title: Salvia miltiorrhiza bunge increases estrogen level without side effects on reproductive tissues in immature/ovariectomized mice.
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 usingin vivomodels of immature and ovariectomized (OVX) mice and performedin vitrostudies 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.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Ya-Kun
authors.initials: YK
authors.lastname: Qu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Jin-Na
authors.initials: JN
authors.lastname: An
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Zheng
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 100101, China.
authors.forename: Zi-Jia
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lin
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D030762:Estrous Cycle / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D051379:Mice; D010052:Ovariectomy; D010936:Plant Extracts / Q000494:pharmacology*; D027561:Salvia miltiorrhiza; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism
chemical_list: D065171:Estrogen Receptor Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010936:Plant Extracts; D000077267:Fulvestrant; D004958:Estradiol
keywords: Salvia miltiorrhiza bunge; estrogen receptor antagonist ICI182, 780; estrogen receptors; estrogenic effect; reproductive target tissue