Puerarin Suppresses Proliferation of Endometriotic Stromal Cells Partly Via the MAPK Signaling Pathway Induced by 17ß-estradiol-BSA

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Oct 3

PMID 23029074

Citations 18

Authors

Wen Cheng

Lizao Chen

Shengsheng Yang

Jie Han

Dongxia Zhai

Jian Ni

Chaoqin Yu

Zailong Cai

Affiliations

Soon will be listed here.

Abstract

Background: Puerarin is a major isoflavonoid compound extracted from Radix puerariae. It has a weak estrogenic action by binding to estrogen receptors (ERs). In our early clinical practice to treat endometriosis, a better therapeutic effect was achieved if the formula of traditional Chinese medicine included Radix puerariae. The genomic and non-genomic effects of puerarin were studied in our Lab. This study aims to investigate the ability of puerarin to bind competitively to ERs in human endometriotic stromal cells (ESCs), determine whether and how puerarin may influence phosphorylation of the non-genomic signaling pathway induced by 17ß-estradiol conjugated to BSA (E(2)-BSA).

Methodology: ESCs were successfully established. Binding of puerarin to ERs was assessed by a radioactive competitive binding assay in ESCs. Activation of the signaling pathway was screened by human phospho-kinase array, and was further confirmed by western blot. Cell proliferation was analyzed according to the protocol of CCK-8. The mRNA and protein levels of cyclin D1, Cox-2 and Cyp19 were determined by real-time PCR and western blotting. Inhibitor of MEK1/2 or ER antagonist was used to confirm the involved signal pathway.

Principal Findings: Our data demonstrated that the total binding ability of puerarin to ERs on viable cells is around 1/3 that of 17ß-estradiol (E(2)). E(2)-BSA was able to trigger a rapid, non-genomic, membrane-mediated activation of ERK1/2 in ESCs and this phenomenon was associated with an increased proliferation of ESCs. Treating ESCs with puerarin abrogated the phosphorylation of ERK and significantly decreased cell proliferation, as well as related gene expression levels enhanced by E(2)-BSA.

Conclusions/significance: Puerarin suppresses proliferation of ESCs induced by E(2)-BSA partly via impeding a rapid, non-genomic, membrane-initiated ERK pathway, and down-regulation of Cyclin D1, Cox-2 and Cyp19 are involved in the process. Our data further show that puerarin may be a new candidate to treat endometriosis.

Citing Articles

Altered Differential Expression of Genes and microRNAs Related to Adhesion and Apoptosis Pathways in Patients with Different Phenotypes of Endometriosis.

Antonio L, Meola J, Rosa-E-Silva A, Nogueira A, Candido Dos Reis F, Poli-Neto O Int J Mol Sci. 2023; 24(5).

PMID: 36901866 PMC: 10002379. DOI: 10.3390/ijms24054434.

Endometriosis and Phytoestrogens: Friends or Foes? A Systematic Review.

Bartiromo L, Schimberni M, Villanacci R, Ottolina J, Dolci C, Salmeri N Nutrients. 2021; 13(8).

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Phytoestrogens for the Management of Endometriosis: Findings and Issues.

Cai X, Liu M, Zhang B, Zhao S, Jiang S Pharmaceuticals (Basel). 2021; 14(6).

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Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: A review.

Hung S, Zhang R, Tan Z, Chung J, Zhang T, Wang C Med Res Rev. 2021; 41(4):2489-2564.

PMID: 33948974 PMC: 8252000. DOI: 10.1002/med.21802.

An Overview on the Conservative Management of Endometriosis from a Naturopathic Perspective: Phytochemicals and Medicinal Plants.

Balan A, Moga M, Dima L, Dinu C, Martinescu C, Panait D Plants (Basel). 2021; 10(3).

PMID: 33804660 PMC: 8003677. DOI: 10.3390/plants10030587.

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