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葛根素通过差异募集核受体共激活因子到雌激素受体-α来部分抑制子宫内膜间质细胞的增殖。

Puerarin suppresses proliferation of endometriotic stromal cells in part via differential recruitment of nuclear receptor coregulators to estrogen receptor-α.

机构信息

Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China; Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai, China.

出版信息

J Steroid Biochem Mol Biol. 2013 Nov;138:421-6. doi: 10.1016/j.jsbmb.2013.07.006. Epub 2013 Jul 29.

DOI:10.1016/j.jsbmb.2013.07.006
PMID:23907019
Abstract

BACKGROUND AND OBJECTIVES

Puerarin, a phytoestrogen with a weak estrogenic effect, binds to estrogen receptors, thereby competing with 17β-estradiol and producing an anti-estrogenic effect. In our early clinical practice to treat endometriosis, a better therapeutic effect was achieved if the formula of traditional Chinese medicine included Radix puerariae. This study was to investigate whether puerarin could suppress the proliferation of endometriotic stromal cells (ESCs) and to further elucidate the potential mechanism.

METHODS AND RESULTS

The ESCs were successfully established. The effects of puerarin on the proliferation of ESCs, cell cycle and apoptosis were determined by Cell Counting Kit-8 assay and flow cytometry. The mRNA and protein levels of cyclin D1 and cdc25A were detected by real-time PCR and Western blot analysis. Coimmunoprecipitation was applied to examine the recruitment of nuclear receptor coregulators to the estrogen receptor-α. We found that puerarin can suppress estrogen-stimulated proliferation partly through down-regulating the transcription of cyclin D1 and cdc25A by promoting the recruitment of corepressors to estrogen receptor-α as well as limiting that of coactivators in ESCs.

CONCLUSIONS

Our data suggest that puerarin could suppress the proliferation of ESCs and could be a potential therapeutic agent for the treatment of endometriosis.

摘要

背景与目的

葛根素是一种具有弱雌激素作用的植物雌激素,与雌激素受体结合,从而与 17β-雌二醇竞争,并产生抗雌激素作用。在我们早期治疗子宫内膜异位症的临床实践中,如果中药配方中包含葛根,会取得更好的治疗效果。本研究旨在探讨葛根素是否能抑制子宫内膜间质细胞(ESCs)的增殖,并进一步阐明其潜在机制。

方法与结果

成功建立了 ESCs。通过细胞计数试剂盒-8 检测和流式细胞术检测葛根素对 ESCs 增殖、细胞周期和凋亡的影响。实时 PCR 和 Western blot 分析检测细胞周期蛋白 D1 和 cdc25A 的 mRNA 和蛋白水平。免疫共沉淀检测核受体共激活因子向雌激素受体-α的募集。我们发现,葛根素可以通过促进核受体共激活因子向雌激素受体-α募集,限制共激活因子向雌激素受体-α募集,从而抑制雌激素刺激的增殖,部分下调 cyclin D1 和 cdc25A 的转录。

结论

我们的数据表明,葛根素可以抑制 ESCs 的增殖,可能成为治疗子宫内膜异位症的潜在治疗药物。

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Puerarin suppresses proliferation of endometriotic stromal cells in part via differential recruitment of nuclear receptor coregulators to estrogen receptor-α.葛根素通过差异募集核受体共激活因子到雌激素受体-α来部分抑制子宫内膜间质细胞的增殖。
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