title: Puerarin suppresses invasion and vascularization of endometriosis tissue stimulated by 17β-estradiol.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.forename: Dongxia
authors.initials: D
authors.lastname: Zai
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Luxi
authors.initials: L
authors.lastname: Yang
authors.forename: Miaoxia
authors.initials: M
authors.lastname: He
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
authors.forename: Zailong
authors.initials: Z
authors.lastname: Cai
authors.forename: Chaoqin
authors.initials: C
authors.lastname: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000378:metabolism; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011960:Receptors, Estrogen / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004967:Estrogens; D007529:Isoflavones; D011960:Receptors, Estrogen; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D004958:Estradiol; D020780:Matrix Metalloproteinase 9; C033607:puerarin