Research Paper Volume 11, Issue 12 pp 4032—4049
Long-time qingyan formula extract treatment exerts estrogenic activities on reproductive tissues without side effects in ovariectomized rats and via active ER to ERE-independent gene regulation
- 1 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
- 2 Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
received: February 21, 2019 ; accepted: June 13, 2019 ; published: June 19, 2019 ;https://doi.org/10.18632/aging.102035
How to Cite
Copyright: Zheng 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.
The reproductive tissues are negatively influenced by estrogens in hormone therapy. Qingyan formula ethanol extract (QYFE)’s estrogenic effects and safety on reproductive tissues after long-term administration and its mechanism via estrogen receptor (ER) pathway haven’t been studied. Here, we characterized its estrogenic effects using ovariectomized rats together with in vitro studies for further molecular characterization. Ovariectomized rats were treated with QYFE at doses of 0.7, 1.4, and 2.8g/kg for 12 weeks. The results showed QYFE has a potent estrogenic activity, as indicated by restoring the disappeared estrous cycle, antagonizing the atrophy of uterus, vagina and mammary gland, and the estrogen decline in circulation caused by ovariectomy. In addition, QYFE upregulated ERα and ERβ expressions and had a less stimulatory effect on PCNA and ki-67 antigen in reproductive tissues compared with estradiol valerate. QYFE components can bind to ERα and ERβ, significantly increased ERα/β-ERE luciferase reporter gene expression, upregulated the expressions of ERs, PR and pS2 in MCF-7 cells at protein and gene level. All these activities were significantly inhibited by the ER antagonist ICI182,780. QYFE’s estrogenic activity maybe mediated by stimulating biosynthesis of estrogen and increasing the quantity of ERs in target tissue and via active ER to ERE-independent gene regulation.