Identification of Steroidogenic Components Derived From Gardenia jasminoides Ellis Potentially Useful for Treating Postmenopausal Syndrome.

Xueyu Wang,Tzi Bun Ng,Guo-Cai Wang,Yan Bo Zhang,Ken Kin Lam Yung,Jianhui Rong,Shi Wei Wang,Kai Fai Lee,Stephen Cho Wing Sze,Hei-Kiu Wong,Lin Zheng

doi:10.3389/fphar.2018.00390

Abstract

Estrogen-stimulating principles have been demonstrated to relieve postmenopausal syndrome effectively. Gardenia jasminoides Ellis (GJE) is an herbal medicine possessing multiple pharmacological effects on human health with low toxicity. However, the therapeutic effects of GJE on the management of postmenopausal syndrome and its mechanism of action have not been fully elucidated. In this study, network pharmacology-based approaches were employed to examine steroidogenesis under the influence of GJE. In addition, the possibility of toxicity of GJE was ruled out and four probable active compounds were predicted. In parallel, a chromatographic fraction of GJE with estrogen-stimulating effect was identified and nine major compounds were isolated from this active fraction. Among the nine compounds, four of them were identified by network pharmacology, validating the use of network pharmacology to predict active compounds. Then the phenotypic approaches were utilized to verify that rutin, chlorogenic acid (CGA) and geniposidic acid (GA) exerted an estrogen-stimulating effect on ovarian granulosa cells. Furthermore, the results of target-based approaches indicated that rutin, CGA, and GA could up-regulate the FSHR-aromatase pathway in ovarian granulosa cells. The stimulation of estrogen production by rat ovarian granulosa cells under the influence of the three compounds underwent a decline when the follicle-stimulating hormone receptor (FSHR) was blocked by antibodies against the receptor, indicating the involvement of FSHR in the estradiol-stimulating activity of the three compounds. The effects of the three compounds on estrogen biosynthesis- related gene expression level were further confirmed by Western blot assay. Importantly, the MTT results showed that exposure of breast cancer cells to the three compounds resulted in reduction of cell viability, demonstrating the cytotoxicity of the three compounds. Collectively, rutin, chlorogenic acid and geniposidic acid may contribute to the therapeutic potential of GJE for the treatment of postmenopausal syndrome.

Highlights

Natural menopause is classified as permanent cessation of menstruation, induced by ovarian follicular failure and ovarian hormone instability (Burger et al, 2007)
There were 196 phytochemicals reported in Gardenia jasminoides Ellis (GJE) by TCMSP database, 49 phytochemicals reported in GJE by Traditional Chinese Medicine (TCM) database @ Taiwan and 166 phytochemicals reported in GJE by TCMID database
There were 4 targets in menopause reported by TTD database, 37 targets in menopause reported by DrugBank database, and 932 genes in menopause reported by GeneCards database

Summary

Introduction

Natural menopause is classified as permanent cessation of menstruation, induced by ovarian follicular failure and ovarian hormone instability (Burger et al, 2007). More than 50% of women in the world are afflicted with postmenopausal syndrome at the climacteric stage (Su et al, 2013; Dalal and Agarwal, 2015). It is widely accepted that estrogen deprivation plays an important role in the postmenopausal syndrome (World Health Organization, 1996; Greendale et al, 1998; Constantine and Pickar, 2003). To relieve the reduced level of estrogen, women in climacterium usually opt to undergo hormone replacement therapy (HRT) (Barnabei et al, 2002). A safe and effective treatment of postmenopausal syndrome is necessitated

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