title: Yokukansan, a kampo medicine, protects PC12 cells from glutamate-induced death by augmenting gene expression of cystine/glutamate antiporter system Xc-.
abstract: Effects of the kampo medicine yokukansan on gene expression of the cystine/glutamate antiporter system Xc-, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc- subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook.
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Inashiki, Ibaraki, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kanno
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Inashiki, Ibaraki, Japan.
authors.forename: Zenji
authors.initials: Z
authors.lastname: Kawakami
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Inashiki, Ibaraki, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Mizoguchi
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Inashiki, Ibaraki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Inashiki, Ibaraki, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology; D020835:Medicine, Kampo; D016716:PC12 Cells / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D027182:Amino Acid Transport System y+
chemical_list: D000470:Alkaloids; D026922:Amino Acid Transport Systems, Acidic; D004365:Drugs, Chinese Herbal; D027282:Fusion Regulatory Protein 1, Heavy Chain; D005971:Glutamates; D005978:Glutathione; D026121:Indole Alkaloids; D020011:Protective Agents; C524644:Yi-Gan San; C110832:geissoschizine methylether; C063774:hirsuteine; C038369:hirsutine; C000723960:Slc7a11 protein, rat; D027182:Amino Acid Transport System y+