{"paper_id":"c291254f-9ddc-4a66-b3e0-2c2c382cb19c","body_text":"Worked equally on this study.\nAbstract\nPhytoestrogens, which have a weak estrogenic effect, bind to estrogen receptors (ERs), thereby competing with estradiol, have an antiestrogenic effect on women of reproductive age with high estrogenic level. Herein, we examined the ability of the phytoestrogen Puerarin to treat endometriosis in rat models of endometriosis. In total, 75 adult, mature female Sprague-Dawley rats in which endometriotic implants were successfully induced by transplanting autologous endometrial tissue to ectopic sites were used in this study. Oral gavage of Puerarin (at doses of 600, 200, or 60 mg/kg per day) or Danazol (80 mg/kg per day) started 4 weeks after implantation. Control model rats received vehicle alone. After administration for 4 weeks, the weight of the ectopic implants, estradiol concentration, as well as ER-α and Aromatase P450 (P450arom) expression in different groups of rat tissues were evaluated after treatment. The endometriotic tissue weight and serum estrogen levels were significantly lower in high, medium, low dose of Puerarin and Danazol treatment groups than that in control group (P < .05 orP < .01). Low-dose Puerarin inhibited P450arom expression and significantly reduced estrogen levels in endometriotic tissue (P < .01). Three doses of Puerarin had no adverse effects on liver, kidney, and ovary, whereas high-dose Puerarin administration caused thinner bone trabecula with distortion and breakage and Danazol administration caused mild or moderate hepatic cell damage. These data demonstrate that Puerarin was able to effectively suppress the growth and development of ectopic endometrium in the rat endometriosis model, even at low doses, suggesting it may be an effective treatment for endometriosis.\nSimilar content being viewed by others\nReferences\nRanney B. Etiology, prevention and inhibition of endometriosis. Clin Obstet Gynecol. 1980;23(3):875–881.\nFanfani F, Fagotti A, Ferrandina G, Bifulco G, Legge F, Lorusso D. Increased cyclooxygenase-2 expression is associated with better clinical outcome in patients submitted to complete ablation for severe endometriosis. Hum Reprod. 2005;20(10):2964–2968.\nNoble LS, Simpson ER, Johns A, Bulun SE. Aromatase expression in endometriosis. J Clin Endocrinol Metab. 1996;81(1):174–179.\nNoble LS, Takayama K, Zeitoun KM, et al. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab. 1997;82(2):600–606.\nVelasco I, Rueda J, Acien P. Aromatase expression in endometriotic tissues and cell cultures of patients with endometriosis. Mol Hum Reprod. 2006;12(6):377–381.\nMatsuzaki S, Canis M, Pouly JL, Dechelotte PJ, Mage G. Analysis of aromatase and 17beta-hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid expression in deep endometriosis and eutopic endometrium using laser capture microdissection. Fertil Steril. 2006;5(2):308–313.\nSimpson ER, Mahendroo MS, Means GD, et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev. 1994;15(3):342–355.\nFatemi HM, Al-Turki HA, Papanikolaou EG, Kosmas L, Desutter P, Devroey P. Successful treatment of an aggressive recurrent post-menopausal endometriosis with an aromatase inhibitor. Reprod Biomed. 2005;11(4):455–457.\nUsui T. Pharmaceutical prospects of phytoestrogens. Endocr J. 2006;53(1):7–20.\nKuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S. Gustafsson JA. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997;138(3):863–870.\nShi SF, Yu CQ. Progress in research on phytoestrogens and their effect targets. Chin J Integr Med. 2005;3(5):408–410.\nKrazeisen A, Breitling R, Möller G, Adamski J. Phytoestrogens inhibit human 17β-hydroxysteroid dehydrogenase type 5. Mol Cell Endocrinol. 2001;171(1–2):151–162.\nLe Bail JC, Champavier Y, Chulia AJ, Habrioux G. Effects of phytoestrogens on aromatase, 3β and 7β-hydroxysteroid dehydrogenase activities and human breast cancer cells. Life Sci. 2000;66(14):1281–1291.\nWhitehead SA, Lacey M. Phytoestrogens inhibit aromatase but not 17β-hydroxysteroid dehydrogenase (HSD) type 1 in human granulosa-luteal cells: evidence for FSH induction of 17β-HSD. Hum Reprod. 2003;18(3):487–494.\nLucas EA, Wild RD, Hammond LJ, et al. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in post-menopausal women. J Clin Endocrinol Metab. 2002;87(4): 1527–1532.\nLemay A, Dodin S, Kadri N, Jacques H, Forest JC. Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Obstet Gynecol. 2002;100(3): 495–504.\nKilkkinen A, Virtamo J, Vartiainen E, et al. Serum enterolactone concentration is not associated with breast cancer risk in a nested case-control study. Int J Cancer. 2004;108(2):277–280.\nShu XO, Zheng Y, Cai H, et al. Soy food intake and breast cancer survival. JAMA. 2009;302(22):2437–2443.\nYu CQ, Yu J, Han J, Zhou QL, Shen W. Regulatory mechanism of malignant behavior of endometriosis mediated by puerarin. Zhong Xi Yi Jie He Xue Bao. 2009;7(1):41–47.\nYu CQ, Li YW, Chen H, Yang SS, Xie GR. Decreased expression of aromatase in the Ishikawa and RL95-2 cells by the isoflavone, puerarin, is associated withinhibition of c-jun expression and AP-1 activity. Food Chem Toxicol. 2008;46(12):3671–3676.\nBerkley KJ, Dmitrieva N, Curtis KS, Papka RE. Innervation of ectopic endometrium in a rat model of endometriosis. PNAS. 2004;101(30):11094–11098.\nMatsuzaki S, Canis M, Darcha C, Dallel R, Okamura K, Mage G. Cyclooxygenase-2 selective inhibitor prevents implantation of eutopic endometrium to ectopic sites in rats. Fert Steril. 2004; 82(6):1609–1615.\nColette S, Lousse JC, Defrère S, et al. Absence of aromatase protein and mRNA expression in endometriosis. Hum Reprod. 2009;24(9):2133–2141.\nAuthor information\nAuthors and Affiliations\nCorresponding authors\nRights and permissions\nAbout this article\nCite this article\nChen, Y., Chen, C., Shi, S. et al. Endometriotic Implants Regress in Rat Models Treated With Puerarin by Decreasing Estradiol Level. Reprod. Sci. 18, 886–891 (2011). https://doi.org/10.1177/1933719111398500\nPublished:\nIssue date:\nDOI: https://doi.org/10.1177/1933719111398500","source_license":"public-domain-us","license_restricted":false}