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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

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Abstract

Rationale

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.

Objectives

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.

Methods

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 Rb1, ritanserin was given as pretreatment 15 min before the daily administration of ginsenoside Rb1 and the antagonistic effect was compared with ginsenoside Rb1 alone.

Results

Ginsenoside Rb1 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 Rb1.

Conclusions

We suggest that ginsenoside Rb1 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 Rb1.

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Acknowledgments

This research was supported, in part, by a research grant from the Medical Society for Ginseng Research. We are indebted to Drs. Masazumi Miyakoshi and Toshiyuki Murakami, Natural Products Research Department, Maruzen Pharmaceuticals (Hiroshima, Japan), for donating the ginsenoside Rb1 metabolites following the determination of purity. Dr. Keiichi Samukawa, an academic advisor to Ohki Pharmaceuticals (Tokyo, Japan), generously supplied ginsenosides of high purity.

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Authors and Affiliations

  1. Department of Pharmacology and Pharmacy, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan

    Noriko Yamada & Hiroaki Araki

  2. Behavioral Pharmacology Laboratory, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan

    Hiroyuki Yoshimura

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  1. Noriko Yamada
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  2. Hiroaki Araki
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Correspondence to Hiroyuki Yoshimura.

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Yamada, N., Araki, H. & Yoshimura, H. 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. Psychopharmacology 216, 589–599 (2011). https://doi.org/10.1007/s00213-011-2252-1

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