Puerarin Suppresses Invasion and Vascularization of Endometriosis Tissue Stimulated by 17β-Estradiol

Dan Wang, Yuhuan Liu, Jie Han, Dongxia Zai, Mei Ji, Wen Cheng, Ling Xu, Luxi Yang, Miaoxia He, Jian Ni, Zailong Cai, Chaoqin Yu
PloS one · 2011 · vol. 6(9) , pp. e25011 · doi:10.1371/journal.pone.0025011 · PMID:21949833 · W2064010277
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Puerarin reversed 17β-estradiol-induced endometriotic stromal cell invasion by modulating MMP-9 and TIMP-1, and inhibited E2-stimulated vascularization in a chicken chorioallantoic membrane assay.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 ⓘ

Wang et al. studied whether puerarin, a weak phytoestrogen, could counteract 17β-estradiol (E2)–driven invasion and vascularization of endometriotic tissue, using cultured endometriotic stromal cells (ESCs) and assays of extracellular matrix invasion (Transwell), protein expression (western blot and immunohistochemistry), and angiogenesis (chick chorioallantoic membrane, CAM). They found that E2 increased ESC invasiveness and shifted the balance toward higher MMP-9 and lower TIMP-1, along with increased MMP-9, ICAM-1, and VEGF and decreased TIMP-1 in E2-stimulated xenografts, whereas co-treatment with puerarin reversed these effects and reduced CAM neovascularization. The paper’s main limitation is that it relies on in vitro/in vivo xenograft and CAM models rather than clinical or patient-derived interventions, and ESCs were assessed specifically for stromal invasion rather than whole-lesion behavior. This paper is centrally about endometriosis — it tests puerarin’s ability to suppress E2-stimulated invasion and angiogenesis of endometriotic tissue.

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Abstract

BACKGROUND: Puerarin, a phytoestrogen with a weak estrogenic effect, binds to estrogen receptors, thereby competing with 17β-estradiol (E2) and producing an anti-estrogenic effect. This study was to investigate whether puerarin could suppress the invasion and vascularization of E2-stimulated endometriotic tissue. METHODOLOGY/PRINCIPAL FINDINGS: The endometriotic stromal cells (ESCs) were successfully established and their invasive ability under different treatments was assessed through a Transwell Assay. Simultaneously, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected by western blotting. Vascularization of endometriotic tissues was observed by chicken chorioallantoic membrane (CAM) assay. The staining of MMP-9, intercellular adhesion molecule 1 (ICAM-1), TIMP-1, and vascular endothelial growth factor (VEGF) in grafted endometriotic tissues was examined using immunohistochemistry analysis. The purity of ESCs in isolated cells was >95%, as determined by the fluoroimmunoassay of vimentin. E2 (10(-8) mol/L) promoted the invasiveness of ESCs by increasing MMP-9 accumulation and decreasing TIMP-1 accumulation. Interestingly, puerarin (10(-9) mol/L) significantly reversed these effects (P<0.01). The CAM assay indicated that puerarin (10(-9) mol/L) also inhibited the angiopoiesis of endometriotic tissue stimulated by the E2 (10(-8) mol/L) treatment (P<0.05). Accordingly, immunohistochemistry showed that the accumulation of MMP-9, ICAM-1, and VEGF was reduced whereas that of TIMP-1 increased in the combination treatment group compared with the E2 treatment group. CONCLUSIONS/SIGNIFICANCE: This study demonstrated that puerarin could suppress the tissue invasion by ESCs and the vascularization of ectopic endometrial tissues stimulated by E2, suggesting that puerarin may be a potential drug for the treatment of endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Estradiol Isoflavones Neovascularization, Pathologic Vasodilator Agents Animals Blotting, Western Cell Adhesion Cell Movement Cell Proliferation Chickens Chorioallantoic Membrane Chorioallantoic Membrane Endometriosis Endometriosis Endometrium Endometrium Endometrium Estradiol

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