic derivatization, the ME-TLC fingerprinting images of different species appear as clear, well resolved bands and with strong intensities to reveal distinctively different compositional features of the samples. The technique has also been applied successfully to monitor the dynamic accumulation of active components in licorice plant as a function of growing time in an experimental licorice farm. The study demonstrates the potential of ME-TLC technique as a rapid fingerprinting tool for the authentication and quality assessment of licorice as well as other herbs.

Publication Types: PMID: 16275172 [PubMed - indexed for MEDLINE]

59. Antifungal activity of plant extracts against Arthrinium sacchari and Chaetomium funicola.

Sato J, Goto K, Nanjo F, Kawai S, Murata K.

Quality Assurance, Coca-Cola (Japan) Company, Limited, 6-3 Shibuya 4-chome, Shibuya-ku, Tokyo 150-0002, Japan.

Various plant extracts were examined for antifungal activity with the objective of improving the commercial sterility of aseptically filled tea beverage products in PET bottles. When the hot water extract and the methanol extract of 29 samples were measured for their antifungal activity against Arthrinium sacchari M001 and Chaetomium funicola M002 strains, five samples, Acer nikoense, Glycyrrhiza glabra, Lagerstroemia speciosa, Psidium guajava and Thea sinensis, showed high activity. Of these, the extracts from A. nikoense, G. glabra and T. sinensis were fractionated by extraction with CHCl3, and the CHCl3-soluble fractions from G. glabra showed antifungal activity with minimum inhibitory concentrations (MICs) between 62.5 and 125 microg/ml against the above-mentioned two fungi. When the EtOAc-soluble fraction of A. nikoense was used, the MIC against A. sacchari M001 was 62.5 microg/ml. However, none of the fractions from A. nikoense or T. sinensis showed high activity against C. funicola M002 and their MICs were greater than 500 microg/ml. A licorice preparation made from the commercially available oil-based extract of G. glabra showed a low MIC of 25 microg/ml against five tested strains of filamentous fungi, but not against Aspergillus fumigatus M008, in a blended tea. Consequently, the possibility of adding a licorice preparation made from the oil-based extract of G. glabra to tea beverages (aseptically filled into PET bottles) was suggested.

PMID: 16232887 [PubMed]

60. Determination of glabridin in human plasma by solid-phase extraction and LC-MS/MS.

Aoki F, Nakagawa K, Tanaka A, Matsuzaki K, Arai N, Mae T.

Research and Development Group, Functional Food Ingredients Division, Kaneka Corporation, 1-8 Miyamae-machi, Takasago-cho, Takasago, Hyogo 676-8688, Japan. Fumiki.Aoki@kn.kaneka.co.jp

Glabridin is a major flavonoid included specifically in licorice (Glycyrrhiza glabra L.), and has various physiological activities including antioxidant and anti-inflammatory effects. We have developed and validated an analytical method for determination of glabridin in human plasma by solid-phase extraction (SPE) and LC-MS/MS. Glabridin was extracted from plasma by SPE using a C8 cartridge and analyzed by LC-MS/MS using mefenamic acid as an internal standard (IS). The analyte were separated by a C18 column on LC, and monitored with a fragment ion of m/z 201 formed from a molecular ion of m/z 323 for glabridin and that of m/z 196 from m/z 240 for IS during negative ion mode with tandem MS detection. The lower limit of quantitation (LLOQ) of glabridin was 0.1 ng/mL in plasma, corresponding to 1.25 pg injected on-column. The calibration curves exhibited excellent linearity (r>0.997) between 0.1 and 50 ng/mL. Precision and accuracy were <17 and <+/-7% at LLOQ, and <11 and <+/-5% at other concentrations. Glabridin was recovered >90%, and was stable when kept at 10 degrees C for 72 h, at -20 degrees C until 12 weeks, and after three freeze-thaw cycles. This is the first report on determination of glabridin in body fluids by the selective, sensitive, and reproducible method.

PMID: 16183339 [PubMed - indexed for MEDLINE]

62. Binding of phytoestrogens to rat uterine estrogen receptors and human sex hormone-binding globulins.

Hillerns PI, Zu Y, Fu YJ, Wink M.

Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.

The interaction of phytoestrogens with the most important binding sites of steroid hormones, i.e. sex hormone-binding globulin and estrogen receptors, was investigated. Relative binding affinities and association constants for 21 compounds among them isoflavones, flavones, flavonols, flavanones, chalcones and lignans were determined. The lignan nordihydroguaiaretic acid weakly displaced 17beta-[3H]-estradiol from estrogen receptor and Scatchard analysis suggests non-conformational changes. Compounds from Glycyrrhiza glabra, liquiritigenin and isoliquiritigenin, showed estrogenic affinities to both receptors. 18beta-Glycyrrhetinic acid displaced 17beta-[3H]-estradiol from sex hormone-binding globulin but not from the estrogen receptor. Phytoestrogens compete with 17beta-estradiol much stronger than with 5alpha-dihydrotestosterone for binding to sex hormone-binding globulin.

Publication Types: PMID: 16163844 [PubMed - indexed for MEDLINE]

63. Allelopathic effects of weeds extracts against seed germination of some plants.

Kadioglu I, Yanar Y, Asav U.

Gaziosmanpasa University, Agricultural Faculty, 60250 Tokat, Turkey. izzetk@gop.edu.tr

This study investigated the allelopathic effects of various weeds extracts on seed germination of 11 crop species. Most of the weed extracts tested had inhibitory effects on seed germination of common bean, tomato, pepper, squash, onion, barley, wheat, and corn at different application rates as compared with the 10% acetone control. Chickpea seed germination was inhibited by extracts of Solanum nigrum L., Chenopodium album L., and Matricaria chamomilla L. (10%, 20% and 22.5%, respectively) at the end of 21 day incubation period. However, Glycyrrhiza glabra L., Sorghum halepense (L.) Pers., and Reseda lutea L. extracts stimulated chickpea seed germination at the rates of 95%, 94%, and 93%, respectively, compared to control. It was concluded that some of the weed extracts tested in this study could be used as inhibitor while others could be used as stimulator for the crops.

PMID: 16161968 [PubMed - indexed for MEDLINE]

64. Two new compounds from Glycyrrhiza glabra.

Li JR, Wang YQ, Deng ZZ.

Pharmaceutical Department, Medical College of the Chinese People Armed Police Force, Tianjin 300162, China. jirenli@sina.com.cn

Two new flavonosides have been isolated from the roots of Glychirriza glabra and identified as 5,8-dihydroxy-flavone-7-O-beta-D-glucuronide, glychionide A, and 5-hydroxy-8-methoxyl-flavone-7-O-beta-D-glucuronide, glychionide B.

PMID: 16087644 [PubMed - indexed for MEDLINE]

65. Dihydrostilbene derivatives from Glycyrrhiza glabra leaves.

Biondi DM, Rocco C, Ruberto G.

Istituto del C.N.R. di Chimica Biomolecolare, Sezione di Catania, Via del Santuario 110, I-95028 Valverde CT, Italy.

Four new dihydrostilbenes, alpha,alpha'-dihydro-3,5-dihydroxy-4'-acetoxy-5'-isopentenylstilbene (1), alpha,alpha'-dihydro-3,3',4'-trihydroxy-5-O-isopentenyl-6-isopentenylstilbene (2), alpha,alpha'-dihydro-3,5,3'-trihydroxy-4'-methoxystilbene (3), and alpha,alpha'-dihydro-3,3'-dihydroxy-5beta-d-O-glucopyranosyloxy-4'-methoxystilbene (4), together with seven known flavonoids, glabranin isomer, naringenin, lupiwighteone, pinocembrin 7-O-glucoside, astragalin, isoquercitrin, vicenin II, and the inositol, pinitol, were isolated from the leaves of Glycyrrhiza glabra grown in Sicily. The structures of 1-4 were elucidated by spectroscopic methods.

Publication Types: PMID: 16038558 [PubMed - indexed for MEDLINE]

66. Separation and analysis of glycyrrhizin, 18beta-glycyrrhetic acid and 18alpha-glycyrrhetic acid in liquorice roots by means of capillary zone electrophoresis.

Sabbioni C, Mandrioli R, Ferranti A, Bugamelli F, Saracino MA, Forti GC, Fanali S, Raggi MA.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Glycyrrhizin is the main active compound of Glycyrrhiza glabra root extracts; according to recent studies, glycyrrhizin and its aglycon, glycyrrhetic acid, have interesting therapeutic properties. A new capillary electrophoretic method has been developed for the separation and quantification of glycyrrhizin, beta-glycyrrhetic acid and its isomer a-glycyrrhetic acid. Separation of the analytes was achieved in less than 3 min on a fused silica capillary, by injecting the samples at the short end of the capillary (effective length: 8.5 cm). The background electrolyte was composed of pH 10.0 carbonate buffer, methanol and ethylene glycol (80/10/10) and contained 0.4% beta-cyclodextrin; indomethacin was used as the internal standard. Diode array detection was used, with quantitative assays carried out at 254 nm. Linearity was found over the 5-200 and 2.5-100 microg mL(-1) concentration ranges for glycyrrhizin and glycyrrhetic acid, respectively. This method has been applied to the determination of the analytes in different matrices (liquorice roots and commercial confectionery products), and to the purity control of beta-glycyrrhetic acid obtained from the hydrolysis of glycyrrhizin. When analysing beta-glycyrrhetic acid and its epimer in roots, the samples were purified by means of a suitable solid-phase extraction (SPE) procedure with Oasis HLB cartridges, which granted good selectivity, eliminating matrix interference.

Publication Types: PMID: 16013600 [PubMed - indexed for MEDLINE]

67. Antioxidant properties of some hydroalcoholic plant extracts with antiinflammatory activity.

Herold A, Cremer L, Calugăru A, Tamaş V, Ionescu F, Manea S, Szegli G.

NIRDMI "Cantacuzino", Bucharest, Romania.

The hydroalcoholic extracts of Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra which exhibited different anti-inflammatory activities were evaluated for the possible mode of action by studying their antioxidant potential. In the present study we investigated if standardized hydroalcoholic extracts of plants such as Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra produced by Hofigal Stock Company could modulate the respiratory burst of human activated neutrophils, as a consequence of their antioxidant capacity. Their antioxidant properties were measured using a colorimetric assay (Total Antioxidant Status kit). We demonstrated that Hypericum perforatum and Calendula officinalis hydroalcoholic extracts possessed a significant antioxidant activity while Plantago lanceolata and Glycyrrhiza glabra hydroalcoholic extracts had a minor antioxidant status. Using reactive oxygen species-generating systems (OZ-activated human PMN neutrophils), Calendula officinalis and Hypericum perforatum extracts showed strong reactive oxygen species scavenging property, Hypericum perforatum extract exhibing the highest scavenging activity. These results confirm the potential of Calendula officinalis and Hypericum perforatum investigated hydroalcoholic extracts as medicinal remedies to be used in different inflammatory/allergic diseases. These extracts could be a useful tool for obtaining new antioxidant/anti-inflammatory agents.

Publication Types: PMID: 16008145 [PubMed - indexed for MEDLINE]

68. The isolation and structure elucidation of minor isoflavonoids from licorice of Glycyrrhiza glabra origin.

Kinoshita T, Tamura Y, Mizutani K.

Faculty of Pharmaceutical Sciences, Teikyo University, Tsukui-gun, Kanagawa, Japan. tk-1948@pharm.teikyo-u.ac.jp

Two new isoflavanone and one new 3-arylcoumarin derivatives, along with a known compound 3,4-didehydroglabridin, were isolated from commercially available licorice of Glycyrrhiza glabra origin, and their structures were elucidated on the basis of both the chemical and spectroscopic evidence.

Publication Types: PMID: 15997151 [PubMed - indexed for MEDLINE]

69. Analysis and comparison of Radix Glycyrrhizae (licorice) from Europe and China by capillary-zone electrophoresis (CZE).

Rauchensteiner F, Matsumura Y, Yamamoto Y, Yamaji S, Tani T.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan. florian_rauchensteiner@yahoo.de

A simple capillary-zone electrophoresis (CZE) method for the analysis of plant specimens, Glycyrrhiza glabra L., G. uralensisFisch. and G. inflata Bat. (Leguminosae) as well as commercial licorices from Europe and China was developed. Contents of glycyrrhizin (GL), glycyrrhetic acid (GA), glabridin (GLAB), liquiritin (LQ) and licochalcone A (LC(A)) in ethanolic extracts were investigated. Optimum separation was achieved with sodium tetraborate buffer (pH 9.22; 70 mM); voltage, 25 kV. Recovery rate for GL was found to be 101.90+/-2.54%. Adequate correlation was observed between GL contents measured by CZE and HPLC (r=0.977). Advantages over conventional HPLC analysis of Glycyrrhiza species are short analysis time (<15 min), simple running buffer preparation and the none-use of organic solvents. Using the present CZE method, it was demonstrated that (1) G. glabra was distinguished from G. uralensis especially by phenolic compounds GLAB (G. glabra: 0.19+/-0.11%; n=53) and LQ (G. uralensis, 1.34+/-0.34%, n=10); (2) on average, GL contents were higher in Chinese commercial licorices; (3) relatively high LC(A) contents were especially detected in a Chinese commercial licorice (origin estimated as G. inflata); (4) Glycyrrhiza species were also distinguished by applying PCA on the basis of CZE peak area data of GL, GLAB, GA, LQ and LC(A); and (5) liquiritin apioside was found in all samples.

Publication Types: PMID: 15967286 [PubMed - indexed for MEDLINE]

70. Antioxidant activity of DHC-1, an herbal formulation, in experimentally-induced cardiac and renal damage.

Bafna PA, Balaraman R.

Pharmacy Department, Faculty of Technology and Engineering, The M.S. University of Baroda, Baroda -390 001, Gujarat, India.

DHC-1, an herbal formulation derived from the popular plants Bacopa monniera, Emblica officinalis, Glycyrrhiza glabra, Mangifera indica and Syzygium aromaticum was studied for its antioxidant activity. The protective effect of DHC-1 in isoproterenol-induced myocardial infarction and cisplatin-induced renal damage were studied. A significant reduction in the serum markers of heart and kidney damage and the extent of lipid peroxidation with a concomitant increase in the enzymatic (SOD and CAT) and non-enzymatic antioxidants (reduced glutathione) were observed in DHC-1 pretreated animals compared with the isoproterenol or cisplatin alone treated animals. Thus it can be concluded that DHC-1 possesses a protective effect against both damaged heart and kidneys in rats. This beneficial effect may be attributed, at least in part, to its antioxidant activity. Copyright 2005 John Wiley & Sons, Ltd.

Publication Types: PMID: 15934019 [PubMed - indexed for MEDLINE]

71. Anti-ulcer and anti-oxidant activity of pepticare, a herbomineral formulation.

Bafna PA, Balaraman R.

Department of Pharmacy, Faculty of Technology and Engineering, M.S. University of Baroda, Kalabhavan, Baroda 390 001, Gujarat, India.

Pepticare, a herbomineral formulation of the Ayurveda medicine consisting of the herbal drugs: Glycyrrhiza glabra, Emblica officinalis and Tinospora cordifolia, was tested for its anti-ulcer and anti-oxidant activity in rats. Effects of various doses (125, 250, 500 and 1000mg/kg, p.o.) of Pepticare were studied on gastric secretion and gastric ulcers in pylorus-ligation and on ethanol-induced gastric mucosal injury in rats. The reduction in ulcer index in both the models along with the reduction in volume and total acidity, and an increase in the pH of gastric fluid in pylorus-ligated rats proved the anti-ulcer activity of Pepticare. It was also found that Pepticare was more potent than G. glabra alone in protecting against pylorus-ligation and ethanol-induced ulcers. The increase in the levels of superoxide dismutase, catalase, reduced glutathione and membrane bound enzymes like Ca2+ ATPase, Mg2+ ATPase and Na+ K+ ATPase and decrease in lipid peroxidation in both the models proved the anti-oxidant activity of the formulation. Thus it can be concluded that Pepticare possesses anti-ulcer activity, which can be attributed to its anti-oxidant mechanism of action.

Publication Types: PMID: 15898703 [PubMed - indexed for MEDLINE]

72. Plant medicines of Indian origin for wound healing activity: a review.

Biswas TK, Mukherjee B.

Department of Sharira Kriya, J. B. Roy State Ayurvedic Medical College and Hospital.

Research on wound healing drugs is a developing area in modern biomedical sciences. Scientists who are trying to develop newer drugs from natural resources are looking toward the Ayurveda, the Indian traditional system of medicine. Several drugs of plant, mineral, and animal origin are described in the Ayurveda for their wound healing properties under the term Vranaropaka. Most of these drugs are derived from plant origin. Some of these plants have been screened scientifically for the evaluation of their wound healing activity in different pharmacological models and patients, but the potential of most remains unexplored. In a few cases, active chemical constituents were identified. Some Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon, Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa, Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica, Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental models. This paper presents a limited review of plants used in Ayurvedic medicine.

PMID: 15866825 [PubMed]

73. Microbiological quality of sous and tamarind, traditional drinks consumed in Jordan.

Nassereddin RA, Yamani MI.

Department of Nutrition and Food Technology, Faculty of Agriculture, University of Jordan, Amman, Jordan.

This study was conducted to evaluate the microbiological quality of sous (a drink prepared by extracting dried roots of Glycyrrhiza glabra) and tamarind (a drink prepared by infusing Tamarindus indica dried pulp), traditional drinks consumed in Jordan. Twenty-one samples of sous and 44 samples of tamarind were collected from the local market in Amman, Jordan. Water is the major component of the drinks. Sous drink is characterized by having an alkaline pH (range, 6.6 to 9.9; mean, 8.6), whereas tamarind drink has an acidic pH (range, 1.8 to 3.7; mean, 2.8). The drinks are not processed for safety before serving, and at some vendors drinks are not properly refrigerated. The mean counts for aerobic bacteria, lactic acid bacteria, and yeasts in sous drink samples were 5.9, 5.0, and 3.8 log CFU/ml, respectively; those in tamarind drink samples were 4.0, <1, and 5.8 log CFU/ml, respectively. The lactic acid bacteria isolated were Enterococcus raffinosus, Enterococcus hirae, Enterococcus durans, Lactobacillus acidophilus, and Lactobacillus buchneri. The yeast isolates in sous drink were from the genera Candida, Filobasidium, Hanseniaspora, Lodderomyces, Pichia, and Williopsis, and those in tamarind drink were from Arthroascus, Brettanomyces, Candida, Debaromyces, Filobasidiella, Hanseniaspora, Klavispora, Lodderomyces, Pichia, Saccharomycodes, Trichosporon, and Zygosaccharomyces. Enterobacteriaceae were detected in two sous samples and were identified as Enterobacter sakazakii and Erwinia sp., and in two tamarind samples and were identified as Citrobacter freundii and Klebsiella pneumoniae. Salmonella was detected in one sous and one tamarind sample. Pseudomonas aeruginosa was detected in only one sous sample. These findings highlight the importance of application of hygienic practices throughout preparation and vending of drinks, starting with raw ingredients and continuing through preparation, storage, display, and serving.

PMID: 15830669 [PubMed - indexed for MEDLINE]

74. Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts.

Di Mambro VM, Fonseca MJ.

Department of Pharmaceutical Science, Faculty of Pharmaceutical Sciences of Ribeirăo Preto, USP, Av. do Café s/n, 14040-903 Ribeirăo Preto, SP, Brazil. valeriadimambro@yahoo.com.br

In the present investigation the changes on physical stability (pH, viscosity, flow index and tixotropy) of topical formulations were evaluated following inclusion of different plant extracts containing flavonoids. Also, the antioxidant effect of these plant extracts alone and after addition in the formulation was evaluated using chemiluminescence and the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH(.-)) assays, as well as the inhibition of lipid peroxidation. Formulation added with dl-alpha-tocopherol was used to compare the physical stability and antioxidant activity. Formulations with plant extracts showed pseudoplastic behavior with decreasing on viscosity and tixotropy. The Glycyrrhiza glabra (GG) and Ginkgo biloba (GB) extracts alone and the formulations containing these extracts showed great antioxidant and free radical scavenging activities while the other extracts studied (mixture of Glycyrrhiza glabra, Symphytum officinale L and Arctium majus root, Nelumbium speciosum and soybean) showed lower activity. The results suggest that GG and GB extracts may be used in topical formulations in order to protect skin against damage caused by free radical and reactive oxygen species.

Publication Types: PMID: 15708669 [PubMed - indexed for MEDLINE]

75. Memory-strengthening activity of Glycyrrhiza glabra in exteroceptive and interoceptive behavioral models.

Parle M, Dhingra D, Kulkarni SK.

Pharmacology Division, Department of Pharmaceutical Sciences, Guru Jambheshwar University, Hisar, Haryana, India. mparle@rediffmail.com

In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza glabra have been employed clinically for centuries for their anti-inflammatory, anti-ulcer, expectorant, antimicrobial, and anxiolytic activities. The present study was undertaken to investigate the effects of G. glabra, popularly known as liquorice (Mulathi), on learning and memory. The elevated plus-maze and passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (75, 150, and 300 mg/kg p.o.) of aqueous extract of G. glabra were administered for 7 successive days in separate groups of mice. The dose of 150 mg/kg of the aqueous extract of liquorice significantly improved learning and memory of mice. Furthermore, this dose reversed the amnesia induced by diazepam (1 mg/kg i.p.), scopolamine (0.4 mg/kg i.p.), and ethanol (1 g/kg i.p.). Anti-inflammatory and antioxidant properties of liquorice may be contributing favorably to the memory enhancement effect. Since scopolamine-induced amnesia was reversed by liquorice, it is possible that the beneficial effect on learning and memory may be because of facilitation of cholinergic transmission in brain. However, further studies are necessitated to identify the exact mechanism of action. In the present investigation, G. glabra has shown promise as a memory enhancer in both exteroceptive and interoceptive behavioral models of memory.

Publication Types: PMID: 15671690 [PubMed - indexed for MEDLINE]

76. Phylogenetic relationship of Glycyrrhiza lepidota, American licorice, in genus Glycyrrhiza based on rbcL sequences and chemical constituents.

Hayashi H, Miwa E, Inoue K.

Gifu Pharmaceutical University, Gifu, Japan. hayashih@gifu-pu.ac.jp

Two known saponins, licorice-saponin H2 and macedonoside A, were isolated from the stolons of Glycyrrhiza lepidota (American licorice) as major saponins. Since licorice-saponin H2 and macedonoside A are minor saponins isolated from the three glycyrrhizin-producing species (i.e. G. glabra, G. uralensis, G. inflata) and the three macedonoside C-producing species (i.e. G. macedonica, G. echinata, G. pallidiflora), respectively, the present study suggests that G. lepidota is an intermediate of both glycyrrhizin-producing and macedonoside C-producing species. The phylogenetic tree constructed from the nucleotide sequences of ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) of these seven Glycyrrhiza plants indicated that G. lepidota was separated from the other six Glycyrrhiza species, and this phylogenetic relationship was in accordance with their saponin compositions.

PMID: 15635184 [PubMed - indexed for MEDLINE]

77. Licorice flavonoids suppress abdominal fat accumulation and increase in blood glucose level in obese diabetic KK-A(y) mice.

Nakagawa K, Kishida H, Arai N, Nishiyama T, Mae T.

Functional Foods Development Division, Kaneka Corporation, Osaka, Japan.

Licorice, the root of the Glycyrrhiza species, is one of the most frequently employed botanicals in traditional medicines. In this study, we investigated the effects of hydrophobic flavonoids from Glycyrrhiza glabra LINNE on abdominal fat accumulation and blood glucose level in obese diabetic KK-A(y) mice. In order to enrich a fraction of hydrophobic flavonoids, licorice flavonoid oil (LFO) was prepared by further extracting licorice ethanolic extract with medium-chain triglycerides (MCT), and adjusting the concentration of glabridin, the major flavonoid of licorice, to 1.2% in oil. KK-A(y) mice aged 6 weeks were assigned to 5 groups (n=6 each), and fed a high-fat diet containing 0 (control), 0.5%, 1%, or 2% LFO, or 0.5% conjugated linoleic acid (CLA) for 4 weeks. Compared with the control, body weight gain and weights of abdominal adipose tissues were suppressed (p<0.05) by feeding the diet containing 2% LFO, and blood glucose levels after 2 and 4 weeks were suppressed by all of the diets containing LFO. Although CLA feeding suppressed (p<0.05) body weight gain, it increased (p<0.05) blood glucose level after 2 weeks compared with the control level. Furthermore, LFO and licorice ethanolic extract stimulated human adipocyte differentiation in vitro. These results indicate that licorice hydrophobic flavonoids have abdominal fat-lowering and hypoglycemic effects, possibly mediated via activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma).

PMID: 15516721 [PubMed - indexed for MEDLINE]

78. Hydroalcoholic plant extracts with anti-inflammatory activity.

Herold A, Cremer L, Călugaru A, Tamaş V, Ionescu F, Manea S, Szegli G.

National Institute of Research-Developmentfor Microbiology and Immunology Cantacuzino, Bucharest, Romania.

The aim of the present study was to investigate if standardized hydroalcoholic plant extracts such as Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra can suppress in cell-free systems the activities of 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2), key enzymes in the formation of proinflammatory eicosanoids from arachidonic acid (AA). Studies were undertaken to compare the above mentioned plant extracts to a known NSAID (nimesulide) in their ability to inhibit both cyclooxygenase (COX-2) and lipoxygenase (5-LO) activities in cell-free systems. We report on 2 vegetal extracts (Hypericum perforatum and Glycyrrhiza glabra) that inhibit 5-LO activity and 2 vegetal extracts (Plantago lanceolata and Glycyrrhiza glabra) that inhibit COX-2 activity. In this study, we demonstrate for the first time that Glycyrrhiza glabra extract efficiently suppresses both eicosanoids and leukotrienes formation in cell-free systems, implying that this extract directly acts as a dual inhibitor of 5-LO and COX-2 activities. With regard to the properties of dual COX-2/5-LO inhibitors, Glycyrrhiza glabra extract might be a potential drug possessing anti-inflammatory activity devoid of the most troublesome (gastric) side effects seen for drugs used as COX-2 and 5-LO inhibitors. Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra extracts can be added to an already impressive list of these species that have anti-inflammatory activity.

Publication Types: PMID: 15493372 [PubMed - indexed for MEDLINE]

79. [Effects of nutrient solution concentration on inorganic and glycyrrhizin contents of Glycyrrhiza glabra Linn]

[Article in Japanese]

Sato S, Ikeda H, Furukawa H, Murata Y, Tomoda M.

Faculty of Horticulture, Chiba University, Matsudo City 271-8510, Japan. s.sato@faculty.chiba-u.jp

Licorice, Glycyrrhiza glabra Linn., is one of herbal medicines widely used for various purposes, including as a sweetener and for gastric ulcer treatment. However, environmental destruction due to the harvesting of wild licorice is becoming a serious problem. We cultured licorice in a hydroponic system to examine the relation between the concentration of nutritional solution applied and glycyrrhizin content to determine the optimal nutrient solution concentration for commercial licorice production. Licorice growth and glycyrrhizin content in the root reached the highest values when the plants received nutrient solution approximately equivalent to a quarter unit of Hoagland solution. The results also indicated that the glycyrrhizin content does not correlate with the concentration of nutrient solution applied and/or inorganic contents absorbed, i.e., licorice may absorb large amounts of nutrient solution but the glycyrrhizin content may not increase.

Publication Types: PMID: 15467279 [PubMed - indexed for MEDLINE]

80. Oriental medicinal herb, Periploca sepium, extract inhibits growth and IL-6 production of human synovial fibroblast-like cells.

Tokiwa T, Harada K, Matsumura T, Tukiyama T.

Kohno Clinical Medicine Research Institute, Shinagawa-ku, Tokyo, Japan. t.tokiwa@kcmi.or.jp

Periploca sepium (PS) has traditionally been used in oriental medicine for treatment of rheumatoid arthritis (RA). We investigated the aqueous extract of PS (PSE) in its effects on human rheumatoid arthritis-derived fibroblast-like cells. In cell culture studies, PSE inhibited the growth and IL-6 production of the cells in dose dependent manners. The extract of Glycyrrhiza glabra (GG), which has also been used to treat RA and chosen as a reference here, slightly inhibited the growth of RA cells. A study of PSE fractionation indicated that the active material inhibiting IL-6 production is filterable by ultrafiltration, suggesting that substances with low molecular weight might be involved in an inhibition of IL-6 production. These results support the view that PSE represents a rich source of growth inhibition and anti-IL 6 production.

Publication Types: PMID: 15467222 [PubMed - indexed for MEDLINE]

81. Anticariogenic activity of some tropical medicinal plants against Streptococcus mutans.

Hwang JK, Shim JS, Chung JY.

Department of Biotechnology and Bioproducts Research Center, Yonsei University, Seoul 120-749, South Korea. jkhwang@yonsei.ac.kr

The methanol extracts of five tropical plants, Baeckea frutescens, Glycyrrhiza glabra, Kaempferia pandurata, Physalis angulata and Quercus infectoria, exhibited potent antibacterial activity against the cariogenic bacterium Streptococcus mutans. In particular, G. glabra, K. pandurata and P. angulata conferred fast killing bactericidal effect against S. mutans in 2 min at 50 microg/ml of extract concentration.

Publication Types: PMID: 15351117 [PubMed - indexed for MEDLINE]

82. Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells.

Fu Y, Hsieh TC, Guo J, Kunicki J, Lee MY, Darzynkiewicz Z, Wu JM.

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.

Licochalcone (LA) is a novel estrogenic flavonoid isolated from PC-SPES composition herb licorice root that was reported to show significant antitumor activity in various malignant human cell lines. To better understand its anti-CaP activities, we have investigated LA-elicited growth control and induction of apoptosis using androgen-independent p53-null PC-3 prostate cancer cells. LA induced modest level of apoptosis but had more pronounced effect on cell cycle progression arresting cells in G2/M, accompanied by suppression of cyclin B1 and cdc2. It also inhibited phosphorylation of Rb, specifically phosphorylation of S780 with no change of phosphorylation status of T821, decreased expression of transcription factor E2F concurrent with reduction of cyclin D1, down-regulation of CDKs 4 and 6, but increased cyclin E expression. These findings provide mechanistic explanation for LA activity and suggest that it may be considered as a chemopreventive agent and its anticancer properties should be further explored.

Publication Types: PMID: 15313200 [PubMed - indexed for MEDLINE]

83. Differential expression of three oxidosqualene cyclase mRNAs in Glycyrrhiza glabra.

Hayashi H, Huang P, Takada S, Obinata M, Inoue K, Shibuya M, Ebizuka Y.

Gifu Pharmaceutical University, Japan. hayashih@gifu-pu.ac.jp

The cultured cells and intact plants of Glycyrrhiza glabra (Fabaceae) produce betulinic acid and oleanane-type triterpene saponins (soyasaponins and glycyrrhizin). To elucidate the regulation of triterpenoid biosynthesis in G. glabra, the cDNA of lupeol synthase, an oxidosqualene cyclase (OSC) responsible for betulinic acid biosynthesis, was cloned, and expression patterns of lupeol synthase and two additional OSCs, beta-amyrin synthase and cycloartenol synthase, were compared. The mRNA expression levels of lupeol synthase and beta-amyrin synthase were consistent with the accumulation of betulinic acid and oleanane-type triterpene saponins, respectively. The transcript of lupeol synthase was highly expressed in the cultured cells and root nodules. The transcript of beta-amyrin synthase, an OSC responsible for oleanane-type triterpene biosynthesis, was highly expressed in the cultured cells, root nodules and germinating seeds, where soyasaponin accumulates, and in the thickened roots where glycyrrhizin accumulates. In the cultured cells, the addition of methyl jasmonate up-regulated beta-amyrin synthase mRNA and soyasaponin biosynthesis, but down-regulated lupeol synthase mRNA. Furthermore, the addition of gibberellin A(3) down-regulated beta-amyrin synthase mRNA but not lupeol synthase mRNA in the cultured cells. The mRNA levels of cycloartenol synthase, an additional OSC responsible for sterol biosynthesis, in the intact plant and cultured cells were relatively constant in these experiments.

Publication Types: PMID: 15256745 [PubMed - indexed for MEDLINE]

84. Neuropharmacological actions of panchagavya formulation containing Emblica officinalis Gaerth and Glycyrrhiza glabra Linn in mice.

Achliya GS, Wadodkar SG, Avinash KD.

Department of Pharmaceutical Sciences, Nagpur University, Amravati Road, Nagpur 440 033, India. achliya@yahoo.com

A panchagavya Ayurvedic formulation containing E. officinalis, G. glabra, and cow's ghee was evaluated for its effect on pentobarbital-induced sleeping time, pentylenetetrazol-induced seizures, maximal electroshock-induced seizures, spontaneous motor activity, rota-rod performance (motor coordination) and antagonism to amphetamine in mice. The formulation (300, 500 mg/kg, po) produced a significant prolongation of pentobarbital-induced sleeping time and reduced spontaneous locomotor activity. The formulation also significantly antagonised the amphetamine induced hyper-locomotor activity (500, 750 mg/kg, po) and protected mice against tonic convulsions induced by maximal electroshock (500, 750 mg/kg, po). The formulation slightly prolonged the phases of seizure activity but did not protect mice against lethality induced by pentylenetetrazole. The formulation did not show neurotoxicity. The results suggest that the panchagavya formulation is sedative in nature.

PMID: 15233476 [PubMed - indexed for MEDLINE]

85. Variability in the content of active constituents and biological activity of Glycyrrhiza glabra.

Statti GA, Tundis R, Sacchetti G, Muzzoli M, Bianchi A, Menichini F.

Dipartimento di Scienze Farmaceutiche, Universitŕ degli Studi della Calabria, via Pietro Bucci, I-87036 Arcavacata di Rende (CS), Italy.

Nine samples of Glycyrrhiza glabra were collected in various sites of Calabria, Italy, with the aim to determine the variability in the confront of active constituents and in antibacterial and antifungal activities of the extracts. The samples showed remarkable differences in chemical composition and biological activity. Copyright 2004 Elsevier B.V.

PMID: 15158998 [PubMed - indexed for MEDLINE]

86. Complementary and alternative therapies in the treatment of chronic hepatitis C: a systematic review.

Coon JT, Ernst E.

Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, UK. jo.thompson-coon@pms.ac.uk

BACKGROUND/AIMS: Hepatitis C is an escalating global health problem. The recommended treatment regimen is associated with considerable expense, adverse effects and poor efficacy in some patients. Complementary therapies are widely promoted for and used by patients with hepatitis C. The aim is to systematically assess the efficacy of complementary therapies in treating chronic hepatitis C. METHODS: Systematic searches were conducted in six databases, reference lists of all papers were checked for further relevant publications and information was requested from experts. No language restrictions were imposed. RESULTS: Twenty-seven eligible randomised clinical trials were located involving herbal products and supplements. No randomised clinical trials were identified for any other complementary therapy. In 14 of the trials, patients received interferon-alpha in combination with the complementary therapy. Less than half the trials (11/27) were of good methodological quality. Compared with the control group, significant improvements in virological and/or biochemical response were seen in trials of vitamin E, thymic extract, zinc, traditional Chinese medicine, Glycyrrhiza glabra and oxymatrine. CONCLUSIONS: We identified several promising complementary therapies, although extrapolation of the results is difficult due to methodological limitations. More research is warranted to establish the role of these and other therapies in the treatment of hepatitis C.

Publication Types: PMID: 15123365 [PubMed - indexed for MEDLINE]

87. Memory enhancing activity of Glycyrrhiza glabra in mice.

Dhingra D, Parle M, Kulkarni SK.

Pharmacology Division, Department of Pharmaceutical Sciences, P.O. Box 38, Guru Jambheshwar University, Hisar 125001, Haryana, India. din_dhingra@yahoo.com

In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza glabra (family: Leguminosae) have been employed clinically for centuries for their anti-inflammatory, antiulcer, expectorant, antimicrobial and anxiolytic activities. The present study was undertaken to investigate the effects of Glycyrrhiza glabra (popularly known as liquorice) on learning and memory in mice. Elevated plus-maze and passive avoidance paradigm were employed to test learning and memory. Three doses (75, 150 and 300 mg/kg p.o.) of aqueous extract of Glycyrrhiza glabra were administered for 7 successive days in separate groups of animals. The dose of 150 mg/kg of the aqueous extract of liquorice significantly improved learning and memory of mice. Furthermore, this dose significantly reversed the amnesia induced by diazepam (1 mg/kg i.p.) and scopolamine (0.4 mg/kg i.p.). Anti-inflammatory and antioxidant properties of liquorice may be contributing favorably to the memory enhancement effect. Since scopolamine-induced amnesia was reversed by liquorice, it is possible that the beneficial effect on learning and memory was due to facilitation of cholinergic-transmission in mouse brain. However, further studies are necessitated to identify the exact mechanism of action. In the present investigation, Glycyrrhiza glabra has shown promise as a memory enhancing agent in all the laboratory models employed.

Publication Types: PMID: 15120462 [PubMed - indexed for MEDLINE]

88. Phytoestrogens in botanical dietary supplements: implications for cancer.

Piersen CE.

UIC/NIH Center for Botanical Dietary Supplements Research in the Program for Collaborative Research in the Pharmaceutical Sciences, University of Illinois at Chicago, College of Pharmacy, 60612, USA. cpiersen@uic.edu

Phytoestrogens are plant constituents that possess either estrogenic or antiestrogenic activity. Although their activities are weak as compared with human endogenous estrogens, the consumption of phytoestrogens may have clinically significant consequences. A number of botanicals, or the compounds contained therein, have been identified as putative estrogenic agents, but consensus in the biomedical community has been hampered by conflicting data from various in vitro and in vivo models of estrogenic activity. Phytoestrogens may serve as chemopreventive agents while at the same time being capable of promoting growth in estrogen receptor positive cancer cell lines. Furthermore, they may exert their estrogenic influence through receptor-dependent and/or receptor-independent mechanisms. These findings have led to speculation that phytoestrogen intake might be ill advised for patients at an increased risk for hormone-dependent cancers, cancer patients, or cancer survivors. This article will attempt to sort out discrepancies between various experimental models and establish whether certain herbs possess estrogenic activity. The review will focus on 5 popular botanical dietary supplements: Trifolium pratense (red clover), Cimicifuga racemosa (black cohosh), Humulus lupulus (hops), Angelica sinensis (dong quai), and Glycyrrhiza glabra (licorice). It will address their mechanisms of action, clinical evidence bases, and implications for use in cancer.

Publication Types: PMID: 15035899 [PubMed - indexed for MEDLINE]

89. Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor.

Mendes-Silva W, Assafim M, Ruta B, Monteiro RQ, Guimarăes JA, Zingali RB.

Departamento de Bioquímica Médica, Instituto de Cięncias Biomédicas, Centro de Cięncias da Saúde, Universidade Federal do Rio de Janeiro, 21941-590, Rio de Janeiro, Brazil.

Glycyrrhizin (GL), an anti-inflammatory compound isolated from licorice (Glycyrrhiza glabra), has been previously identified as a thrombin inhibitor (Francischetti et al., Biochem Biophys Res Commun 1997;235:259-63). Here we report the in vivo effects of GL upon two experimental models of induced thrombosis in rats. Intravenous administration of GL caused a dose-dependent reduction in thrombus size on a venous thrombosis model that combines stasis and hypercoagulability. It was observed that GL doses of 180 mg/kg body weight produced 93% decrease on thrombus weight. This effect showed a time-dependent pattern being significantly reduced when the thrombogenic stimulus was applied 60 min after drug administration. GL was also able to prevent thrombosis using an arteriovenous shunt model. GL doses of 180 and 360 mg/kg decreased the thrombus weight by 35 and 90%, respectively. Accordingly, the APTT ex vivo was enhanced by 1.5- and 4.3-fold at GL doses of 180 and 360 mg/kg, respectively. In addition, GL doses above 90 mg/kg caused significant hemorrhagic effect. In contrast with heparin, GL did not potentiate the inhibitory activity of antithrombin III or heparin cofactor II towards thrombin. Altogether, data indicate that GL is an effective thrombin inhibitor in vivo, which may account for its other known pharmacological properties.

Publication Types: PMID: 15013279 [PubMed - indexed for MEDLINE]

90. [Shifts of activity of the succinate dehydrogenase in some brain areas during combined effect of vibration and licorice roots]

[Article in Russian]

Oganisian AO, Oganisian KR, Minasian SM.

Department of Human and Animal Physiology, Yerevan State University, 375025, Yerevan, Manukyan st., 1. Republic of Armenia.

The data obtained demonstrate that, under conditions of 30-day vibrations, feeding of rabbits with Clycyrrhiza glabra L. considerably increases activity of the succinatdehydrogenase enzyme anaerobic respiration in the cortex and decreases it in the subcortex. Under the 30-day combined effect of Clycyrrhiza glabra L. and the vibration, after the preliminary 30-day feeding with Clycyrrhiza glabra L., the high activity of succinatdehydrogenase occurs in all structures under study, energy supply and cytometabolism improve, the vibration effect is abated.

Publication Types: PMID: 14870485 [PubMed - indexed for MEDLINE]

91. Comparison of antioxidant activity of extract from roots of licorice (Glycyrrhiza glabra L.) to commercial antioxidants in 2% hydroquinone cream.

Morteza-Semnani K, Saeedi M, Shahnavaz B.

Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Powdered dry roots of licorice (Glycyrrhiza glabra L.) were extracted with methanol. Licorice extract was tested for antioxidative activity in comparison with antioxidants (sodium metabisulfite and BHT) at 0.1%, 0.5%, 1.0%, and 2.0% w/w in 2% w/w hydroquinone cream. The systems were incubated in a dark room at 25 degrees +/- 0.5 degrees C and 45 degrees +/- 0.5 degrees C for three months. The physical stability and the percentages of hydroquinone remaining after two weeks and one, two, and three months were determined by UV spectrophotometer at 294 nm according to official standard procedures. The experiment revealed that oxidation degradation of hydroquinone was accelerated by heat even with the existence of antioxidants. The higher percentages of remaining hydroquinone were observed for higher antioxidant concentration but showed lower physical stability in the formulation in the presence of commercial antioxidants, especially in the cases of 1.0% and 2.0% BHT. In the third month, at 25 degrees +/- 0.5 degrees C and 45 degrees +/- 0.5 degrees C, the extract demonstrated more antioxidant activity from two other commercial antioxidants at all concentrations, with about 43-53% and 34-46%, respectively, more hydroquinone remaining than in the control system (p<0.001). In the third month, the preparation containing 0.1%, 0.5%, 1.0%, and 2.0% extract gave good physical formulation stability with about 72%, 76%, 78%, and 81 % hydroquinone remaining at 25 degrees +/- 0.5 degrees C and 51%, 55%, 60%, and 63% hydroquinone remaining at 45 degrees +/- 0.5 degrees C, respectively. This suggested the possibility of using a licorice extract at 0.5% and 1.0% as an effective natural antioxidant for substances that are oxidation-susceptible.

Publication Types: PMID: 14730371 [PubMed - indexed for MEDLINE]

92. Preliminary evaluation of antinephritis and radical scavenging activities of glabridin from Glycyrrhiza glabra.

Fukai T, Satoh K, Nomura T, Sakagami H.

Department of Physico-Chemical Analysis, School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. fukai@phar.toho-u.ac.jp

Antinephritis activity of glabridin, a pyranoisoflavan isolated from Glycyrrhiza glabra, was evaluated after its oral administration to mice with glomerular disease (Masugi-nephritis) by measuring the urinary protein excretion, total cholesterol, serum creatinine and blood urea nitrogen levels. Administration of glabridin for 10 days (30 mg kg(-1) day(-1)) reduced the amount of urinary protein excretion from control level (100+/-23 mg/day) to a significantly lower level (47+/-4 mg/day). ESR spectroscopy demonstrated that glabridin neither produced radical, nor affected the radical intensity of sodium ascorbate, suggesting the lack of correlation between the antinephritis activity and radical scavenging activity.

Publication Types: PMID: 14630165 [PubMed - indexed for MEDLINE]

93.Field survey of Glycyrrhiza plants in Central Asia (3). Chemical characterization of G. glabra collected in Uzbekistan.

Hayashi H, Hattori S, Inoue K, Khodzhimatov O, Ashurmetov O, Ito M, Honda G.

Gifu Pharmaceutical University, Mitahora-higashi, Gifu, Japan. hayashih@gifu-pu.ac.jp

The chemical characteristics of Glycyrrhiza glabra L. were investigated at a habitat in Uzbekistan. HPLC analysis of the underground parts indicated that glycyrrhizin contents varied from 3.3 to 6.1% of dry weight, and that glabridin, a species-specific flavonoid for G. glabra, was detected in all underground samples (0.08-0.35% of dry weight). HPLC analysis of the leaves indicated that G. glabra plants collected in the present study could be divided into two types, RT-type and IQ-type, according to their major flavonol glycosides, rutin or isoquercitrin, respectively.

Publication Types: PMID: 14600388 [PubMed - indexed for MEDLINE]

94. The treatment of atopic dermatitis with licorice gel.

Saeedi M, Morteza-Semnani K, Ghoreishi MR.

Department of Pharmaceutics, Mazandaran University of Medical Sciences, Sari, Iran. saeedi_m_2001@yahoo.co.com

Glycyrrhiza glabra L. has been used in herbal medicine for skin eruptions, including dermatitis, eczema, pruritus and cysts. The effect of licorice extract as topical preparation was evaluated on atopic dermatitis. The plant was collected and extracted by percolation with suitable solvent. The extract was standardized, based on Glycyrrhizinic acid by using a titrimetry method. Different topical gels were formulated by using different co-solvents. After standardizing of topical preparations, the best formulations (1% and 2%) were studied in a double-blind clinical trial in comparison with base gel on atopic dermatitis over two weeks (30 patients in each group). Propylene glycol was the best co-solvent for the extract and Carbopol 940 as gelling agent showed the best results in final formulations. The quantity of glycyrrhizinic acid was determined 20.3% in the extract and 19.6% in the topical preparation. Two percent licorice topical gel was more effective than 1% in reducing the scores for erythema, oedema and itching over two weeks (p<0.05). The results showed that licorice extract could be considered as an effective agent for treatment of atopic dermatitis.

Publication Types: PMID: 14522625 [PubMed - indexed for MEDLINE]

95. Field survey of Glycyrrhiza plants in central Asia (2). Characterization of phenolics and their variation in the leaves of Glycyrrhiza plants collected in Kazakhstan.

Hayashi H, Zhang SL, Nakaizumi T, Shimura K, Yamaguchi M, Inoue K, Sarsenbaev K, Ito M, Honda G.

Gifu Pharmaceutical University, Japan. hayashih@gifu-pu.ac.jp

A new prenylated flavanone, licoleafol, and a new prenylated dihydrostilbene, uralstilbene, together with four known compounds, 8-dimethylallyleriodictyol, sophoraflavanone B, gancaonin R, and 6-dimethylallyleriodictyol, were isolated from the leaves of Glycyrrhiza uralensis collected in Kazakhstan. HPLC analysis of the leaves of Glycyrrhiza plants collected in Kazakhstan showed that both G. uralensis-specific and Glycyrrhiza glabra-specific compounds were detected in the leaves of the morphologically intermediate-type plants, suggesting that the intermediate-type plant is a hybrid of G. glabra and G. uralensis. In addition, HPLC profiles of leaf extracts from offspring of intermediate-type plants were divided into the three types: the G. uralensis type, G. glabra type, and the intermediate type. From these results, it appears likely that the intermediate-type plant back-crosses with G. glabra and G. uralensis to generate a G. glabra-type plant and a G. uralensis-type plant, respectively.

Publication Types: PMID: 14519919 [PubMed - indexed for MEDLINE]

96. Small scale rat hepatocyte primary culture with applications for screening hepatoprotective substances.

Nakagiri R, Oda H, Kamiya

Kyowa Hakko Kogyo Co., Ltd., Tsukuba Research Laboratories, 2 Miyukigaoka, Tsukuba-shi, Ibaraki 305-0841, Japan. ryuusuke.nakagiri@kyowa.co.jp

Isolated hepatocytes are known to maintain their physiological functions for over a week when cultured on Matrigel, artificially reconstituted from basement membrane components. Although this culture technique has been frequently used in research on hepatocyte functions, there has been a limitation on its application for small scale experiments due to some technical problems. By using micro-culture plates with 96 round-bottom wells, we succeeded in coating the wells uniformly with Matrigel. When the cultured hepatocytes were treated with either 10 mM, 15 mM, or 20 mM of acetaminophen or 1 mM, 10 mM, or 20 mM of D-galactosamine, the viability of the hepatocytes became 91.1%, 75.3%, 64.7%, and 79.0%, 43.8%, 26.2% of the non-treated control at 48 hours, respectively. Fractionated extracts of Glycyrrhiza glabra L. and Schisandra chinensis Baillon inhibited the action of acetaminophen or D-galactosamine in this model. From these results, we concluded that the microculture system presented here is capable of maintaining the in vivo characteristics of hepatocytes and is suitable for the screening of hepatoprotective substances.

PMID: 12951493 [PubMed - indexed for MEDLINE]

97. Osaka University of Pharmaceutical Sciences, a 4-20-1, Nasahara, Takatsuki 569-1094, Japan.

Some Glycyrrhiza species grown in several domestic research gardens of medicinal plants were collected by the Osaka University of Pharmaceutical Sciences and were cultivated to compare their morphological properties. HPLC profile analysis was performed and index compounds of MeOH extracts of aerial parts and EtOAc extracts of subterranean parts were determined. Glycyrrhizin contents and growth rates of the underground parts of some types of Glycyrrhiza uralensis and Glycyrrhiza glabra were compared and four excellent types were selected as candidates for cultivation. One of them was due to Kanzo-Yashiki (Enzan, Yamanashi prefecture), where G. uralensis was cultivated in the Edo period. Alkaloidal constituents of G. uralensis and G. glabra were also investigated and anabasine (an insecticide) and a new tricyclic alkaloid were obtained.

Publication Types: PMID: 12931658 [PubMed - indexed for MEDLINE]

98. Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

Amaryan G, Astvatsatryan V, Gabrielyan E, Panossian A, Panosyan V, Wikman G.

Republican Children's FMF Center, Yerevan State Medical University, Yerevan, Armenia.

Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special extracts standardized for the content of Andrographolide (4 mg/tablet), Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel groups of patients. The study was conducted in 24 (3-15 years of both genders) patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets of series A (verum) and 10 patients received series B product (placebo). The study medication was taken three times of four tablets daily for 1 month. Daily dose of the andrographolide--48 mg. The primary outcome measures in physician's evaluation were related to duration, frequency and severity of attacks in FMF patients (attacks characteristics score). The patient's self-evaluation was based mainly on symptoms--abdominal, chest pains, temperature, arthritis, myalgia, erysipelas-like erythema. All of 3 features (duration, frequency, severity of attacks) showed significant improvement in the verum group as compared with the placebo. In both clinical and self evaluation the severity of attacks was found to show the most significant improvement in the verum group. Both the clinical and laboratory results of the present phase II (pilot) clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug for the management of patients with FMF.

Publication Types: PMID: 12809357 [PubMed - indexed for MEDLINE]

99. Field survey of Glycyrrhiza plants in Central Asia (1). Characterization of G. uralensis, G. glabra and the putative intermediate collected in Kazakhstan.

Hayashi H, Hattori S, Inoue K, Sarsenbaev K, Ito M, Honda G.

Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan. hayashih@gifu-pu.ac.jp

The characteristics of Glycyrrhiza plants from 12 collection sites in southeastern Kazakhstan were investigated. G. uralensis was observed at 9 of the sites from Almaty to Shu, and G. glabra was observed at 8 sites. At 4 sites near Shu, and 1 site near Almaty, G. glabra and G. uralensis grew together forming a mixed population, and intermediate-type plants between them were also observed at 3 sites. Although two nucleotide substitutions of the chloroplast rbcL gene were observed between G. uralensis and G. glabra, rbcL sequences of the intermediate-types were divided into G. uralensis-type (G-A type) and G. glabra-type (A-T type). HPLC analysis of the roots indicated that species-specific flavonoids, glabridin and glycycoumarin, were detected in the roots of G. glabra and G. uralensis, respectively, but neither flavonoid was detected in underground parts of the intermediate-types. HPLC analysis of their leaves indicated a significant difference among G. uralensis, G. glabra and the intermediate-type plants. Both G. glabra-specific and G. uralensis-specific compounds were detected in the leaves of the intermediate-type, thus suggesting that the intermediate plants are hybrids of G. glabra and G. uralensis.

Publication Types: PMID: 12808302 [PubMed - indexed for MEDLINE]

100. Screening of traditionally used South African plants for antifungal activity against Candida albicans.

Motsei ML, Lindsey KL, van Staden J, Jäger AK.

Research Centre for Plant Growth and Development, School of Botany and Zoology, University of Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa.

Twenty-four South African medicinal plants were screened against Candida albicans standard strain ATCC 10231 and two clinical isolates from a 5-month-old baby and an adult, in an attempt to find a traditional remedy to treat oral candidiasis, which is prevalent in HIV-patients. Allium sativum L. and Tulbaghia violacea L. aqueous bulb extracts had MIC values of 0.56 and 3.25mg/ml respectively, whilst Polygala myrtifolia L. leaves and Glycyrrhiza glabra L. rhizome extracts had MIC values of 1.56 mg/ml when tested against the 5-month-old isolate. Fresh water extracts stored at 4, 23 and 33 degrees C over a period of a week, were used to determine the stability of these extracts. Allium sativum and Tulbaghia violacea maintained activity at 4 degrees C, but not at higher temperatures, whereas Polygala myrtifolia and Glycyrrhiza glabra lost activity within a day even at 4 degrees C. The unpleasant taste of the two species with a garlic smell, could however not be masked, and as the smell following the eating of the two species would lead to HIV-patients being recognised, these two plants where not considered for further investigation. Therefore, Polygala myrtifolia and Glycyrrhiza glabra are being further investigated for use as an oral mouthwash in clinics and homes.

Publication Types: PMID: 12738093 [PubMed - indexed for MEDLINE]

101. Up-regulation of soyasaponin biosynthesis by methyl jasmonate in cultured cells of Glycyrrhiza glabra.

Hayashi H, Huang P, Inoue K.

Department of Pharmacognosy, Gifu Pharmaceutical University, Mitahora-higashi 5-6-1, Gifu, 502-8585 Japan. hayashih@gifu-pu.ac.jp

Exogenously applied methyl jasmonate (MeJA) stimulated soyasaponin biosynthesis in cultured cells of Glycyrrhiza glabra (common licorice). mRNA level and enzyme activity of beta-amyrin synthase (bAS), an oxidosqualene cyclase (OSC) situated at the branching point for oleanane-type triterpene saponin biosynthesis, were up-regulated by MeJA, whereas those of cycloartenol synthase, an OSC involved in sterol biosynthesis, were relatively constant. Two mRNAs of squalene synthase (SQS), an enzyme common to both triterpene and sterol biosyntheses, were also up-regulated by MeJA. In addition, enzyme activity of UDP-glucuronic acid: soyasapogenol B glucuronosyltransferase, an enzyme situated at a later step of soyasaponin biosynthesis, was also up-regulated by MeJA. Accumulations of bAS and two SQS mRNAs were not transient but lasted for 7 d after exposure to MeJA, resulting in the high-level accumulation (more than 2% of dry weight cells) of soyasaponins in cultured licorice cells. In contrast, bAS and SQS mRNAs were coordinately down-regulated by yeast extract, and mRNA accumulation of polyketide reductase, an enzyme involved in 5-deoxyflavonoid biosynthesis in cultured licorice cells, was induced transiently by yeast extract and MeJA, respectively.

Publication Types: PMID: 12721381 [PubMed - indexed for MEDLINE]

102. New dihydrostilbene derivatives from the leaves of Glycyrrhiza glabra and evaluation of their antioxidant activity.

Biondi DM, Rocco C, Ruberto G.

Istituto del CNR di Chimica Biomolecolare, Sezione di Catania, Via del Santuario 110, I-95028 Valverde CT, Italy.

Five new prenylated dihydrostilbenes, alpha,alpha'-dihydro-3,5,4'-trihydroxy-4,5'-diisopentenylstilbene (1), alpha,alpha'-dihydro-3,5,3',4'-tetrahydroxy-4,5'-diisopentenylstilbene (2), alpha,alpha'-dihydro-3,5,4'-trihydroxy-5'-isopentenylstilbene (3), alpha,alpha'-dihydro-3,5,3'-trihydroxy-4'-methoxy-5'-isopentenylstilbene (4), and alpha,alpha'-dihydro-3,5,3',4'-tetrahydroxy-5'-isopentenyl stilbene (5), along with four known flavonoids, glabranin (6), pinocembrin, (7), licoflavone (8), and wighteone (9), were isolated from a lipid extract of the leaves of Sicilian Glycyrrhiza glabra. The structures of the compounds were elucidated by spectroscopic methods. The antioxidant activities of the crude extracts and the isolated compounds were tested.

Publication Types: PMID: 12713396 [PubMed - indexed for MEDLINE]

103. Isoliquiritigenin inhibits the growth of prostate cancer.

Kanazawa M, Satomi Y, Mizutani Y, Ukimura O, Kawauchi A, Sakai T, Baba M, Okuyama T, Nishino H, Miki T.

Department of Urology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan. motohiro@koto.kpu-m.ac.jp

OBJECTIVE: Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. In this study, we investigated the anti-tumor effect of isoliquiritigenin on prostate cancer in vitro.METHODS: DU145 and LNCaP prostate cancer cell lines were used as targets. We examined the effects of isoliquiritigenin on cell proliferation, cell cycle regulation and cell cycle-regulating gene expression. Further, we investigated the effects of isoliquiritigenin on the GADD153 mRNA and protein expression, and promoter activity.RESULTS: Isoliquiritigenin significantly inhibited the proliferation of prostate cancer cell lines in a dose-dependent and time-dependent manner. Fluorescence-activated cell sorting (FACS) analysis indicated that isoliquiritigenin induced S and G2/M phase arrest. Isoliquiritigenin enhanced the expression of GADD153 mRNA and protein associated with cell cycle arrest. Further, isoliquiritigenin stimulated transcriptional activity of GADD153 promoter dose-dependently.CONCLUSION: These findings suggest that isoliquiritigenin is a candidate agent for the treatment of prostate cancer and GADD153 may play an important role in isoliquiritigenin-induced cell cycle arrest and cell growth inhibition.

Publication Types: PMID: 12706007 [PubMed - indexed for MEDLINE]

104. Comparative antioxidant activity of individual herbal components used in Ayurvedic medicine.

Naik GH, Priyadarsini KI, Satav JG, Banavalikar MM, Sohoni DP, Biyani MK, Mohan H.

Radiation Chemistry and Chemical Dynamics Division, Bhabha Atomic Research Centre, Trombay, Mumbai-400085, India.

Four aqueous extracts from different parts of medicinal plants used in Ayurveda (an ancient Indian Medicine) viz., Momardica charantia Linn (AP1), Glycyrrhiza glabra (AP2), Acacia catechu (AP3), and Terminalia chebula (AP4) were examined for their potential as antioxidants. The antioxidant activity of these extracts was tested by studying the inhibition of radiation induced lipid peroxidation in rat liver microsomes at different doses in the range of 100-600 Gy as estimated by thiobarbituric acid reactive substances (TBARS). Of all these extracts, AP4 showed maximum inhibition in the TBARS formation and hence is considered the best antioxidant among these four extracts. The extracts were found to restore antioxidant enzyme superoxide dismutase (SOD) from the radiation induced damage. The antioxidant capacities were also evaluated in terms of ascorbate equivalents by different methods such as cyclic voltammetry, decay of ABTS(.-) radical by pulse radiolysis and decrease in the absorbance of DPPH radicals. The results were found to be in agreement with the lipid peroxidation data and AP4 showed maximum value of ascorbate equivalents. Therefore AP4, with high antioxidant activity, is considered as the best among these four extracts.

Publication Types: PMID: 12657303 [PubMed - indexed for MEDLINE]

105. Anti-acne effects of Oriental herb extracts: a novel screening method to select anti-acne agents.

Nam C, Kim S, Sim Y, Chang I.

Skin Reserach Institute, Pacific R&D Center, Yongin, Korea. cjnam@pacific.co.kr

The acne-therapeutic effects of Oriental herb extracts were investigated in terms of antichemotactic effect on polymorphonuclear leucocytes, antilipogenic actions, antibacterial activity against Propionibacterium acnes and resistance induction potency in the bacteria. The ethanol extract (0.01%) of Angelica dahurica markedly suppressed neutrophil chemotaxis, comparable to the effect of erythromycin (0.01%), whereas a strong antilipogenic effect was obtained with rhizoma coptidis (Coptis chinensis) extract (0.01%), leading to a higher efficacy than that of retinoic acid (0.01%). Interestingly, only Glycyrrhiza glabra showed a remarkable antibacterial activity against P. acnes, resulting in negligible induction of resistance, in comparison with a marked development of resistance in the bacteria treated with erythromycin. We suggest that an appropriate formulation containing A. dahurica, rhizoma coptidis and G. glabra could be helpful for the prevention and treatment of acne lesions. Copyright 2003 S. Karger AG, Basel

Publication Types: PMID: 12637783 [PubMed - indexed for MEDLINE]

106. A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for women's health.

Xu H, Fabricant DS, Piersen CE, Bolton JL, Pezzuto JM, Fong H, Totura S, Farnsworth NR, Constantinou AI.

UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois at Chicago, Chicago, Illinois, USA.

Traditional taxonomic methods of botanical identification that rely primarily on morphological observations cannot be used efficiently when only powdered plant materials are available. Thus, our objectives were to determine if we could apply a molecular approach to: a) produce unique DNA profiles that are characteristic of the species, and b) determine if the geographical area or time of collection influences these DNA profiles. Towards this end, random amplified polymorphic DNA (RAPD) analyses were performed on a number of botanicals currently used for women's health. The test materials included samples from three species each of the genera Cimicifuga (Actaea) and Trifolium, as well as samples of Vitex agnus-castus L., Glycyrrhiza glabra L., Gingko biloba L., Valeriana officinalis L., Angelica sinensis (Oliv.) Diels, Viburnum prunifolium L., Humulus lupulus L., Vaccinium macrocarpon Ait., Panax ginseng C.A. Mey. Cimicifuga racemosa (L.) Nutt. and Trifolium pratense L. are currently under clinical investigation in our basic research laboratories and medical clinic for the relief of post-menopausal symptoms. Characteristic profiles produced with the OPC-15 primer could distinguish the three Cimicifuga species: C. racemosa, C. americana and C. rubifolia. Similar results were obtained with the three Trifolium species: Trifolium pratense L., Trifolium incarnatum L., and Trifolium repens L. Accessions of cultivated T. pratense collected from the same field at different times, produced identical profiles. Accessions of Cimicifuga species collected from different geographical areas produced similar but not identical DNA profiles; however, species-specific DNA fragments were identified. These results demonstrate that RAPD analysis can be applied to distinguish species when only powdered material is available for testing. This methodology can be applied to identify species of commercial value regardless of collection time or geographic area.

Publication Types: PMID: 12587700 [PubMed - indexed for MEDLINE]

107. Chemical modification of glycyrrhizic acid as a route to new bioactive compounds for medicine.

Baltina LA.

Institute of Organic Chemistry Ufa Research Centre of RAS, 71 Prospect Oktyabrya, Ufa, 450054, Russian Federation. baltina@anrb.ru

Glycyrrhizic Acid (GL) is the major bioactive triterpene glycoside of licorice root (Glycyrrhiza Radix) extracts possessing a wide range of pharmacological properties (anti-inflammatory, anti-ulcer, anti-allergic, anti-dote, anti-oxidant, anti-tumor, anti-viral etc.). Official sources of GL are Glycyrrhiza glabra L. and Gl. uralensis Fish. (Leguminosae). The content of GL in licorice root is 2-24% of the dry weight. GL is one of the leading natural compounds for clinical trials of chronic active viral hepatitis and HIV infections (preparation Stronger Neo-Minophagen C, SNMC), and its monoammonium salt (glycyram, tussilinar) is used as an anti-inflammatory and anti-allergic remedy. The synthetic transformations of GL on carboxyl and hydroxyl groups were carried out to produce new bioactive derivatives for medicine. GL esters were produced containing fragments of bioactive acids (4-nitrobenzoic, cinnamic, salycilic, acetylsalycilic, nicotinic, isonicotinic). Bioactive amides of GL were synthesized using chloroanhydride technique and N,N'-diciclohexylcarbodiimide (DCC) method. The synthesis of acylthioureids and semicarbazones was carried out via the reaction of triacylisothiocianate of penta-O-acetyl-GL with primary amines and hydrazines. The chain of transformations of trichloranhydride of penta-O-acetyl-GL was made with the introduction of diazoketone groups in the molecule. A new group of GL derivatives to be triterpene glycopeptides was prepared by the activated esters method (N-hydrohysuccinimide-DCC or N-hydroxybenzotriazol-DCC) using alkyl (methyl, ethyl, propyl, butyl, tert-butyl) or benzyl (4-nitrobenzyl) esters of amino acids. The glycyrrhizyl analogs of the known immunostimulator, N-acetyl-muramoyldipeptide (MDP), were synthesized using Reagent Woodward K. A series of ureids and carbamates of GL was synthesized containing 5-amino-5-desoxy-D-xylopyranose units. The synthesis of 4-nitro-4-desoxy-glycosides, modified analogs of GL, was carried out by the oxidative splitting of the carbohydrate part of GL with NaIO(4). Triterpene 2-desoxy-D-glycosides, analogs of GL, were prepared by the glycal method in the presence of iodine-containing promoters or sulfonic acid cation-exchange resin KU-2-8 (H+) and LiBr. New anti-inflammatory and anti-ulcer agents were found among GL derivatives such as esters, amides, ureids, carbamates, thioureids and glycopeptides. GL glycopeptides are of interest as immunomodulators. Some of the chemically modified GL derivatives (salts, amides, glycopeptides) were potent HIV-1 and HIV-2 inhibitors in vitro. Preparation niglizin (penta-O-nicotinate of GL) was studied clinically as an anti-inflammatory agent and is of interest for studies as hepatoprotector and HIV inhibitor.

Publication Types: PMID: 12570715 [PubMed - indexed for MEDLINE]

108. Plant antimutagens and their mixtures in inhibition of genotoxic effects of xenobiotics and aging processes.

Alekperov UK.

Institute of Genetics, 155 Prospect Azadliq, 370106, Baku, Azerbaijan Republic.

The antimutagenic effect of the bioactive compounds from fruits of Morus alba L. (MA), Punica granatum L. (PG), Diospyros kaki L. (DK), Cydonia oblonga Mill. (CO) and roots of Glycyrrhiza glabra (GG) were investigated. The antimutagenic effects of compounds separately as well as their action in complex mixtures were studied on mutations induced by genotoxicants (X-rays, N-methylnitrosourea, cyclophosphamide, NaF) and aging in bone marrow cell chromosomes from mice and rats. When tested separately and in a complex mixture, the plant products showed an ability to decrease the frequency of chromosome aberrations. The antimutagenic properties of the complex mixtures were considerably greater than those of the separate components. More antimutagenic activity of the mixture was revealed when mutagenesis was the result of X-rays and the natural aging processes.

Publication Types: PMID: 12570329 [PubMed - indexed for MEDLINE]

109. The effect of glycyrrhizin on the release rate and skin penetration of diclofenac sodium from topical formulations.

Nokhodchi A, Nazemiyeh H, Ghafourian T, Hassan-Zadeh D, Valizadeh H, Bahary LA.

Department of Pharmacy, School of Health and Life Sciences, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NN, UK. nokhodchia@hotmail.com

The influence of glycyrrhizin extracted from Glycyrrhiza glabra var. glandulifera (licorice roots) on the percutaneous absorption of diclofenac sodium from sodium carboxymethylcellulose (NaCMC) gels or oil-in-water (o/w) emulsion was investigated. Skin permeation experiments were carried out using excised abdominal rat skin. The results showed that the efficiency of glycyrrhizin as an enhancer agent is greater in gel formulations than it is in the emulsions. The enhancer with the concentration of 0.1% w/w in gel increased diclofenac sodium flux value to tenfold compared with the control gel.

PMID: 12484536 [PubMed - indexed for MEDLINE]

110. Herbal medicines for liver diseases in India.

Thyagarajan SP, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi MS.

Department of Microbiology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India. sptrajan@md4.vsnl.net.in

The use of natural remedies for the treatment of liver diseases has a long history, starting with the Ayurvedhic treatment, and extending to the Chinese, European and other systems of traditional medicines. The 21st century has seen a paradigm shift towards therapeutic evaluation of herbal products in liver diseases by carefully synergizing the strengths of the traditional systems of medicine with that of the modern concept of evidence-based medicinal evaluation, standardization of herbal products and randomized placebo controlled clinical trials to support clinical efficacy. The present review provides the status report on the scientific approaches made to herbal preparations used in Indian systems of medicine for the treatment of liver diseases. In spite of the availability of more than 300 preparations for the treatment of jaundice and chronic liver diseases in Indian systems of medicine using more than 87 Indian medicinal plants, only four terrestrial plants have been scientifically elucidated while adhering to the internationally acceptable scientific protocols. In-depth studies have proved Sylibum marianum to be anti-oxidative, antilipidperoxidative, antifibrotic, anti-inflammatory, immunomodulating and liver regenerative. Glycyrrhiza glabra has been shown to be hepatoprotective and capable of inducing an indigenous interferon. Picrorhiza kurroa is proved to be anti-inflammatory, hepatoprotective and immunomodulatory. Extensive studies on Phyllanthus amarus have confirmed this plant preparation as being anti-viral against hepatitis B and C viruses, hepatoprotective and immunomodulating, as well as possessing anti-inflammatory properties. For the first time in the Indian systems of medicine, a chemo-biological fingerprinting methodology for standardization of P. amarus preparation has been patented. Copyright 2002 Blackwell Publishing Asia Pty Ltd

Publication Types:
PMID: 12472966 [PubMed - indexed for MEDLINE]

111. Antioxidant effect of licorice root on blood catalase activity in vibration stress.

Oganesyan KR.

Department of Human and Animal Physiology, Erevan State University, Armenia.

Rabbits were treated (orally) with a preparation of Glycyrrhiza glabra L. for 30 days and in parallel were exposed to vibration stress (30 days). The licorice preparation reduced catalase activity in the peripheral blood and increased animal resistance to vibration stress.

PMID: 12459833 [PubMed - indexed for MEDLINE]

112. Liquorice (Glycyrrhiza glabra) and the adrenal-kidney-pituitary axis in rats.

Al-Qarawi AA, Abdel-Rahman HA, Ali BH, El Mougy SA.

The effect of oral administration of a water freeze-dried extract of Glycyrrhiza glabra (liquorice) has been studied at doses of 100, 250 and 500 mg/kg in rats on the plasma concentration of cortisol, adrenocorticotrophic hormone (ACTH), aldosterone, renin, sodium (Na) and potassium (K). The results indicated that treatment induced dose-dependent and mostly significant decreases in the concentration of cortisol, ACTH, aldosterone and K. There were concomitant dose-dependent increases in the concentrations of renin and Na. The results suggest a strong and dose-dependent suppression of the adrenal-pituitary axis, accompanied by stimulation of renin production from the kidney.

PMID: 12387318 [PubMed - indexed for MEDLINE]

113. Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus.

Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T.

School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. fukai@pahr.toho-u.ac.jp

Nineteen flavonoids isolated from licorice (Glycyrrhiza glabra, G. inflata and G. uralensis) were tested for their antimicrobial activities against methicillin sensitive Staphylococcus aureus, methicillin resistant S. aureus, Micrococcus luteus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Copyright 2002 Elsevier Science B.V.

PMID: 12385884 [PubMed - indexed for MEDLINE]

114. Protection of DNA and microsomal membranes in vitro by Glycyrrhiza glabra L. against gamma irradiation.

Shetty TK, Satav JG, Nair CK.

Radiation Biology Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.

The radioprotective effect of the root extract of Glycyrrhiza glabra L on lipid peroxidation in rat liver microsomes and plasmid pBR322 DNA was investigated. The extract was found to protect microsomal membranes, as evident from reduction in lipid peroxidation, and could also protect plasmid DNA from radiation-induced strand breaks. Copyright 2002 John Wiley & Sons, Ltd.

Publication Types: PMID: 12237818 [PubMed - indexed for MEDLINE]

115. Immunological studies of Revitonil, a phytopharmaceutical containing Echinacea purpurea and Glycyrrhiza glabra root extract.

Wagner H, Jurcic K.

Department of Pharmacy, Center of Pharma Research, Institut of Pharmaceutical Biology, University of Munich, Germany. H.Wagner@cup.uni-muenchen.de

A phytopharmaceutical containing an extract of Echinacea purpurea and Glycyrrhiza glabra root (Revitonil tablets) was investigated for its suggested immunostimulating potential, using several in vitro tests and the in vivo carbon-clearance model in mice. In the in vitro phagocytosis test with human granulocytes, Revitonil showed a 44-53% stimulating effect at a concentration of 100 microg/ml. Whereas in the chemoluminescence test at a concentration of 1.25 microg/ml, Revitonil tablets exhibited a moderate enhancing effect only, a remarkable stimulating activity (30-50%) was observed in the T-lymphocyte CD69 bioassay at a concentration of 100 microg-1 microg/ml. The highest immunological efficacy could be assigned to Revitonil as revealed by the in vivo carbon-clearance model in mice. With RCt/RCc-values of 2.0, Revitonil exhibited a very high carbon elimination rate at oral administration. Because the Echinacea and Glycyrrhiza monoextracts alone showed lower RCt/RCc-values (1.3-1.7) than Revitonil, a potentiating synergistic effect of the extract mixture in Revitonil can be postulated.

Publication Types: PMID: 12222657 [PubMed - indexed for MEDLINE]

116. Anti-Helicobacter pylori flavonoids from licorice extract.

Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T.

Department of Physico-chemical Analysis, School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. fukai@phar.toho-u.ac.jp

Licorice is the most used crude drug in Kampo medicines (traditional Chinese medicines modified in Japan). The extract of the medicinal plant is also used as the basis of anti-ulcer medicines for treatment of peptic ulcer. Among the chemical constituents of the plant, glabridin and glabrene (components of Glycyrrhiza glabra), licochalcone A (G. inflata), licoricidin and licoisoflavone B (G. uralensis) exhibited inhibitory activity against the growth of Helicobacter pylori in vitro. These flavonoids also showed anti-H. pylori activity against a clarithromycin (CLAR) and amoxicillin (AMOX)-resistant strain. We also investigated the methanol extract of G. uralensis. From the extract, three new isoflavonoids (3-arylcoumarin, pterocarpan, and isoflavan) with a pyran ring, gancaonols A[bond]C, were isolated together with 15 known flavonoids. Among these compounds, vestitol, licoricone, 1-methoxyphaseollidin and gancaonol C exhibited anti-H. pylori activity against the CLAR and AMOX-resistant strain as well as four CLAR (AMOX)-sensitive strains. Glycyrin, formononetin, isolicoflavonol, glyasperin D, 6,8-diprenylorobol, gancaonin I, dihydrolicoisoflavone A, and gancaonol B possessed weaker anti-H. pylori activity. These compounds may be useful chemopreventive agents for peptic ulcer or gastric cancer in H. pylori-infected individuals.

PMID: 12127165 [PubMed - indexed for MEDLINE]

117. [Comparative study of Glycyrrhiza glabra L. and Glycyrrhiza echinata L. of different origin. Medicinal plant polysaccharides III]

[Article in Hungarian]

Gyémánt G, Lenkey B, Nánási P.

Debreceni Egyetem, Természettudományi Kar, Biokémiai Tanszék, Debrecen.

Comparative study was carried out among the polysaccharides of Chinese, Lithuanian and Hungarian origin Glycyrrhiza glabra L. as well as the Hungarian origin Glycyrrhiza echinata L. Monosaccharide composition, measured as alditol acetates, of Chinese and Hungarian G. glabra was very similar, but the Lithuanian G. glabra and the G. echinata were quite different. The monosaccharides of polysaccharides isolated from root and stem of G. echinata show significant differences (Table II.). All investigated samples contain glucuronic acid, the G. echinata contains also galacturonic acid (Table II.). Some fractions with higher uronic acid content and the acidic polysaccharides isolated from these fractions were studied and their monosaccharide composition was determined (Table III. and IV.).

Publication Types: PMID: 11961901 [PubMed - indexed for MEDLINE]

118. Novel polyphenol molecule isolated from licorice root (Glycrrhiza glabra) induces apoptosis, G2/M cell cycle arrest, and Bcl-2 phosphorylation in tumor cell lines.

Rafi MM, Vastano BC, Zhu N, Ho CT, Ghai G, Rosen RT, Gallo MA, DiPaola RS.

Department of Food Science and Center for Advanced Food Technology, Rutgers University, 65 Dudley Road, New Brunswick, New Jersey 08901-8520, USA.

Herbal therapies are commonly used by patients with cancer, despite little understanding about biologically active chemical derivatives. We recently demonstrated that the herbal combination PC-SPES, which contains licorice root, had anti-prostate cancer activity attributable to estrogen(s) that produced a chemical castration. A recent study also demonstrated that licorice root alone decreased circulating testosterone in men. Other studies demonstrated antitumor activity of PC-SPES in vitro associated with decreased expression of the anti-apoptotic protein Bcl-2 and in patients independent of chemical castration, suggesting that other mechanisms of antitumor activity exist separate from chemical castration. In the present study, we assessed licorice root extract for effects on Bcl-2 to identify novel cytotoxic derivatives. Licorice root extract induced Bcl-2 phosphorylation as demonstrated by immunoblot and G2/M cell cycle arrest, similarly to clinically used antimicrotubule agents such as paclitaxel. Bioassay-directed fractionations resulted in a biologically active fraction for Bcl-2 phosphorylation. HPLC separation followed by mass spectrometry and NMR identified 6 compounds. Only one molecule was responsible for Bcl-2 phosphorylation; it was identified as 1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4'-hydroxyphenyl) 1-propanone (beta-hydroxy-DHP). The effect on Bcl-2 was structure specific, because alpha-hydroxy-DHP, 1-(2,4-dihydroxyphenyl)-2-hydroxy-3-(4'-hydroxyphenyl) 1-propanone, in contrast to beta-hydroxy-DHP, was not capable of Bcl-2 phosphorylation. Pure beta-hydroxy-DHP induced Bcl-2 phosphorylation in breast and prostate tumor cells, G2/M cell cycle arrest, apoptosis demonstrated by Annexin V and TUNEL assay, decreased cell viability demonstrated by a tetrazolium (MTT) assay, and altered microtubule structure. Therefore, these data demonstrate that licorice root contains beta-hydroxy-DHP, which induced Bcl-2 phosphorylation, apoptosis, and G2/M cell cycle arrest, in breast and prostate tumor cells, similarly to the action of more complex (MW >800) antimicrotubule agents used clinically.

Publication Types: PMID: 11829627 [PubMed - indexed for MEDLINE]

119. Molecular cloning and characterization of isomultiflorenol synthase, a new triterpene synthase from Luffa cylindrica, involved in biosynthesis of bryonolic acid.

Hayashi H, Huang P, Inoue K, Hiraoka N, Ikeshiro Y, Yazaki K, Tanaka S, Kushiro T, Shibuya M, Ebizuka Y.

Gifu Pharmaceutical University, Japan. hayashih@gifu-pu.ac.jp

An oxidosqualene cyclase cDNA, LcIMS1, was isolated from cultured cells of Luffa cylindrica Roem. by heterologous hybridization with cDNA of Glycyrrhiza glabra beta-amyrin synthase. Expression of LcIMS1 in yeast lacking endogenous oxidosqualene cyclase activity resulted in the accumulation of isomultiflorenol, a triterpene. This is consistent with LcIMS1 encoding isomultiflorenol synthase, an oxidosqualene cyclase involved in bryonolic acid biosynthesis in cultured Luffa cells. The deduced amino-acid sequence of LcIMS1 shows relatively low identity with other triterpene synthases, suggesting that isomultiflorenol synthase should be classified into a new group of triterpene synthases. The levels of isomultiflorenol synthase and cycloartenol synthase mRNAs, which were measured with gene-specific probes, correlated with the accumulation of bryonolic acid and phytosterols over a growth cycle of the Luffa cell cultures. Isomultiflorenol synthase mRNA was low during the early stages of cell growth and accumulated to relatively high levels in the late stages. Induction of this mRNA preceded accumulation of bryonolic acid. In contrast, cycloartenol synthase mRNA accumulated in the early stages of the culture cycle, whereas phytosterols accumulated at the same relative rate throughout the whole growth cycle. These results suggest independent regulation of these two genes and of the accumulation of bryonolic acid and phytosterols.

PMID: 11733028 [PubMed - indexed for MEDLINE]

120. [Glabrizoflavone--a novel isoflavone from Glycyrrhiza glabra L.]

[Article in Russian]

Iuldashev MP, Batirov EKh, Vdovin AD, Abdullaev ND.

Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, prosp. Akademika Abdullaeva 77, Tashkent, 700170 Uzbekistan.

7-O-Methylglabranin, 6-C-prenylpinocembrin, glabranin, pinocembrin, galangin, and a novel isoflavonoid, (E)-5,7,4'-trihydroxy-6-(3-hydroxymethyl-2-butenyl)isoflavone (glabrisoflavone) were isolated from the aerial parts of Glycyrrhiza glabra L. The structure of the novel isoflavonoid was elucidated on the basis of chemical transformations and spectral data.

Publication Types: PMID: 11696898 [PubMed - indexed for MEDLINE]

121. Synergy and other interactions in phytomedicines.

Williamson EM.

The School of Pharmacy, University of London, United Kingdom. emwilliamson@enterprise.net

Synergistic interactions are of vital importance in phytomedicines, to explain difficulties in always isolating a single active ingredient, and explain the efficacy of apparently low doses of active constituents in a herbal product. This concept, that a whole or partially purified extract of a plant offers advantages over a single isolated ingredient, also underpins the philosophy of herbal medicine. Evidence to support the occurrence of synergy in within phytomedicines is now accumulating and is reviewed here. Synergistic interactions are documented for constituents within a total extract of a single herb, as well as between different herbs in a formulation. Positive and negative aspects of interactions are discussed together with the methods used to identify and measure synergy. The evidence is divided into experimental, in vitro instances, as well as clinical examples where available. Herbs discussed include Ginkgo biloba, Piper methysticum (Kava-Kava), Glycyrrhiza glabra, Hypericum perforatum, Valeriana officinalis, Cannabis sativa, Salix alba and others.

Publication Types: PMID: 11695885 [PubMed - indexed for MEDLINE]

122. Stimulation of melanogenesis by glycyrrhizin in B16 melanoma cells.

Jung GD, Yang JY, Song ES, Par JW.

Department of Dermatology, Presbyterian Medical Center, Chonju, Korea.

Glycyrrhizin (GR), triterpenoid saponin composed of one glycyrrhetinic acid (GA) and two glucuronic acids, is a main constituent of the hydrophilic fraction of licorice (Glycyrrhiza glabra) extracts and is known to have a wide range of pharmacological actions. In this study, we investigated the mechanism of GR effect on melanogenesis in B16 murine melanoma cells. The cellular levels of tyrosinase mRNA, protein, enzyme activities and melanin contents were increased by GR in a dose dependent manner. Expression of tyrosinase-related protein-2 (TRP-2) mRNA was also increased by GR, however, no significant change was observed on TRP-1. No cytotoxicity was observed at the effective concentration range of GR. GA showed no effect on melanogenesis at the equivalent nontoxic concentrations, indicating that glycoside structure is important in the stimulatory effect of GR on melanogenesis. These results indicate that GR-induced stimulation of melanogenesis is likely to occur through the transcriptional activation.

PMID: 11642548 [PubMed - indexed for MEDLINE]

123. Cloning and characterization of a cDNA encoding beta-amyrin synthase involved in glycyrrhizin and soyasaponin biosyntheses in licorice.

Hayashi H, Huang P, Kirakosyan A, Inoue K, Hiraoka N, Ikeshiro Y, Kushiro T, Shibuya M, Ebizuka Y.

Gifu Pharmaceutical University, Japan. hayashih@gifu-pu.ac.jp

An oxidosqualene cyclase cDNA, termed GgbAS1, was isolated from cultured cells of licorice (Glycyrrhiza glabra) by heterologous hybridization with cDNA of Arabidopsis thaliana LUP1 lupeol synthase. The yeast transformed with an expression vector containing the open reading frame of GgbAS1 produced beta-amyrin, indicating that GgbAS1 encodes beta-amyrin synthase involved in the glycyrrhizin and soyasaponin biosyntheses in licorice. Northern blot analysis showed that the level of beta-amyrin synthase mRNA was drastically changed in the cultured licorice cells, whereas the mRNA level of cycloartenol synthase was relatively constant.

Publication Types:

PMID: 11510484 [PubMed - indexed for MEDLINE]

124. Antiulcerogenic effect of some gastrointestinally acting plant extracts and their combination.

Khayyal MT, el-Ghazaly MA, Kenawy SA, Seif-el-Nasr M, Mahran LG, Kafafi YA, Okpanyi SN.

Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, Silybum marianum and Chelidonium majus, singly and combined in the form of a commercial preparation, STW 5 (Iberogast) and a modified formulation, STW 5-II, lacking the last 3 constituents, were tested for their potential anti-ulcerogenic activity against indometacin induced gastric ulcers of the rat as well as for their antisecretory and cytoprotective activities. All extracts produced a dose dependent anti-ulcerogenic activity associated with a reduced acid output and an increased mucin secretion, an increase in prostaglandin E2 release and a decrease in leukotrienes. The effect on pepsin content was rather variable and did not seem to bear a relationship with the anti-ulcerogenic activity. The most beneficial effects were observed with the combined formulations STW 5 and STW 5-II in a dose of 10 ml/kg b.w., comparable with cimetidine in a dose of 100 mg/kg b.w. The anti-ulcerogenic activity of the extracts was also confirmed histologically. The cytoprotective effect of the extracts could be partly due to their flavonoid content and to their free radical scavenging properties.

PMID: 11505785 [PubMed - indexed for MEDLINE]

125. Increases of secondary metabolite production in various plant cell cultures by co-cultivation with cork.

Yamamoto H, Yato A, Yazaki K, Hayashi H, Taguchi G, Inoue K.

Medicinal Plant Garden, School of Pharmaceutical Sciences, Nagasaki University, Japan.

Cork tissues increased secondary metabolite production of various plant cell cultures in a different manner from those of conventional elicitors. In Sophora flavescens and Glycyrrhiza glabra cultured cells, cork tissues increased the amounts of both lipophilic and hydrophilic flavonoids without affecting the cell growth, although elicitors such as copper ion and yeast extracts showed a clear inhibition of cell growth with the increasing amount of these lipophilic ones. The validity of this effect of cork tissues covered a wide range of aromatic compounds produced by suspension cell cultures derived from diverse plant species. Woody tissues of Japanese cypress had a very similar effect to that of cork. Partial purification of cork tissues suggested that the production-stimulating factor was present in the hemicellulose B fraction that was not included in the dedifferentiated cultured tissues.

PMID: 11388464 [PubMed - indexed for MEDLINE]

126. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms.

Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, Booth N, Constantinou AI, Pezzuto JM, Fong HH, Farnsworth NR, Bolton JL.

Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, M/C 781, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA.

Eight botanical preparations that are commonly used for the treatment of menopausal symptoms were tested for estrogenic activity. Methanol extracts of red clover (Trifolium pratense L.), chasteberry (Vitex agnus-castus L.), and hops (Humulus lupulus L.) showed significant competitive binding to estrogen receptors alpha (ER alpha) and beta (ER beta). With cultured Ishikawa (endometrial) cells, red clover and hops exhibited estrogenic activity as indicated by induction of alkaline phosphatase (AP) activity and up-regulation of progesterone receptor (PR) mRNA. Chasteberry also stimulated PR expression, but no induction of AP activity was observed. In S30 breast cancer cells, pS2 (presenelin-2), another estrogen-inducible gene, was up-regulated in the presence of red clover, hops, and chasteberry. Interestingly, extracts of Asian ginseng (Panax ginseng C.A. Meyer) and North American ginseng (Panax quinquefolius L.) induced pS2 mRNA expression in S30 cells, but no significant ER binding affinity, AP induction, or PR expression was noted in Ishikawa cells. Dong quai [Angelica sinensis (Oliv.) Diels] and licorice (Glycyrrhiza glabra L.) showed only weak ER binding and PR and pS2 mRNA induction. Black cohosh [Cimicifuga racemosa (L.) Nutt.] showed no activity in any of the above in vitro assays. Bioassay-guided isolation utilizing ER competitive binding as a monitor and screening using ultrafiltration LC-MS revealed that genistein was the most active component of red clover. Consistent with this observation, genistein was found to be the most effective of four red clover isoflavones tested in the above in vitro assays. Therefore, estrogenic components of plant extracts can be identified using assays for estrogenic activity along with screening and identification of the active components using ultrafiltration LC-MS. These data suggest a potential use for some dietary supplements, ingested by human beings, in the treatment of menopausal symptoms.

Publication Types: PMID: 11368622 [PubMed - indexed for MEDLINE]

127. In vitro anti-mycotic activity of some medicinal plants containing flavonoids.

Trovato A, Monforte MT, Forestieri AM, Pizzimenti F.

Pharmaco-Biological Department, School of Pharmacy, Vill. SS. Annunziata, 98168 Messina.

Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck), Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa canina L. and Ruta graveolens L. have been studied. The antimycotic activity was evaluated "in vitro" on strains of Candida albicans isolated from clinical samples obtained in the course of acute vaginitis.

PMID: 11213443 [PubMed - indexed for MEDLINE]

128. Flavonoid constituents from Glycyrrhiza glabra hairy root cultures.

Li W, Asada Y, Yoshikawa T.

School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.

An unusual biflavonoid named licoagrodin was isolated from the hairy root cultures of Glycyrrhiza glabra (Leguminosae) along with three prenylated retrochalcones, licoagrochalcones B, C, D, a prenylated aurone, licoagroaurone and four known prenylated flavonoids, licochalcone C, kanzonol Y, glyinflanin B and glycyrdione A. From the glycosidic fraction, a isoflavone glycoside, licoagroside A, and a maltol glycoside, licoagroside B were isolated together with four known isoflavone glycosides, two flavone C-glycosides, and three other glycosides. Their structures were elucidated on the basis of spectroscopic evidence.

Publication Types: PMID: 11140606 [PubMed - indexed for MEDLINE]

129. Antioxidant activity of parapharmaceutics containing natural inhibitors of free radical processes.

Konovalova GG, Tikhaze AK, Lankin VZ.

Laboratory of Biochemistry of Free Radical Processes, AL Myasnikov Institute of Cardiology, Russian Cardiology Research-and-Production Center, Russian Ministry of Health, Moscow.

The duration of lag phase of ascorbate-dependent free radical oxidation of endogenous polyenic lipids in rat liver and myocardium considerably increased after oral administration of lacrinat containing licorice Glycyrrhiza glabra root powder for 1 month. Lacrinat markedly decreased the content of lipid peroxides in rat liver. Ex vivo antioxidant effects of lacrinat in rat liver were comparable with those of beta-carotene-containing preparations carinat and carinat CD. Parapharmaceutics containing both licorice Glycyrrhiza glabra root powder and beta-carotene (carinat forte) markedly increased antioxidant activity of the liver.

PMID: 11140579 [PubMed - indexed for MEDLINE]

130. Biosynthesis of the dimethylallyl moiety of glabrol in Glycyrrhiza glabra hairy root cultures via a non-mevalonate pathway.

Asada Y, Li W, Yoshikawa T.

School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. asaday@pharm.kitasato-u.ac.jp

Incorporation of [1-13C]glucose indicates that the biosynthesis of the hemiterpene moiety of glabrol, the main prenylated flavanone in the hairy root cultures of Glycyrrhiza glabra, proceeds via a glyceraldehyde/pyruvate non-mevalonate pathway.

Publication Types: PMID: 11117880 [PubMed - indexed for MEDLINE]

131. [Medicinal plant preparations used as adjuvant therapeutics in experimental oncology]

[Article in Russian]

Razina TG, Zueva EP, Amosova EN, Krylova SG.

Tomsk Scientific Center, Siberian Division, Russian Academy of Medical Sciences, Russia.

Experiments on mice inoculated with metastasing Lewis lung carcinoma showed that the antitumor and antimetastatic effects of cyclophosphan (cyclophosphamide) are potentiated by the extracts of phytopreparations based on Baikal scullcap (Scutellaria baikalensis), rhodiola (Rhodiola rosea), common licorice (Glycyrrhiza glabra), and their principal acting components--baikalin, paratyrosol, and glycyrram.

Publication Types: PMID: 11109531 [PubMed - indexed for MEDLINE]

132. Pharmacological effects of urinary products obtained after treatment with saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic reaction.

Taniguchi C, Homma M, Takano O, Hirano T, Oka K, Aoyagi Y, Niitsuma T, Hayashi T.

Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.

To define the anti-allergic components in Saiboku-To, a herbal medicine for bronchial asthma, we examined the effects of 11 compounds found in post-administrative urine of Saiboku-To on concanavalin A-induced human lymphocyte blastogenesis in vitro and picryl chloride (PC)-induced mouse ear swelling in vivo. The urinary products of Saiboku-To were flavonoids and lignans derived from the constitutional herbs and their hydrogenated metabolites. Medicarpin derived from Glycyrrhiza glabra, magnolol and 8,9-dihydroxydihydromagnolol from Magnolia officinalis, baicalein, wogonin and oroxylin A from Suctellaria baicalensis inhibited lymphocyte blastogenesis in dose-dependent fashion with IC50 values ranging from 3.0 to 7.7 micrograms/mL, which corresponded to 20-100 times that of prednisolone IC50 (0.08 microgram/mL). Davidigenin, dihydrowogonin and dihydrooroxylin A, which are hydrogenated metabolites of liquiritigenin, wogonin and oroxylin A, respectively, had no or little effects on lymphocyte blastogenesis. Oral administration of Saiboku-To, medicarpin, baicalein, magnolol and baicalin (100 mg/kg), inhibited PC-induced ear swelling significantly by 23.5, 40.1, 30.5, 23.6 and 20.9%, respectively, though the effects were weaker than that of 5 mg/kg of prednisolone (52.9%). The results suggested that flavonoids and lignans tested in the present study were implicated in anti-asthmatic effect of Saiboku-To through suppression of type IV allergic reaction.

Publication Types:PMID: 11105563 [PubMed - indexed for MEDLINE]

133. Tyrosinase inhibitory activity of Bangladeshi indigenous medicinal plants.

Khanom F, Kayahara H, Tadasa K.

The United Graduate School of Agricultural Science, Gifu University, Japan.

The tyrosinase-inhibitory activity of 15 kinds of Bangladeshi medicinal plants was evaluated. Methanol extracts were prepared for screening tests, and other kinds of extracts were also studied for those with high activity. Swertia chirata, Piper nigrum, Glycyrrhiza glabra, Piper longam and Ocimum americanum were screened as highly inhibiting samples. Methanol was found to be the most efficient solvent for extracting the active compounds. The 50% tyrosinase-inhibitory concentration of the Glycyrrhiza glabra methanol extract was 21.2 microg/ml.

Publication Types: PMID: 11055404 [PubMed - indexed for MEDLINE]

134. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures.

Budzinski JW, Foster BC, Vandenhoek S, Arnason JT.

Ottawa-Carleton Institute of Biology, University of Ottawa, Ontario, Canada.

Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and 13 related pure plant compounds have been analyzed for their in vitro cytochrome P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate assay. Roughly 75% of the commercial products and 50% of the pure compounds showed significant inhibition of CYP3A4 metabolite formation. For each herbal product and pure compound exhibiting dose-dependency, the inhibition values were used to generate median inhibitory concentration (IC50) curves using linear regression. Among the commercial extracts, Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort), and Uncaria tomentosa (cat's claw) had the lowest IC50 values at < 1% full strength, followed by Echinacea angustifolia roots, Trifolium pratense (wild cherry), Matricaria chamomilla (chamomile), and Glycyrrhiza glabra (licorice), which had IC50 values ranging from 1%-2% of full strength. Dillapiol, hypericin, and naringenin had the lowest IC50 values among the pure plant compounds at < 0.5 mM; dillapiol was the most potent inhibitor at 23.3 times the concentration of the positive CYP3A4 inhibitor ketoconazole. Utilizing high-throughput screening methodologies for assessing CYP3A4 inhibition by natural products has important implications for predicting the likelihood of potential herbal-drug interactions, as well as determining candidates for further in-depth analyses.

Publication Types: PMID: 10969720 [PubMed - indexed for MEDLINE]

135. [Interactions between herbal medicines and drugs]

[Article in Czech]

Tůmová L.

Katedra farmakognozie Farmaceutické fakulty Univerzity Karlovy, Hradec Králové.

At present the use of medicaments of plant origin is on the increase. It is therefore necessary to take into consideration that there exist known as well as potential interactions between the medicament of the medicinal plant. The problematic plants include Echinacea, Allium cepa, Gingko biloba, Panax ginseng, as well as Hypericum perforatum, Valeriana officinalis, or Glycyrrhiza glabra. Its use should be limited, or completely excluded in the cases of simultaneous therapy with, e.g., warfarin, hepatotoxically acting medicaments, MAOI inhibitors, phenelzin sulphate, or phenytoin, as they may decrease of completely eliminate the therapeutic effect of the administered drugs, or they may cause a toxic damage to the organism.

Publication Types: PMID: 10953464 [PubMed - indexed for MEDLINE]

136. Phylogenetic relationship of six Glycyrrhiza species based on rbcL sequences and chemical constituents.

Hayashi H, Hosono N, Kondo M, Hiraoka N, Ikeshiro Y, Shibano M, Kusano G, Yamamoto H, Tanaka T, Inoue K.

Gifu Pharmaceutical University, Japan. hayashih@gifu-pu.ac.jp

The nucleotide sequences of ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) of Glycyrrhiza glabra, G. uralensis, G. inflata, G. echinata, G. macedonica and G. pallidiflora have been determined to construct their phylogenetic tree. Based on these sequences, the six Glycyrrhiza species were divided into two groups: three, G. glabra, G. uralensis, and G. inflata, which produce glycyrrhizin as a major saponin, and the others, G. echinata, G. macedonica and G. pallidiflora, which produce macedonoside C as a major saponin. Among the three glycyrrhizin-producing species, only two nucleotide substitutions were observed between the rbcL sequences of G. glabra and G. uralensis, and the sequence of G. uralensis was identical to that of G. inflata, indicating that G. uralensis and G. inflata are closely related. Among the three macedonoside C-producing species, only one nucleotide substitution was observed between those of G. echinata and G. macedonica, indicating that these two species are also closely related.

Publication Types: PMID: 10823673 [PubMed - indexed for MEDLINE]

137. Protection of mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra.

Haraguchi H, Yoshida N, Ishikawa H, Tamura Y, Mizutani K, Kinoshita T.

Faculty of Engineering, Fukuyama University, Japan.

Isoflavan derivatives, glabridin (1), hispaglabridin A (2), hispaglabridin B (3), 4'-Omethylglabridin (4) and 3'-hydroxy-4'-O-methylglabridin (5), isolated from Glycyrrhiza glabra, were investigated for their ability to protect liver mitochondria against oxidative stresses. Mitochondrial lipid peroxidation linked to respiratory electron transport and that induced non-enzymatically were inhibited by these isoflavans. Hispaglabridin A (2) strongly inhibited both peroxidations and 3'-hydroxy-4'-O-methylglabridin (5) was the most effective at preventing NADH-dependent peroxidation. 3'-Hydroxy-4'-O-methylglabridin (5) protected mitochondrial respiratory enzyme activities against NADPH-dependent peroxidation injury. Dihydroxyfumarate-induced mitochondrial peroxidation was also prevented by this isoflavan. Isoflavans from G. glabra were shown to be effective in protecting mitochondrial function against oxidative stresses.

PMID: 10714953 [PubMed - indexed for MEDLINE]

138. Molecular cloning and characterization of a cDNA for Glycyrrhiza glabra cycloartenol synthase.

Hayashi H, Hiraoka N, Ikeshiro Y, Kushiro T, Morita M, Shibuya M, Ebizuka Y.

Niigata College of Pharmacy, Japan.

A cDNA clone (GgCAS1) encoding cycloartenol synthase (CAS) has been isolated from Glycyrrhiza glabra (licorice) by cross-hybridization with that of Pisum sativum CAS as a probe. The deduced amino acid sequence of GgCAS1 exhibits 89%, 83% and 81% identity to those of Pisum sativum, Panax ginseng and Arabidopsis thaliana CASs, respectively. CAS activity has been detected in the homogenate of the yeast transformed with the expression vector containing the open reading frame of GgCAS1. Southern blot analysis suggested that at least two CAS genes exist in the licorice genome. In Northern blot analysis, the strong signal for CAS mRNA is detected in the cultured licorice cells of all growth phases, but no significant increase of CAS mRNA expression was observed in the cells treated with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, pravastatin.

Publication Types: PMID: 10706391 [PubMed - indexed for MEDLINE]

139. Herb-drug interactions.

Fugh-Berman A.

George Washington University School of Medicine and Health Sciences, Department of Health Care Sciences, Washington, DC 20037, USA. fughberman@aol.com

Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

Publication Types: PMID: 10675182 [PubMed - indexed for MEDLINE]

140. Molecular cloning and characterization of two cDNAs for Glycyrrhiza glabra squalene synthase.

Hayashi H, Hirota A, Hiraoka N, Ikeshiro Y.

Niigata College of Pharmacy, Japan.

Two cDNAs (GgSQS1 and GgSQS2) encoding squalene synthase have been isolated from licorice, Glycyrrhiza glabra L., and characterized. The deduced amino acid sequence of GgSQS1 was 88%, 81%, 78%, 45-44%, and 45-41% identical to those of GgSQS2, Nicotiana, Arabidopsis, mammal and yeast squalene synthases, respectively. Squalene synthase activity was found in the cell-free extracts of Escherichia coli transformed with the recombinant plasmids for GgSQS1 and GgSQS2, respectively. Genomic Southern blot hybridization indicated that there are three squalene synthase genes in the licorice genome. Northern blot analysis showed that GgSQS2 mRNA is mainly expressed during the exponential growth phase of the cultured licorice cells.

Publication Types: PMID: 10513618 [PubMed - indexed for MEDLINE]

141. A review of plants used in the treatment of liver disease: part two.

Luper S.

Southwest College of Naturopathic Medicine: 2140 East Broadway Rd. Tempe, AZ 85282, USA. lupers@cwix.com

Botanical medicines have been used traditionally by herbalists and indigenous healers worldwide for the prevention and treatment of liver disease. Clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease, while basic scientific research has uncovered the mechanisms by which some plants provide their therapeutic effects. This article is Part Two in a review of botanicals used in the treatment of liver disease. Curcuma longa (turmeric), Camellia sinensis (green tea), and Glycyrrhiza glabra (licorice) are reviewed in this installment. Silybum marianum (milk thistle) and Picrorhiza kurroa (kutkin) were reviewed in Part One.

Publication Types: PMID: 10383482 [PubMed - indexed for MEDLINE]

142. Antimicrobial flavonoids from Glycyrrhiza glabra hairy root cultures.

Li W, Asada Y, Yoshikawa T.

A new compound named licoagrodione was isolated from the hairy root cultures of Glycyrrhiza glabra (Fabaceae) together with five known prenylated flavonoids. The structure of licoagrodione has been elucidated on the basis of spectral evidence and it was found to have antimicrobial activity indicated by disc diffusion method.

Publication Types: PMID: 9933991 [PubMed - indexed for MEDLINE]

143. Activation of macrophages by crude polysaccharide fractions obtained from shoots of Glycyrrhiza glabra and hairy roots of Glycyrrhiza uralensis in vitro.

Nose M, Terawaki K, Oguri K, Ogihara Y, Yoshimatsu K, Shimomura K.

Department of Pharmacognosy and Plant Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.

Many plant polysaccharide fractions have been reported as immunomodulatory agents. However, sometimes the possibility of contamination with bacterial lipopolysaccharide (LPS), a potent B cell mitogen and immune modulator, is discussed. In the present paper, we investigated the effects of crude polysaccharide fractions obtained from the shoot and hairy root of Glycyrrhizae sp. on murine peritoneal macrophage function, in order to clarify whether plants grown under aseptic conditions produce immunomodulatory polysaccharides. All crude polysaccharide fractions induced nitric oxide production by murine peritoneal macrophages in vitro. Chemical analysis revealed that LPS-like molecules were not present in all preparations. These results suggested that shoot and hairy root biosynthesized polysaccharides that could stimulate macrophages de novo.

PMID: 9821821 [PubMed - indexed for MEDLINE]

[Polysaccharides of Glycyrrhiza glabra L. and Glycyrrhiza echinata L. Medicinal plants II]

[Article in Hungarian]

Kiss T, Gyémánt G, Dános B, Nánási P.

Kossuth Lajos Tudományegyetem Biokémiai Tanszék, Debrecen, Hungary.

Comparative study was carried out among the polysaccharides of Chinese, Lithuanian and Hungarian origin Glycyrrhiza glabra root samples as well as the Hungarian origin Glycyrrhiza echinata, which has not been studied earlier. The plant material was extracted with boiling water and the yield, the carbohydrate and the uronic acid content was measured by the alpha-naphtol and the Bitter method [21], respectively. Although the yield of Hungarian origin species was found lower than the yield of eastern species, the uronic acid content was similar. (Table I.) Our results show that to extract polysaccharides containing uronic acids needed longer extraction time, about 4 hours. The stem of Glycyrrhiza echinata might be useful from a practical point of view because of its large size and easy of access. (Table I. II.) Some fractions containing uronic acid in higher amount were separated on DEAE Sepharose CL-6B anion exchange column. After hydrolysis, reduction and acetylation the monosaccharide composition of this fractions was analysed by GC. (Table IV.).

Publication Types: PMID: 9805811 [PubMed - indexed for MEDLINE]

145. Seasonal variation of glycyrrhizin and isoliquiritigenin glycosides in the root of Glycyrrhiza glabra L.

Hayashi H, Hiraoka N, Ikeshiro Y, Yamamoto H, Yoshikawa T.

Niigata College of Pharmacy, Japan.

The time courses of the glycyrrhizin and isoliquiritigenin glycoside contents in the thickening roots of licorice, Glycyrrhiza glabra L., have been determined. The glycyrrhizin content in 1-year-old roots rapidly increased from October to November, whereas the isoliquiritigenin glycoside content increased up to October. In 3-year-old plants, although the isoliquiritigenin glycoside content rapidly increased from June to July, the glycyrrhizin content did not show any significant increase from May to August. The glycyrrhizin content increased during the senescence of the aerial parts as well as during the early stage of shoot elongation. The incorporation of [14C]mevalonic acid into the glycyrrhizin fraction by the root segments was high in May, June and September, and low in August and winter. These results indicated that the biosynthesis of glycyrrhizin is differently regulated from that of isoliquiritigenin glycoside in the thickening root of G. glabra.

Publication Types: PMID: 9781853 [PubMed - indexed for MEDLINE]

146. Phylogenetic relationship of Glycyrrhiza plants based on rbcL sequences.

Hayashi H, Hosono N, Kondo M, Hiraoka N, Ikeshiro Y.

Niigata College of Pharmacy, Japan.

The nucleotide sequences of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) of Glycyrrhiza glabra, G. uralensis, G. inflata, G. echinata, and G. pallidiflora have been determined to construct the phylogenetic tree. In the phylogenetic tree based on the rbcL sequences, the five Glycyrrhiza species were divided into two groups: the three glycyrrhizin-producing species G. glabra, G. uralensis, and G. inflata; and the two glycyrrhizin-nonproducing species G. echinata and G. pallidiflora. Among the three glycyrrhizin-producing species, only two nucleotide substitutions were observed between the rbcL sequence of G. glabra and G. uralensis, and the sequence of G. uralensis was identical to that of G. inflata, indicating that the three glycyrrhizin-producing species are closely related.

PMID: 9703269 [PubMed - indexed for MEDLINE]

147. Structural aspects of the inhibitory effect of glabridin on LDL oxidation.

Belinky PA, Aviram M, Mahmood S, Vaya J.

Laboratory of Natural Compounds for Medical Use, Migal, Galilee Technological Center, Kiryat Shmona, Israel.

The inhibitory effects of glabridin, an isoflavan isolated from licorice (Glycyrrhiza glabra) root, and its derivatives on the oxidation of LDL induced by copper ions or mediated by macrophages were studied, in order to evaluate the contribution of the different parts of the isoflavan molecule to its antioxidant activity. The peak potential (E1/2) of the isoflavan derivatives, their radical scavenging capacity toward 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and their ability to chelate heavy metals were also analyzed and compared to their inhibitory activity on LDL oxidation. In copper ion-induced LDL oxidation, glabridin (1), 4'-O-methylglabridin (2), hispaglabridin A (3), and hispaglabridin B (4), which have two hydroxyl groups at positions 2' and 4' or one hydroxyl at position 2' on ring B, successfully inhibited the formation of conjugated dienes, thiobarbituric acid reactive substances (TBARS) and lipid peroxides, and inhibited the electrophoretic mobility of LDL under oxidation. Compounds 1-3 exhibited similar activities, whereas compound 4 was less active. In macrophage-mediated LDL oxidation, the TBARS formation was also inhibited by these isoflavans (1-4) at a similar order of activity to that obtained in copper ion-induced LDL oxidation. On the other hand, 2'-O-methylglabridin (5), a synthesized compound, whose hydroxyl at 2'-position is protected and the hydroxyl at 4'-position is free, showed only minor inhibitory activity in both LDL oxidation systems. 2',4'-O-Dimethylglabridin (6), whose hydroxyls at 2'- and 4'-positions are both protected, was inactive. Resorcinol (7), which is identical to the phenolic B ring in glabridin, presented low activity in these oxidation systems. The isoflavene glabrene (8), which contains an additional double bond in the heterocyclic C ring, was the most active compound of the flavonoid derivatives tested in both oxidation systems. The peak potential of compounds 1-5 (300 microM), tested at pH 7.4, was similar (425-530 mV), and that for compound 6 and 8 was 1078 and 80 mV, respectively. Within 30 min of incubation, compounds 1, 2, 3, 4, 8 scavenged 31%, 16%, 74%, 51%, 86%, respectively, of DPPH radical, whereas compounds 5 and 6, which almost did not inhibit LDL oxidation, also failed to scavenge DPPH. None of the isoflavan derivatives nor the isoflavene compound were able to chelate iron, or copper ions. These results suggest that the antioxidant effect of glabridin on LDL oxidation appears to reside mainly in the 2' hydroxyl, and that the hydrophobic moiety of the isoflavan is essential to obtain this effect. It was also shown that the position of the hydroxyl group at B ring significantly affected the inhibitory efficiency of the isoflavan derivatives on LDL oxidation, but did not influence their ability to donate an electron to DPPH or their peak potential values.

PMID: 9641259 [PubMed - indexed for MEDLINE]

148. The antioxidative effects of the isoflavan glabridin on endogenous constituents of LDL during its oxidation.

Belinky PA, Aviram M, Fuhrman B, Rosenblat M, Vaya J.

Laboratory of Natural Compounds for Medical Use, Migal, Galilee Technological Center, Kiryat Shmona, Israel.

The effect of the consumption of glabridin, an isoflavan isolated from Glycyrrhiza glabra (licorice) root, on the susceptibility of low density lipoprotein (LDL) to oxidation was studied in atherosclerotic apolipoprotein E deficient (E[o] mice) and was compared with that of the known flavonoids, quercetin and catechin. Glabridin inhibitory activity on in vitro oxidation of human LDL was also investigated by determining the formation of lipid peroxides and oxysterols and the consumption of LDL-associated lipophilic antioxidants. Determination of the extent of LDL oxidation by measuring the formation of thiobabituric acid reactive substances (TBARS) after 2 h of LDL incubation with CuSO4 (10 microM) or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) (5 mM), revealed that glabridin or quercetin consumption resulted in a 53 and 54% reduction in copper ion induced oxidation, respectively, and a 95 and 83% reduction in AAPH induced LDL oxidation, respectively. No inhibition was obtained with consumption of catechin. About 80% of glabridin was found to bind to the LDL human particle. In the in vitro oxidation of LDL induced by AAPH (5 mM), glabridin inhibited the formation of TBARS, lipid peroxides and cholesteryl linoleate hydroperoxide (CLOOH) at all the concentrations tested (5-60 microM), while in oxidation induced by copper ions (10 microM), glabridin exhibited a pro-oxidant activity at concentrations lower than 20 microM, and a clear antioxidant activity at concentrations greater than 20 microM. Glabridin (30 microM) inhibited the formation of cholest-5-ene-3,7-diol (7-hydroxycholesterol), cholest-5-ene-3-ol-7-one (7-ketocholesterol) and cholestan-5,6-epoxy-3-ol (5,6-epoxycholesterol) after 6 h of AAPH induced LDL oxidation, by 55, 80 and 40%, respectively, and after 6 h of copper ion induced LDL oxidation, by 73, 94 and 52%, respectively. Glabridin also inhibited the consumption of beta-carotene and lycopene by 38 and 52%, respectively, after 0.5 h of LDL oxidation with AAPH, but failed to protect vitamin E. The in vivo and in vitro reduction of the susceptibility of LDL to oxidation obtained with glabridin, may be related to the absorption or binding of glabridin to the LDL particle and subsequent protection of LDL from oxidation by inhibiting the formation of lipid peroxides and oxysterols, and by protecting LDL associated carotenoids.

PMID: 9568736 [PubMed - indexed for MEDLINE]

149. Molecular characterization of tobacco squalene synthase and regulation in response to fungal elicitor.

Devarenne TP, Shin DH, Back K, Yin S, Chappell J.

Agronomy Department, University of Kentucky, Lexington 40546-0091, USA.

The enzyme squalene synthase (SS) represents the first commitment of carbon from the general isoprenoid pathway toward sterol biosynthesis and is a potential point for regulation of sterol biosynthesis. The isolation and characterization of tobacco (Nicotiana tabacum) squalene synthase (TSS) cDNA and genomic DNA clones, as well as determination of the steady state level of TSS mRNA in response to elicitor treatment, were investigated. cDNA clones for TSS were isolated from poly (A)+ RNA using a reverse transcription/polymerase chain reaction (RT/PCR) method. A 1233-bp cDNA clone was generated that contained an open reading frame of 411 amino acids giving a predicted molecular mass of 46.9 kDa. Comparison of the TSS deduced amino acid sequence with currently described SS from different species showed the highest identify with Nicotiana benthamiana (97%), followed by Glycyrrhiza glabra (81%), Arabidopsis thaliana (74%), rat (40%), and yeast (37%). Expression of a soluble form of the TSS enzyme with enzymatic activity in Escherichia coli was achieved by truncating 24 hydrophobic amino acids at the carboxy terminus. Characterization of genomic TSS (gTSS) revealed a gene of 7.086 kb with a complex organization of small exons and large introns not typical of plant genes. Southern blot hybridization indicated only two copies of the SS gene in the tobacco genome. Treatment of tobacco cell suspension cultures with a fungal elicitor dramatically reduced TSS enzymatic activity, lowering it to zero within 24 h. Analysis of TSS mRNA levels, by RNA blot hybridization and primer extension assays, in elicitor-treated cells indicated that the transcript level remained largely unchanged over this 24-h period. These results suggest that the suppression of TSS enzyme activity in elicitor-treated cells may result from a posttranscriptional modification of TSS.

Publication Types:
PMID: 9448707 [PubMed - indexed for MEDLINE]


150. Identification of glycyrrhizin as a thrombin inhibitor.

Francischetti IM, Monteiro RQ, Guimarăes JA.

Department of Medical Biochemistry, ICB/CCS, Federal University of Rio de Janeiro, Brazil.

Glycyrrhizin (GL), an anti-inflammatory compound isolated from Glycyrrhiza glabra, was identified as a new thrombin inhibitor: (a) It prolonged plasma recalcification and thrombin and fibrinogen clotting times, and (b) it inhibited thrombin-induced, but not collagen-, PAF- or convulxin-induced platelet aggregation. On the other hand, GL did not block thrombin's amidolytic activity upon S-2238. Furthermore, the fluorescence emission intensity of dansyl-thrombin was increased upon GL binding. Moreover, GL displaced hirudin as an inhibitor of thrombin-catalyzed hydrolysis of S-2238. Our data provide evidence that GL is a selective inhibitor of thrombin (the first one isolated from plants) that is able to exert its anti-thrombin action by interacting with the enzyme's anion binding exosite 1. A pharmacophoric search identified GL as a sialyl Lewis X (SLe[X]) mimetic compound able to inhibit selectin binding to SLe(X). However, SLe(X) did not affect thrombin clotting activities, which indicates a lack of its interaction with thrombin and distinguishes both molecules. It is suggested that the anti-inflammatory effect of GL may be due to its effective anti-thrombin action.

PMID: 9196073 [PubMed - indexed for MEDLINE]

151. In vitro antiviral activity of indigenous glycyrrhizin, licorice and glycyrrhizic acid (Sigma) on Japanese encephalitis virus.

Badam L.

National Institute of Virology, Pune, India.

Glycyrrhizin, a triterpenoid glycoside and Licorice from Glycyrrhiza glabra and Ammonium salt of Glycyrrhizic acid (Sigma) were tested for antiviral activity on three strains of Japanese encephalitis virus (JEV), Nakayama, P-20778 and 821564 XY48. Purified glycyrrhizin (M.w. 822.92) inhibited plaque formation in all the three strains of JEV at a concentration of 500 micrograms/ml at 96 hrs, Similar effect was observed at 1000 micrograms/ml concentration with Licorice and Ammonium salt of glycyrrhizic acid. The minimal inhibitory concentrations were not toxic to porcine stable kidney (PS) and human cervical carcinoma (HeLa) cell lines. Cyctotoxicity of these chemicals was evaluated by trypan blue dye exclusion test which indicated subtoxic concentrations at 5,000 micrograms/ml at 96 hrs and toxic concentrations were 10,000 micrograms/ml at the same time period for the host cells PS. Thus the indigenously purified glycyrrhizin seems to be more potent antiviral agent than Licorice and ammonium salt of glycyrrhizic acid (Sigma) for JEV 'in vitro'.

PMID: 9282507 [PubMed - indexed for MEDLINE]

152. Systematic analysis of post-administrative saiboku-to urine by liquid chromatography to determine pharmacokinetics of traditional Chinese medicine.

Homma M, Oka K, Taniguchi C, Niitsuma T, Hayashi T.

Department of Clinical Pharmacology, Tokyo University of Pharmacy & Life Science, Japan.

To disclose the mystery of a traditional Chinese medicine and to identify biologically active components, we analysed post-administrative urine for Saiboku-To, an anti-asthmatic Chinese herbal remedy. Systematic analysis of the components appearing in the urine was carried out by high-performance liquid chromatography (HPLC) with normal- and reversed-phase modes in combination. beta-D-glucuronidase-treated urine was subjected to rapid-flow fractionation (RFF) to achieve fractional extraction of lipophilic components with exhaustive recovery rates. The extracts were analysed by HPLC equipped with a multi-channel UV-detector. In the first stage of HPLC, we conducted a normal-phase mode run to find magnolol derived from Magnolia officinalis, as the most hydrophobic component showing minimum retention time among the urinary products of Saiboku-To. In the next stage, mobile phase solvent composition for reversed-phase HPLC was optimized so as to retain magnolol up to 60 min. Under these conditions, other Saiboku-To urinary products, which were more polar than magnolol, appeared within 60 min. Our HPLC method used marker compounds like magnolol and could indicate the terminal peak position on the reversed-phase chromatography. We found a total of eight components in the post-administrative Saiboku-To urine. Structure identification of the isolated pure materials was achieved using nuclear magnetic resonance (NMR)-, mass (MS)- and UV-spectra, and HPLC retention profiles. They were magnolol and 8,9-dihydroxydihydromagnolol stemming from M. officinalis, medicarpin and liquiritigenin from Glycyrrhiza glabra, baicalein, wogonin, and oroxylin A from Scutellaria baicalensis, and davidigenin of an unknown origin. The pharmacological mystery of Saiboku-To should be disclosed by resolving the pharmacokinetics and pharmacodynamics of these urinary products independently and synergistically.

Publication Types: PMID: 9192103 [PubMed - indexed for MEDLINE]

153. Effect of Glycyrrhiza glabra roots and glycyrrhizin on the glucuronidation in rats.

Moon A, Kim SH.

College of Pharmacy, Duksung Women's University, Seoul, Korea.

As an approach to elucidate the possible in vivo interaction of synthetic drugs and herbs which are frequently used in combination in Asia, the effect of Glycyrrhiza glabra on the metabolism of acetaminophen (AAP) was examined in male Sprague-Dawley rats. The pretreatment of the methanol extract of Glycyrrhiza glabra roots (Glycyrrhizae Radix, GR, 1 g/kg, p.o.) for 6 days significantly increased the cumulative biliary (156%) and urinary (132%) excretions of AAP-glucuronide conjugate within 120 min after the administration of AAP (150 mg/kg, i.v.) without affecting thioether and sulfate conjugates. These findings suggest that GR might enhance the glucuronidation pathway of AAP. In order to study the effect of GR on the glucuronidation in rat liver, we examined enzymatic activity of p-nitrophenol UDP-glucuronosyltransferase (UGT), which is also called UGT1A, and intracellular concentrations of hepatic UDP-glucuronic acid, upon the administration of GR (1 g/kg, p.o.) or glycyrrhizin (23 mg/kg, p.o.), a major component of GR, for 6 days. GR and glycyrrhizin caused increases in specific activities of UGT1A by 111% and 96%, respectively. Concentration of UDP-glucuronic acid was increased 257% by GR and 484% by glycyrrhizin. These data indicate that GR and glycyrrhizin activated glucuronidation and thus suggest the possibility that GR may influence detoxification of xenobiotics in rat liver. Using the p-nitrophenol UGT1A1 cDNA as a probe, we found that the activation of UGT1A by GR was not due to the induction of mRNAs for the enzyme.

PMID: 9140223 [PubMed - indexed for MEDLINE]

154. Antioxidant constituents from licorice roots: isolation, structure elucidation and antioxidative capacity toward LDL oxidation.

Vaya J, Belinky PA, Aviram M.

Migal, Galilee Technological Center, Kiryat Shmona, Israel.

The present study analyzed the antioxidative properties of natural compounds from the root of the plant Glycyrrhiza glabra (licorice) toward LDL oxidation. Seven constituents, with antioxidant capacity were isolated from Glycyrrhiza glabra. The isolated compounds were identified as the isoflavans Hispaglabridin A (1), Hispaglabridin B (4), Glabridin (3), and 4'-O-Methylglabridin (2), the two chalcones, isoprenylchalcone derivative (5) and Isoliquiritigenin (6), and the isoflavone, Formononetin (7). Among these compounds, Glabridin constituted the major amount in the crude extract (11.6%, w/w) as detected by high-performance liquid chromatography (HPLC) analysis. The antioxidative capacities of the isolated compounds (1-7) were tested against beta-carotene destruction and LDL oxidation. The isoflavans (1-4) at a concentration of 50 microM inhibited beta-carotene consumption, following 90 min of incubation at 50 degrees C, similar to the inhibitory effect of the whole licorice crude extract (at 16 mg/1). The chalcones (5 and 6) exhibited moderate inhibition and the isoflavone 7 was almost inactive, whereas vitamin E (50 microM) completely inhibited beta-carotene consumption. The inhibitory effect of the constituents 1-7, at a concentration of 30 microM on 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced LDL oxidation was determined by measuring the amount of the thiobarbituric acid reactive substances (TBARS) and the amount of lipid peroxides. While compounds 1-6 exhibited high inhibitory activity, compound 7 and vitamin E were not active. A dose-dependent inhibitory effect of Glabridin, on the formation of cholesteryl linoleate hydroperoxide (CLOOH), in an AAPH-induced LDL oxidation system was also shown. Glabridin, at 5 or 40-60 microM concentration, inhibited the CLOOH formation by 62% and 90%, respectively. These results suggest that constituents 1-6 are very potent antioxidants toward LDL oxidation with Glabridin being the most abundant and potent antioxidant. As LDL oxidation is a key event in the formation of the early atherosclerotic lesion, the use of these natural antioxidants may be proven beneficial to attenuate atherosclerosis.

Publication Types: PMID: 9199893 [PubMed - indexed for MEDLINE]
155. Inhibition of human complement by beta-glycyrrhetinic acid.

Kroes BH, Beukelman CJ, van den Berg AJ, Wolbink GJ, van Dijk H, Labadie RP.

Research Centre for Natural Products and Phytopharmaceuticals, Faculty of Pharmacy, University of Utrecht, The Netherlands.

Licorice, the root extract of Glycyrrhiza glabra I., is used as a medicine for various diseases. Anti-inflammatory as well as anti-allergic activities have been attributed to one of its main constituents, glycyrrhizin. These activities are mainly ascribed to the action of the aglycone, beta-glycyrrhetinic acid. beta-Glycyrrhetinic acid has a steroid-like structure and is believed to have immunomodulatory properties. To determine whether interference with complement functions may contribute to the immunomodulatory activity of beta-glycyrrhetinic acid, its effects on the classical and alternative activation pathways of human complement were investigated. We found that beta-glycyrrhetinic acid is a potent inhibitor of the classical complement pathway (IC50 = 35 microM), whereas no inhibitory activity was observed towards the alternative pathway (IC50 > 2500 microM). The anticomplementary activity of beta-glycyrrhetinic acid was dependent on its conformation, since the alpha-form was not active. It was also established that naturally occurring steroids, e.g. hydrocortisone and cortisone, did not inhibit human complement activity under similar conditions. Detailed mechanistic studies revealed that beta-glycyrrhetinic acid acts at the level of complement component C2.

PMID: 9038721 [PubMed - indexed for MEDLINE]PMCID: PMC1456728

156. Molecular cloning and functional expression of cDNAs for Glycyrrhiza glabra squalene synthase.

Hayashi H, Hiraoka N, Ikeshiro Y.

Niigata College of Pharmacy, Japan.

We have isolated two cDNAs (GgSQS1 and GgSQS2) encoding squalene synthase of Glycyrrhiza glabra L. by cross-hybridization with that of Arabidopsis thaliana squalene synthase under conditions of low stringency. Their nucleotide sequences contained an open reading frame for a polypeptide of 413 amino acids (GgSQS1) and 412 amino acids (GgSQS2), respectively. The deduced amino acid sequence of GgSQS1 exhibits 88%, 81%, 78%, 45-44%, and 45-41% identity to those of the GgSQS2, Nicotiana benthamiana. Arabidopsis thaliana, mammal, and yeast squalene synthases, respectively. To express the G. glabra enzymes in Escherichia coli, the entire coding region was subcloned into an expression vector. The cell-free extracts of E.coli transformed with the respective plasmid converted 3H-farnesyl diphosphate into squalene.

Publication Types: PMID: 8913521 [PubMed - indexed for MEDLINE]

157. [Serious plant poisonings in Switzerland 1966-1994. Case analysis from the Swiss Toxicology Information Center]

[Article in German]

Jaspersen-Schib R, Theus L, Guirguis-Oeschger M, Gossweiler B, Meier-Abt PJ.

Schweizerisches Toxikologisches Informationszentrum (STIZ), Zürich.

AIM: To analyze the types, frequency and severity of plant poisonings in Switzerland over 29 years. METHODS: Retrospective analysis of severe poisonings with toxic plants reported to the Swiss Toxicological Information Center (STIC). Assessment of the causality, severity of symptoms and the types of plants involved. RESULTS: During the period under review the STIC registered 24 950 cases of contact with or ingestion of toxic plant material. In 99.4% of all cases the clinical course was either unknown, asymptomatic or associated with only minor symptoms (no hospitalization). Severe plant poisonings occurred in 152 cases. Detailed analysis was possible in 135 cases (23 children, 112 adults) including 5 lethal cases (all adults). The 24 plants involved produced the following severe symptoms: Atropa belladonna (42 cases): anticholinergic syndrome (42), acute psychosis (33), convulsions (2), coma (2). Heracleum mantegazzianum (18): severe photodermatitis (18). Datura stramonium (17): anticholinergic syndrome (17), psychosis (12), coma (2). Dieffenbachia (11): severe stomatitis (8), corneal lesions (3). Colchicum autumnala (10): diarrhea (10), liver necrosis (9), fatal multiorgan failure (2). Veratrum album (8): bradycardia ( < or = 40/min) (6), shock (5). Aconitum napellus (4): tachyarrhythmia (2), AV-block II/III (2). Aesculus hippocastanum (3): allergy (3), anaphylactic shock (2). Hyoscyamus niger (3): anticholinergic syndrome (3). Ricinus communis (3): diarrhea (3), toxic megacolon (1). Oenanthe crocata (2): convulsions (1), lethal coma (1). Taxus baccata (2): tachyarrhythmia (1), fatal asystole (1). Further single cases with severe poisonings were observed with Arum maculatum, Asarum europaeum, Chrysanthemum vulgare, Cyclamen persicum, Datura suaveolens, Glycyrrhiza glabra, Laburnum anagyroides, Lycopodium, Narcissus pseudonarcissus (lethal aspiration), Nerium oleander, Senecio vulgaris and Vicia faba. CONCLUSIONS: Potential and real intoxications with plant materials occurred in 7.2% of all cases registered at the STIC. However, among all plant cases only 0.6% were severe intoxications requiring hospitalization. Although severe plant intoxications are rare events, a small number of specific plants appear to be mainly responsible for continued serious plant poisoning in Switzerland. The present study has identified the plants with the highest toxicological risks and provides a data base for more rational prevention, diagnosis and treatment of plant poisoning cases in the future.

Publication Types: PMID: 8711457 [PubMed - indexed for MEDLINE]

158. In vitro cytotoxic effect of some medicinal plants containing flavonoids.

Trovato A, Monforte MT, Rossitto A, Forestieri AM.

Pharmaco-Biological Department, School of Pharmacy, Messina, Italy.

Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck), Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa canina L. and Ruta graveolens L. have been studied. The cytotoxicity of the drugs assayed was evaluated "in vitro" by means of the dye test using cells of the Yoshida ascites sarcoma. The aqueous extract of Citrus sinensis L. (Osbeck); the petroleum ether extract of Glycyrrhiza glabra L.; the ethanolic and petroleum ether extracts of Rosa canina L. and the petroleum ether extract of Ruta graveolens L. showed a quite significative cytotoxic effect.

PMID: 8913055 [PubMed - indexed for MEDLINE]

159. [The choleretic effects of licorice: identification and determination of the pharmacologically active components of Glycyrrhiza glabra]

[Article in Italian]

Raggi MA, Bugamelli F, Nobile L, Curcelli V, Mandrioli R, Rossetti A, Cantelli Forti G.

Dipartimento di Scienze Farmaceutiche, Universitŕ di Bologna.

Recent studies indicate that licorice extract, when administered per os or i.v., causes an evident choleretic effect in rats. Aim of this research is to identify and quantify those licorice constituents which are responsable for the observed choleresis. The quali-quantitative analysis of umbelliferon (7-idroxycoumarin), was at first performed by a fluorimetric method, subsequently by a more selective HPLC method. Moreover, this HPLC method allows the determination of glycyrrhizin, an important licorice constituent. Unlike the glycyrrhizin, which is present in a fairly large amount, umbelliferon resulted to be present at a very low concentration (at trace level), both in licorice and in bile. Research is in progress, aiming to determine the substances, beyond glycyrrhizin, which are responsable for the choleretic effect of licorice.

Publication Types: PMID: 8820979 [PubMed - indexed for MEDLINE]

160. Genetic relationships among Glycyrrhiza plants determined by RAPD and RFLP analyses.

Yamazaki M, Sato A, Shimomura K, Saito K, Murakoshi I.

Faculty of Pharmaceutical Sciences, Laboratory of Molecular Biology and Biotechnology, Chiba University, Japan.

The genetic similarities of four species of Glycyrrhiza plants were determined by DNA analyses of random amplified polymorphic DNA (RAPD) and restriction fragment length polymorphism (RFLP). The phylogenic trees were constructed from the genetic similarities estimated from RAPD and RFLP profiles. These results indicated that G. glabra and G. uralensis, rich in glycyrrhizin, are more closely related to each other than to G. echinata or to G. pallidiflora.

Publication Types: PMID: 7703980 [PubMed - indexed for MEDLINE]

161. Chemical studies of Chinese licorice-roots. I. Elucidation of five new flavonoid constituents from the roots of Glycyrrhiza glabra L. collected in Xinjiang.

Kitagawa I, Chen WZ, Hori K, Harada E, Yasuda N, Yoshikawa M, Ren J.

Faculty of Pharmaceutical Sciences, Osaka University, Japan.

From the air-dried roots of Glycyrrhiza glabra L. (Leguminosae) collected in Xinjiang province, China ("Shinkyo-Kanzo" in Japanese), five new flavonoid compounds named glucoliquiritin apioside (1) (a flavonone bisdesmoside), prenyllicoflavone A (5) (a bisprenylflavone), shinflavone (7) (a prenylated pyranoflavanone), shinpterocarpin (9) and 1-methoxyphaseollin (12) (both pyranopterocarpans), were isolated together with eight known saponins, seven known flavonoid glycosides, and eleven flavonoids. The structures of the new compounds have been elucidated on the basis of their chemical and physicochemical properties.

PMID: 8069956 [PubMed - indexed for MEDLINE]

162. A novel 11 beta-hydroxysteroid dehydrogenase inhibitor contained in saiboku-to, a herbal remedy for steroid-dependent bronchial asthma.

Homma M, Oka K, Niitsuma T, Itoh H.

Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.

To identify the inhibitor of prednisolone metabolism contained in Saiboku-To, we conducted in-vitro experiments of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), using rat liver homogenate and cortisol as a typical substrate. We studied the effects of ten herbal constituents on 11 beta-HSD. Five herbal extracts showed inhibitory activity with Glycyrrhiza glabra > Perillae frutescens > Zizyphus vulgaris > Magnolia officinalis > Scutellaria baicalensis. This suggests that unknown 11 beta-HSD inhibitors are contained in four herbs other than G. glabra which contains a known inhibitor, glycyrrhizin (and glycyrrhetinic acid). Seven chemical constituents which have been identified as the major urinary products of Saiboku-To in healthy and asthmatic subjects were studied; magnolol derived from M. officinalis showed the most potent inhibition of the enzyme (IC50, 1.8 x 10(-4) M). Although this activity was less than that of glycyrrhizin, the inhibition mechanism (non-competitive) was different from a known competitive mechanism. These results suggest that magnolol might contribute to the inhibitory effects of Saiboku-To on prednisolone metabolism through inhibition of 11 beta-HSD.

Publication Types: PMID: 8051615 [PubMed - indexed for MEDLINE]

163. Licorice ingestion and blood pressure regulating hormones.

Schambelan M.

Department of Medicine, San Francisco General Hospital, University of California 94110.

Nearly half a century ago Revers reported that administration of a paste prepared from succus liquiritiae, a dried watery extract of the roots of Glycyrrhiza glabra, resulted in a reduction in abdominal symptoms as well as radiographic evidence of healing in patients suffering from gastric ulcer. Subsequent studies demonstrated that this preparation could prevent the formation of gastric ulcers in experimental animals and confirmed the salutary effects in patients, but found that approximately 20% of patients so treated developed facial and dependent edema, often accompanied by headache, shortness of breath, stiffness, and pain in the upper abdomen. Although these symptoms suggested an allergic reaction, they were not accompanied by eosinophilia or relieved by antihistamines. These untoward effects usually subsided with a reduction of dose, although in some patients treatment had to be discontinued entirely. Given this profile of side effects, enthusiasm for licorice as a remedy for peptic ulcer disease soon faded. However, the popularity of licorice flavoring in candy and in other products such as chewing tobacco persists to this day, as do the problems in electrolyte and blood pressure homeostasis that can occasionally occur in individuals ingesting large quantities of licorice-containing products. Although the pattern of the renal response suggested that the active ingredients in licorice were acting directly on the mineralocorticoid receptors in the kidney, an even more fascinating explanation for the toxic effects of licorice has emerged in the past decade.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types: PMID: 8191541 [Pubed - indexed for MEDLINE]

164. Inhibition of mutagenicity in Salmonella typhimurium by Glycyrrhiza glabra extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids.

Zani F, Cuzzoni MT, Daglia M, Benvenuti S, Vampa G, Mazza P.

Dipartimento Farmaceutico, Facoltŕ di Farmacia, Universitŕ di Parma, Italy.

The effects of Glycyrrhiza glabra L. extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids on the mutagenicity of the ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and ribose-lysine Maillard model systems were investigated by using the Salmonella/microsome reversion assay. The protocol used allowed us to detect desmutagenic and antimutagenic activity and to avoid false positive results due to toxicity. For all the compounds tested, no desmutagenic activity was observed against ethyl methanesulfonate and N-methyl-N'-nitro-N-nitrosoguanidine; only Glycyrrhiza glabra extract showed antimutagenic activity against ethyl methanesulfonate. On using the ribose-lysine mutagenic browning mixture, the desmutagenic activities of the Glycyrrhiza glabra extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids were observed. 18 beta-Glycyrrhetinic acid was the most active compound. Glycyrrhiza glabra extract also exhibited antimutagenic activity against ribose-lysine.

PMID: 8302947 [PubMed - indexed for MEDLINE]

165. Distribution Pattern of Saponins in Different Organs of Glycyrrhiza glabra.

Hayashi H, Fukui H, Tabata M.

Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida, Kyoto 606, Japan.

Soyasaponins were detected by GC and GC-MS in different organs of GLYCYRRHIZA GLABRA, particularly in the seed, hypocotyl and rootlet, whereas glycyrrhizin was detected exclusively in the thickening root and the stolon. An inverse relationship was found between the soyasaponins content and the glycyrrhizin content in the growing stolon and in the roots at different stages of growth.

PMID: 17235989 [PubMed - in process]

166. A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure.

Acharya SK, Dasarathy S, Tandon A, Joshi YK, Tandon BN.

Department of Gastroenterology & Human Nutrition, All India Institute of Medical Sciences, New Delhi.

The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC) derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for 30 days followed by thrice weekly intravenously for 8 wk in 18 patients of subacute hepatic failure due to viral hepatitis. The survival rate amongst these patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per cent in 98 patients who received supportive therapy (P < 0.01). Death in four of the five patients was due to associated infections leading to hepatorenal failure and terminal coma. Further studies are necessary to standardize the dose and duration of therapy with SNMC in subacute hepatic failure.

Publication Types: PMID: 8344734 [PubMed - indexed for MEDLINE]

167. Extracellular interception of mutagens.

Shankel DM, Kuo S, Haines C, Mitscher LA.

Department of Microbiology, University of Kansas, Lawrence 66045.

Extracellular interception of mutagens by excreted enzymes or by chemical agents that react with or bind to formed mutagens provides an important means of defense against chemical mutagens/carcinogens. Kada and Shimoi have classified molecules that function in this manner as "desmutagens," and many of them are natural cellular metabolites. Among the specific mechanisms that such agents may employ are: prevention of the activation of "promutagens" to mutagens; stimulation of enzymes (e.g., glutathione-S-transferase) that catalyze the binding/inactivation of damaging electrophiles; direct binding and concomitant inactivation of promutagens or mutagens; interference with uptake of mutagens into cells; etc. De Flora and Ramel have provided an excellent discussion of the mechanisms of these agents and a proposed classification scheme. Drawing on work from our own laboratories and other recent examples in the literature, several examples of mechanistic approaches to these studies using natural plant-derived materials, e.g., humic acid, Glycyrrhiza glabra extract, glutathione, and bioflavonoids, are also described. Antioxidants and agents that conjugate electrophiles will be among the modes of action described for obtaining the goal of intercepting mutagens/carcinogens.

Publication Types: PMID: 8304956 [PubMed - indexed for MEDLINE]

168. Core structure of glycyrrhizan GA, the main polysaccharide from the stolon of Glycyrrhiza glabra var. glandulifera; anti-complementary and alkaline phosphatase-inducing activities of the polysaccharide and its degradation products.

Takada K, Tomoda M, Shimizu N.

Kyoritsu College of Pharmacy, Tokyo, Japan.

The controlled Smith degradation and limited hydrolysis of glycyrrhizan GA, a representative polysaccharide with remarkable phagocytosis-enhancing activity isolated from the stolon of Glycyrrhiza glabra L. var. glandulifera Reg. et Herd. were carried out. Methylation analyses of the primary and the secondary Smith degradation products and of the limited hydrolysis product indicated that the core structural features of glycyrrhizan GA include a backbone chain composed of beta-1,3-linked D-galactose residues. Three-fifths of the galactose units in the backbone carry side chains composed of beta-1,3- and beta-1,6-linked D-galactosyl residues at position 6. Anti-complementary and alkaline phosphatase-inducing activities of the polysaccharide, periodate oxidation-reduction and the controlled Smith degradation products were investigated, and the controlled Smith degradation product showed significant activity.

PMID: 1446371 [PubMed - indexed for MEDLINE]

169. Glycyrrhiza glabra extract as an effector of interception in Escherichia coli K12+.

Kuo S, Shankel DM, Telikepalli H, Mitscher LA.

Department of Microbiology, University of Kansas, Lawrence 66045.

Glycyrrhiza glabra polar lipid extract contains a number of flavonoids and related chemical compounds. Studies on the effectiveness of Glycyrrhiza glabra polar lipid extract in intercepting reactive molecules generated from the illumination of the photosensitizers rose bengal and phenosafranin indicate that it is effective in preventing cytotoxicity against E. coli K12+ in a dose-related fashion using illuminated rose bengal. Since only a modest scavenging of singlet oxygen generated from phenosafranin is observed, the effects of the extracts are less related to singlet oxygen-mediated oxidation of substrate (type II reactions) than non-singlet oxygen-mediated oxidation of substrate (type I reactions). Elevated levels of glutathione observed in exponentially growing cells of E. coli K12 were also observed.

PMID: 1377357 [PubMed - indexed for MEDLINE]

170. A strategy for discovering biologically active compounds with high probability in traditional Chinese herb remedies: an application of saiboku-to in bronchial asthma.

Homma M, Oka K, Yamada T, Niitsuma T, Ihto H, Takahashi N.

Division of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.

A novel strategy for discovering biologically active components in traditional Chinese herb remedies was performed from a pharmacokinetic view. The hypothesis was that the active compounds should appear in blood and urine with appropriate blood concentrations and urinary excretion rates after the administration of herbal-extract mixtures. In this research, we applied our procedures to Saiboku-To, one of the most popular Chinese herbal medicines in Japan. Consisting of 10 different plant extracts, it is used for the treatment of bronchial asthma. The analytical method adopted was a rapid-flow fractionation (RFF) for extraction-fractionation of lipophilic components in urine followed by silica-gel high-performance liquid chromatography (HPLC) equipped with a multichannel ultraviolet (uv) absorption detector. beta-D-Glucuronidase-treated urine samples collected before and after the administration of Saiboku-To to healthy and asthmatic subjects were treated with the RFF apparatus to afford three pH-dependent fractions: strongly acidic (S), weakly acidic (W), and neutral (N). HPLC of these fractions, monitored by the multichannel uv detector, showed three new peaks in the postadministrative urine: one in the N fraction, two in the W fraction, and none in the S fraction. A compound in the N fraction was identified with authentic magnolol, a major component in Magnolia officinalis. Two compounds in the W fraction were identified by comparison with authentic samples as 8,9-dihydroxydihydromagnolol and liquiritigenin, metabolites previously isolated from M. officinalis and Glycyrrhiza glabra, respectively.

Publication Types: PMID: 1352438 [PubMed - indexed for MEDLINE]

171. Characterization of a polysaccharide having activity on the reticuloendothelial system from the stolon of Glycyrrhiza glabra var. glandulifera.

Shimizu N, Tomoda M, Satoh M, Gonda R, Ohara N.

Kyoritsu College of Pharmacy, Tokyo, Japan.

An acidic polysaccharide, named glycyrrhizan GA, was isolated from the stolon of Glycyrrhiza glabra L. var. glandulifera Reg. et Herd. It produced a single band on electrophoresis and a single peak on gel chromatography, and its molecular mass was estimated to be 85,000. Glycyrrhizan GA is composed of L-arabinose: D-galactose: L-rhamnose: D-galacturonic acid: D-glucuronic acid in the molar ratio of 22:10:1:2:1, in addition to small amounts of O-acetyl groups. Part of the hexuronic acid residues exist as methyl esters. Methylation analysis, carbon-13 nuclear magnetic resonance and periodate oxidation studies indicated that its structural features include mainly alpha-arabino-beta-3,6-galactan type structural units. Glycyrrhizan GA showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test.

Publication Types: PMID: 1797429 [PubMed - indexed for MEDLINE]

173. Inhibition of adrenaline-induced aggregation of human platelets by Pakistani medicinal plants.

Sajid TM, Rashid S, Saeed SA.

Department of Pharmacology, Faculty of Pharmacy, University of Karachi, Karachi-75270, Pakistan.

The effects of extracts of Pakistani plants claiming medicinal value were observed on adrenaline-induced aggregation of human platelets according to the method of Born (1962). The extracts manifested significant inhibitory activity in doses of 0.625 mgm(-1) to 2.5 mgml(-1) in this in vitro model. The potency of the plant extracts in inhibiting platelet aggregation induced by adrenaline is in the following order: Sida pakistanica, IC50 = 0.90 mgml(-1) > Tribulus terrestris, IC50 = 0.97 mgml(-1) > Solanum surattense, IC50 = 1.34 mgml(-1) Tephrosia subtriflora, IC50 = 1.40 mgml(-1) > Glycyrrhiza glabra (butanolic extract), IC50 = 1.66 mgml(-1) > Urtica dioica IC50 = 2.17 mgml(-1). Further studies are proposed to find out whether the inhibition of adrenaline-induced platelet aggregation is mediated through alpha-adrenoceptor blockade or suppressed synthesis of prostaglandin endoperoxides.

PMID: 16414694 [PubMed]

174. [Phenolic constituents of licorice. IV. Correlation of phenolic constituents and licorice specimens from various sources, and inhibitory effects of licorice extracts on xanthine oxidase and monoamine oxidase]

[Article in Japanese]

Hatano T, Fukuda T, Liu YZ, Noro T, Okuda T.

Faculty of Pharmaceutical Sciences, Okayama University, Japan.

The roots and/or rhizomes of Glychyrrhiza uralensis, G. glabra and G. inflata, and commercial licorice specimens from various regions or countries were analyzed by high-performance liquid chromatography (HPLC), and classified into three types based on their phenolic constituents. i) Type A: The roots and rhizomes of G. uralensis, commercial licorice specimens from northwestern region of China (Seihoku-kanzo) and from northeastern region of China (Tohoku-kanzo) in Japanese markets, and also several licorice specimens from Chinese markets. They contain licopyranocoumarin (6), glycycoumarin (7) and/or licocoumarone (8), which were not found in G. glabra and G. inflata. ii) Type B: The root and rhizome of G. glabra, and the licorice specimens imported from the Soviet Union and Afghanistan. They contain glabridin (9) and glabrene (10), which were not found in the samples of the other two Glycyrrhiza species. A root sample of Glycyrrhiza species from Turkey also contains 9 and 10. iii) Type C: The root sample of G. inflata. They contain licochalcones A (11) and B (12), which were not found in the samples of the other two Glycyrrhiza species. Commercial licorice specimens obtained in Japan, which were imported from Sinkiang of China (Shinkyo-kanzo), and some licorice specimens obtained from Chinese markets, have also been found to contain 11 and 12. The phenolics 6-12, characteristic constituents of types A, B or C, were not found in a specimen of cortex-free licorice from a Japanese market (kawasari-kanzo). Extracts of some licorice specimens of types A and B, and all of the licorice specimens of type C inhibited 40-56% of the xanthine oxidase activity at the concentration of 30 micrograms/ml. Extracts of some licorice specimens of types A and B also showed inhibitory effects on monoamine oxidase (44-64% inhibition, at the concentration of 30 micrograms/ml), which were slightly weaker than that of harmane hydrochloride.

Publication Types:

PMID: 1941536 [PubMed - indexed for MEDLINE]

175. Inhibition of mouse skin tumor-initiating activity of DMBA by chronic oral feeding of glycyrrhizin in drinking water.

Agarwal R, Wang ZY, Mukhtar H.

Department of Dermatology, University Hospitals of Cleveland, OH.

Licorice (Glycyrrhiza glabra), a Mediterranean plant, has been used as an antidote, demulcent, and elixir folk medicine for generations in China. The main water-soluble constituent of licorice is glycyrrhizin (GL), which has been shown to possess several pharmacological properties. In this study, we show that oral feeding of GL to Sencar mice resulted in substantial protection against skin tumorigenesis caused by 7,12-dimethyl-benz [a]anthracene (DMBA) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. The latent period prior to the onset of tumor development was considerably prolonged in GL-fed animals compared with animals not fed GL and resulted in significant decrease in the number of tumors per mouse, during and at the termination of the experiment. Oral feeding of GL in drinking water also resulted in inhibition in the binding of topically applied [3H]benzo[a]pyrene and [3H]DMBA to epidermal DNA. The possible mechanism(s) of the antitumor-initiating activity may be due to the involvement of GL as inhibitor of the carcinogen metabolism followed by DNA adduct formation. Our results suggest that GL possesses considerable antitumorigenic activity and could prove useful in protecting some forms of human cancer.

Publication Types: PMID: 1907733 [PubMed - indexed for MEDLINE]

176. Metabolic effects of licorice roots (Glycyrrhiza glabra) on lipid distribution pattern, liver and renal functions of albino rats. MS.

Sitohy MZ, el-Massry RA, el-Saadany SS, Labib SM.

Biochemistry Department, Faculty of Agriculture, Zagazig University, Egypt.

The biochemical activity of licorice roots was investigated by administrating it to hypercholesterolaemic rats at two different doses. High cholesterol level in the serum and most organs of hypercholesterolaemic rats was accompanied by high levels of triglycerides and total lipids but low one of phospholipids. The hypocholesterolaemic action of licorice roots was accompanied by hypolipaemic action but higher level of phospholipids in the rat serum and most organs. The results showed that while the high cholesterol level in the rat serum has impairing effects on liver and renal functions, the licorice administered to these rats has a counteracting action i.e. it can improve the impaired function of both liver and p4f1ey, It has also a hypoglycaemic action.

PMID: 1780004 [PubMed - indexed for MEDLINE]

177. A further contribution to the triterpenoid constituents of Glycyrrhiza glabra L.

Elgamal MH, Hady FK, Hanna AG, Mahran GH, Duddeck H.

National Research Centre, Laboratory of Natural Products, Dokki-Cairo, Egypt.

Five pentacyclic triterpenoids have been isolated from the minor constituents of local liquorice roots, one of them has not been isolated before from liquorice root. Their structural formulae and stereochemical configuration was determined by spectroscopic methods. 13C and 1H NMR data have been compiled.

Publication Types: PMID: 2291771 [PubMed - indexed for MEDLINE]

178. Specificity of antimutagens against chemical mutagens in microbial systems.

Shankel DM, Clarke CH.

University of Kansas, Lawrence.

Procedures have been developed which enable the study of antimutagenic specificity of certain antimutagenic chemicals against chemical mutagens/carcinogens. Modifications of the Ames Salmonella assay, the Bacillis subtilis rec assay of Kada and co-workers, and the Luria-Delbrück fluctuation test, along with procedures we have developed utilizing E. coli K12 strain ND160 developed by Dworkin, all are employed in these studies. Using these procedures, a number of naturally-occurring compounds and/or their derivatives have been shown to produce antimutagenic specificity either against changes at different specific genetic loci or against activity of specific chemical mutagens such as nitrofurazone, ethyl methanesulfonate, or caffeine. Compounds that demonstrate this activity include cinnamaldehyde, chlorophyllin, an extract of Glycyrrhiza glabra, spermine, and mixtures of guanosine and cytidine. The data demonstrate that some antimutagens act specifically against spontaneous mutations, while others inhibit the development of chemically-induced mutations at specific loci. These results have potential application to the prevention of chemical toxicological damage.

Publication Types:

PMID: 2327947 [PubMed - indexed for MEDLINE]

179. Biotransformation of 18 beta-glycyrrhetinic acid by cell suspension cultures of Glycyrrhiza glabra.

Hayashi H, Fukui H, Tabata M.

Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

Two biotransformation products formed from 18 beta-glycyrrhetinic acid by cell suspension cultures of Glycyrrhiza glabra were isolated and their structures determined by chemical and spectral data as 3-O-[alhpa-L-arabinopyranosyl-(1----2)-beta-D-Glucuronopy ranosyl]-24- hydroxy-18 beta-glycyrrhetinic acid and 30-O-beta-D-glycopyrano-syl-18 beta-glycyrrhetinic acid. The formation of glycyrrhizin, the main triterpene glucuronide of the licorice root, was not detected among the biotransformation products. This is the first report of the glucuronylation of an exogenous triterpene in plant cell cultures.

PMID: 1366692 [PubMed - indexed for MEDLINE]

180. Effect of ayurvedic medicines on beta-glucuronidase activity of Brunner's glands during recovery from cysteamine induced duodenal ulcers in rats.

Nadar TS, Pillai MM.

Biochemical and histochemical studies revealed decreased beta-glucuronidase activity in the Brunner's glands of duodenal ulcerated rats. The enzyme activity showed gradual increase during recovery. Rats treated with a mixture of Ayurvedic medicines (Glycyrrhiza glabra, Terminalia chebula, Piper longum and Shanka Bhasma) recovered faster with concomitant increase in beta-glucuronidase activity in the Brunner's glands. It can be concluded that Ayurvedic medicines used do not act as antacid but improve the secretory status of Brunner's glands involved in the protection against duodenal ulcer.

Publication Types: PMID: 2620935 [PubMed - indexed for MEDLINE]

182. [Pharmacological study of the anti-inflammatory agent glyderinine]

[Article in Russian]

Azimov MM, Zakirov UB, Radzhapova ShD.

In experiments on various animals glyderinine, a derivative of glycyrrhizic acid isolated from Glycyrrhiza glabra, was found to exert a pronounced anti-inflammatory effect exceeding that of hydrocortisone and amidopyrine. The mechanism of the anti-inflammatory effect was to a certain degree related to the adrenal cortex, suppression of vascular permeability and antagonism to inflammation as well. Similarly to other anti-inflammatory agents, glyderinine possesses analgesic and antipyretic properties, but unlike them it fails to suppress hemopoiesis and to cause ulceration of the gastrointestinal mucosa. The drug is of low toxicity and exerts the antiallergic effect. Glyderinine was successfully tried and recommended for a wide use as an ointment for treating skin diseases.

Publication Types: PMID: 3191985 [PubMed - indexed for MEDLINE]

183. Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus.

Shinada M, Azuma M, Kawai H, Sazaki K, Yoshida I, Yoshida T, Suzutani T, Sakuma T.

The effects of glycyrrhizin, a component of licorice (Glycyrrhiza glabra) roots, on the production of interferon-gamma in human peripheral lymphocyte-macrophage cultures by concanavalin A (Con A) was examined. Interferon-gamma production in normal lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of glycyrrhizin at 37 degrees C for 12 hr or longer, and then treated with 10 micrograms/ml of Con A, was enhanced four to eight times compared to control cell cultures. Lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of glycyrrhizin alone did not produce interferon. No significant difference in the adsorption of [3H]Con A to glycyrrhizin-treated and control lymphocyte-macrophage cultures was found, but RNA and protein synthesis of the treated lymphocytes was increased compared to control cells; DNA synthesis, however, was reduced. Collaboration between enriched T-lymphocytes and macrophages, both treated with glycyrrhizin, was needed for the enhancement of interferon-gamma production. A smaller increase in interferon production was also observed in the glycyrrhizin-treated peripheral lymphocyte-macrophage cultures derived from an asymptomatic carrier of hepatitis B virus, in response to Con A and surface antigen of hepatitis B virus.

PMID: 3080754 [PubMed - indexed for MEDLINE]
184. Screening of the wormicidal Chinese raw drugs on Clonorchis sinensis.

Rhee JK, Woo KJ, Baek BK, Ahn BJ.

The wormicidal effect on Clonorchis sinensis in boiled water extracts of 223 species (vegetable origin 206, animal origin 10, mineral origin 7) of raw drugs prescribed in Oriental medicine was observed in vitro. The wormicidal substances were detected from 31 of the above-mentioned species. The wormicidal substances extracted from Platycodon grandiflorum (radix), Schizandra chinensis (fruit), Polygala tenuifolia (herb) and Aster tataricus (radix) were most effective. Those from Smilax glabra (radix), Pueraria thunbergiana (flower, radix), Polygala tenuifolia (radix), Scutellaria baicalensis (radix), Prunus mume (fruit), Glycyrrhiza uralensis (radix), Angelica koreana (radix), Phytolacca esculenta (radix) and Cyrtomium fortunei (rhizoma) were effective. The rest of the raw drugs were less effective.

PMID: 6764091 [PubMed - indexed for MEDLINE]

185. Traditional medicine in health care.

Sayed MD.

The state of research on plants used in traditional medicine and its development in Egypt is indicated by the number of scientific institutions devoted to this problem: Universities, the National Research Centre, the Desert Institute and the Horticulture Department of the Ministry of Agriculture. Moreover, the use of certain medicinal plants has been "industrialised', e.g., Ammi visnaga, Cymbopogon proximus, Nigella sativa and Aloe vera. Other plants are under investigation: Urginea maritima, Phytolacca americana and Euphorbia sp. (known for its claimed antitumour properties), Glycyrrhiza glabra, Cynara scolymus and Solanum laciniatum.

PMID: 7464176 [PubMed - indexed for MEDLINE]

186. Antimicrobial agents from higher plants. Antimicrobial isoflavanoids and related substances from Glycyrrhiza glabra L. var. typica.

Mitscher LA, Park YH, Clark D, Beal JL.

Bioassay-directed fractionation of Glycyrrhiza glabra L. var. typica resulted in the isolation and characterization of glabridin (I), glabrol (2), glabrene (3), 3-hydroxyglabrol (4), 4'-O-methylglabridin (5), 3'-methoxyglabridin (6), formononetin (7), phaseollinisoflavan (8), hispaglabridin A (9), hispaglabridin B (13), salicylic acid and O-acetyl salicylic acid. Of these, hispaglabridin A, hispaglabridin B, 4'-O-methylglabridin, glabridin, glabrol and 3-hydroxyglabrol possess significant antimicrobial activity in vitro; hispaglabridin A, hispaglabridin B, 3'-methoxyglabridin, 4'-O-methylglabridin 3-hydroxyglabrol, phaseollinisoflavan, salicylic acid, and O, acetyl salicylic acid are newly found in Glycyrrhiza sp.; and hispaglabridin A, hispaglabridin B, 3'-methoxyglabridin, 4'-O-methylglabridin, and 3-hydroxyglabrol are new to the literature and their structures are proposed herein.

Publication Types:

PMID: 7381508 [PubMed - indexed for MEDLINE]

192. Glycyrrhizic acid inhibits virus growth and inactivates virus particles.

Pompei R, Flore O, Marccialis MA, Pani A, Loddo B.

Screening investigations in antiviral action of plant extracts have revealed that a component of Glycyrrhiza glabra roots, found to be glycyrrhizie acid, is active against viruses. We report here that this drug inhibits growth and cytopathology of several unrelated DNA and RNA viruses, while not affecting cell activity and ability to replicate. In addition, glycyrrhizic acid inactivates herpes simplex virus particles irreversibly.

PMID: 233133 [PubMed - indexed for MEDLINE]

193. [High-performance liquid-liquid chromatography in beverage analysis]

[Article in French]

Bricout J, Koziet Y, de Carpentrie B.

Liquid liquid chromatography was performed with columns packed with stationary phases chemically bonded to silica microparticules. These columns show a high efficiency and are used very easily. Flavouring compounds like aromatic aldehydes which have a low volatility were analyzed in brandy using a polar phase alkylnitrile. Sapid substances like amarogentin in Gentiana lutea or glyryrrhizin in Glycyrrhiza glabra were determined by reversed phase chromatography. Finally ionizable substances like synthetic dyes can be analyzed by paired ion chromatography witha non polar stationary phase.

Publication Types: PMID: 754597 [PubMed - indexed for MEDLINE]


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