title: Influences of yokukansankachimpihange on aggressive behavior of zinc-deficient mice and actions of the ingredients on excessive neural exocytosis in the hippocampus of zinc-deficient rats.
abstract: We examined the effect of Yokukansankachimpihange (YKSCH), a form of Yokukansan containing parts of two herbaceous plants, Citrus Unshiu Peel (Chimpi) and Pinellia Tuber (Hange), on aggressive behavior of mice housed individually. Mice were fed a zinc-deficient diet for 2 weeks. In a resident-intruder test, the cumulative duration of aggressive behavior was decreased in zinc-deficient mice administrated drinking water containing YKSCH (approximately 300 mg/kg body weight/day) for 2 weeks. We tested mice for geissoschizine methyl ether (GM), which is contained in Uncaria Hook, and 18β-glycyrrhetinic acid (GA), a major metabolite of glycyrrhizin contained in Glycyrrhiza, which were contained in YKS and YKSCH. In hippocampal slices from zinc-deficient rats, excess exocytosis at mossy fiber boutons induced with 60 mM KCl was attenuated in the presence of GA (100-500 µM) or GM (100 µM). The intracellular Ca2+level, which showed an increase induced by 60 mM KCl, was also attenuated in the presence of GA (100-500 µM) or GM (100 µM). These results suggest that GA and GM ameliorate excess glutamate release from mossy fiber boutons by suppressing the increase in intracellular Ca2+signaling. These ameliorative actions may contribute to decreasing the aggressiveness of mice individually housed under zinc deficiency, potentially by suppressing excess glutamatergic neuron activity in the hippocampus.
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52- 1 Yada, Shizuoka 422-8526, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Tamano
authors.forename: Enya
authors.initials: E
authors.lastname: Yusuke
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ide
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
mesh_terms: D000374:Aggression / Q000187:drug effects*; D000818:Animals; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects*; D026121:Indole Alkaloids / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000172:deficiency*
chemical_list: D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; C110832:geissoschizine methylether; C000607904:yokukansankachimpihange; C119129:18alpha-glycyrrhetinic acid; D015032:Zinc; D006034:Glycyrrhetinic Acid