Identification of antidepressant-like ingredients in ginseng root (Panax ginseng C.A. Meyer) using a menopausal depressive-like state in female mice: participation of 5-HT2A receptors

After reports of adverse effects with hormone replacement therapy, such as reproductive and breast cancer and coronary heart disease, much attention has been given to the development of new remedies to alleviate menopausal depression in women, but methods for their preclinical evaluation have not been clarified. We previously developed a procedure to predict the drug effect on the menopausal depressive-like state in female mice. We attempted to identify psychoactive components from ginseng root, one of the earliest known materials for menopausal disorder, and to clarify the possible mechanism involved. As an index of a depressive-like state, we used the prolongation of immobility time induced by an ovariectomy during the forced swimming test. Chronic treatment with the candidate substance began the day after ovariectomy and continued for 14 days. To examine whether the 5-HT2A receptor antagonist ritanserin antagonized the antidepressant-like effect of ginsenoside Rb-1, ritanserin was given as pretreatment 15 min before the daily administration of ginsenoside Rb-1 and the antagonistic effect was compared with ginsenoside Rb-1 alone. Ginsenoside Rb-1 and compound K were active ingredients that dose-dependently prevented the prolongation of immobility time induced by ovariectomy. Co-administration of ritanserin, a 5-HT2A-receptor antagonist, antagonized the effect of ginsenoside Rb-1. We suggest that ginsenoside Rb-1 and its metabolite, compound K, are antidepressant-like components of the ginseng root, and that 5-HT2A receptors may play an important role in mediating the antidepressant-like effect of ginsenoside Rb-1.