title: Glycyrrhizin and its metabolite 18 beta-glycyrrhetinic acid in glycyrrhiza, a constituent herb of yokukansan, ameliorate thiamine deficiency-induced dysfunction of glutamate transport in cultured rat cortical astrocytes.
abstract: Effects of yokukansan, a traditional Japanese medicine, on thiamine deficiency (TD)-induced decrease of glutamate uptake were examined in cultured rat cortical astrocytes. Yokukansan (100-500 microg/ml) ameliorated the TD-induced decrease in glutamate uptake by astrocytes, implying that yokukansan may contain active herbs and compounds possessing this effect. Among the seven constituent herbs of yokukansan, significant effects were found for glycyrrhiza. Furthermore, glycyrrhizin and its metabolite 18 beta-glycyrrhetinic acid (10(-7)-10(-4)M), among the eight components of glycyrrhiza, ameliorated the TD-induced decrease of glutamate uptake in astrocytes in a concentration-dependent manner. These substances inhibited protein kinase C (PKC) activity under the in vitro conditions. These lines of evidence suggest that glycyrrhizin, a main component of glycyrrhiza, and its metabolite 18 beta-glycyrrhetinic acid are likely responsible for amelioration of dysfunction of glutamate transport in astrocytes. The inhibition of the PKC activity might be related to the pharmacological efficacy of these substances.
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. kawakami_zenji@mail.tsumura.co.jp
authors.forename: Zenji
authors.initials: Z
authors.lastname: Kawakami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D018698:Glutamic Acid / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000378:metabolism / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D013832:Thiamine Deficiency / Q000378:metabolism* / Q000473:pathology
chemical_list: D004365:Drugs, Chinese Herbal; D047428:Protein Kinase Inhibitors; C524644:Yi-Gan San; C119129:18alpha-glycyrrhetinic acid; D018698:Glutamic Acid; D019695:Glycyrrhizic Acid; D011494:Protein Kinases; D006034:Glycyrrhetinic Acid