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

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 ERß 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 ERß, and significantly induce ERα/ß-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.

Effect of the Interaction of Veratrum Nigrum with Panax Ginseng on Estrogenic Activity In Vivo and In Vitro.

Panax ginseng (GS) and Veratrum nigrum (VN) are representative of incompatible pairs in "eighteen antagonistic medicaments" that have been recorded in the Chinese medicinal literature for over 2,000 years. However, evidence linking interference effects with combination use is scare. Based on the estrogen-like effect of GS described in our previous studies, we undertake a characterization of the interaction on estrogenic activity of GS and VN using in vivo models of immature and ovariectomized (OVX) mice and in vitro studies with MCF-7 cells for further mechanism. VN decreased the estrogenic efficacy of GS on promoting the development of the uterus and vagina in immature mice, and reversing the atrophy of reproductive tissues in OVX mice. VN interfered with the estrogenic efficacy of GS by decreasing the increase of the serum estradiol and the up-regulation of ERα and ERß expressions by treatment with GS. And VN antagonized the estrogenic efficacy of GS on promoting the viability of MCF-7 cells and up-regulation of protein and gene expressions of ERs. In conclusion, this study provided evidence that GS and VN decreased effects on estrogenic activity, which might be related to regulation of estrogen secretion and ERs.

Short-time QiBaoMeiRan Formula Treatment Exerts Estrogenic Activities without Side Effects on Reproductive Tissues in Immature Mice.

The Chinese herbal preparation QiBaoMeiRan formula (QBMR) displayed estrogenic effects in ovariectomized rats after long-term administration in a previous study. The uterus and vagina are negatively influenced by estrogens in hormone therapy. While QBMR is known to be a phytoestrogen, its estrogenic effects and safety on reproductive tissues after short-term administration and its mechanism via estrogen receptor (ER) pathway haven't been studied. Here, we characterized its estrogenic effects using immature mice together with in vitro studies for further molecular characterization. Immature mice were treated with QBMR at doses of 1.125, 2.25, and 4.5 g/kg for 7 days. 1.125 and 2.25 g/kg QBMR promoted the growth and development of uterus and vagina, and upregulated ERα and ERß expression in reproductive tissues. QBMR had a stimulatory effect on proliferating cell nuclear antigen in vagina but not in uterus, and was without any influence on ki-67 antigen in uterus and vagina. QBMR significantly induced luciferase expression from the ERα/ß-estrogen response element (ERE) luciferase reporter and upregulated ERα and ERß expressions in MCF-7 cells, which were significantly inhibited by estrogen antagonist ICI182,780. This study demonstrated QBMR exerts estrogenic effects on reproductive tissues without side effects and through ER-ERE-dependent pathway.

Estrogenic effect of the extract of Renshen (Radix Ginseng) on reproductive tissues in immature mice.

OBJECTIVE: To evaluate the estrogenic efficacy of Renshen (Radix Ginseng) (GS) on reproductive target tissues in immature mice. METHODS: One hundred and ten female immature Kunming (KM) mice, 21-day-old, were randomly assigned to eleven groups, 10 for each; one served as control group treated with 0.154 mg/kg estradiol valerate (EV, n = 10), the rest were treated respectively with GS intragastrically at a daily dose of 0.5, 1.0, 1.5, 3.0, 6.0, 12.0, 18.0, 24.0 and 30.0 g/kg (n = 10 in per group) for 7 days. The estrous cycle, uterine weight, hormone levels in circulation and histomorphology changes of uterus and vagina were scrupulously examined. The estrogen receptor (ER) α and ERß expressions in the uterus and vagina were detected by immunohistochemistry and western blotting. RESULTS: Treatment with GS at the dose of 12.0, 18.0 and 24.0 g/kg resulted significant estrogenic activity in the mice, as indicated by advanced and prolonged estrous stage and increased uterine weight (all P < 0.05). GS treatment substantially promoted development of reproductive tisue by thickening the uterine endometrium and increasing vaginal epithelial layers. In addition, treatment with GS induced significant up-regulation of ERα and ERß expressions in reproductive tissues, and ERα up-regulation was stronger than that of ERß. GS could raise levels of circulating estrogen, simultaneously decrease levels of luteinizing hormone and follicle-stimulating hormone (all P < 0.001) compared with the control group. CONCLUSION: Our findings suggest that GS had estrogenic effect on reproductive tissues in immature mice by stimulating biosynthesis of estrogen in circulation and up-regulating ERs.