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.
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