Research Paper|Volume 9, Issue 1|pp 156—172

Salvia miltiorrhiza bunge increases estrogen level without side effects on reproductive tissues in immature/ovariectomized mice

Ying Xu¹, Ting Chen¹, Xin Li¹, Ya-kun Qu¹, Jin-na An¹, Hong-xia Zheng¹, Zi-jia Zhang², Na Lin¹

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
²Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 100101, China

* * Equal contribution

Received: October 28, 2016Accepted: December 12, 2016Published: December 20, 2016

Copyright: © 2016 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Salvia miltiorrhiza bunge(SM) is a popular herb for alleviating menopausal symptoms, although the scientific evidence of applying SM to estrogen replacement therapy is limited. In this study, we characterized the estrogenic activity of SM using in vivo models of immature and ovariectomized (OVX) mice and performed in vitro studies focusing on the estrogen receptor (ER) pathway for further molecular characterizations. SM treatments demonstrated significant estrogenic activity by promoting the development of uterus and vagina in immature mice, restoring the estrus cycle and reversing the atrophy of reproductive tissues in OVX mice, as well as increasing the expressions of ERα and ERβ at protein and mRNA level in the reproductive tissues. Meanwhile, SM significantly increased estradiol in serum, and decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the circulation of immature and OVX mice. SM could stimulate the binding effect of ERα and ERβ, and significantly induce ERα/β-estrogen response element (ERE) luciferase reporter gene expression. All these activities were inhibited by the ER antagonist ICI182, 780. This study demonstrates SM exerts estrogenic effects by stimulating biosynthesis of estrogen and increasing ERs in target tissues without side effects on reproductive tissues and through ER-ERE-dependent pathway.