Gomisin N, a major lignan in Schisandra chinensis, increases production of testosterone and 17β-estradiol via stimulating steroidogenic enzymes

Abstract

Schisandra chinensis, which is called Omija in Korean, has been widely used as herbal medicine for many symptoms including sexual enhancement in East Asia. There are many studies that have focused on the biological activities of lignans in Schisandra chinensis such as gomisin N, gomisin A, and schizandrin (schisandrol A). Estrogen is a primary sex hormone in females. Estrogen plays important roles in reproductive and non-reproductive organs. When estrogen level decreases as women experience menopause, the risk for cardiovascular disease, depression, osteoporosis etc. increases. Therefore, maintaining physiological estrogen levels is beneficial to women with low estrogen level. As society becomes more and more aged, an interest in menopause is increasing. Although the hormone replacement therapy (HRT) is representative treatment for relieving symptoms of menopause, a demand for natural compounds to be used on menopausal symptoms increases because of the side effects of long term HRT. For these reasons, the effect of Schisandra chinensis on relieving menopausal symptoms and ovarian failure has been already reported. However, the active compound and mechanisms need to be determined. We aimed to identify the active compound of Schisandra chinensis. In addition, we focused on the effects of its active compound on steroidogenesis. In this study, we used NCI-H295R cell line derived from human adrenal glands which is a model for studying steroidogenesis pathway. Among the three major lignans, we found that gomisin N promoted the production of testosterone and 17β-estradiol. To consider the effect on steroidogenesis and an abundance of composition in Schisandra chinensis, Gomisin N was chosen as an active compound. Gomisin N also has effects on steroidogenic enzymes. It increased the protein and gene expression levels of CYP11A1 and CYP17A1. Therefore, gomisin N may have promoted the production of testosterone and 17β-estradiol by increasing the amount of substrates such as pregnenolone and androstenedione. In addition, gomisin N tended to increase the concentration of testosterone and 17β-estradiol in mouse antral follicles and 40 μM of gomisin N was the most effective in inducing steroid synthesis.