{"paper_id":"971e94dd-f0f8-4e15-a380-75649793933f","body_text":"Main Article Content\nWithaferin A downregulates COX-2/NF-κB signaling and modulates MMP-2/9 in experimental endometriosis\nAbstract\nPurpose: To study the effect of withaferin A on an experimentally-induced endometriosis (EM) model.\nMethods: Female Sprague-Dawley rats were induced EM by implantation of autologous endometrium. Rats in the treatment group were administered withaferin A orally for 30 days. A separate group of rats that was administered gestrinone (GTN) served as positive control.\nResults: Withaferin A treatment reduced the spherical volume of the ecto-uterine tissue was following five weeks after implantation. Histological analysis revealed regression of the lesions and restoration of normal architecture. Withaferin A effectively down-regulated the expressions and activities of matrix metalloproteinases (MMPs) 2 and 9 in the ectopic endometrium. The activities of MMPs-2 and 9 significantly (p<0.05) decreased from 1.79- and 1.65-fold to 1.08- and 1.1-fold, respectively. The EM- induced up-regulation of NF-κB/COX-2 signaling was down-regulated by withaferin A. The levels of Cox-2 decreased significantly (p < 0.05) from 198 % in EM control rats to 122.7 % in 150 mg withaferin A treated EM-induced rats. The increased levels of major inflammatory mediators nitric oxide (NO), TNF-α, Interleukins (IL) - IL-1β and IL-6, markedly (p < 0.05) were reduced by withaferin A treatment, when compared to EM control group.\nConclusion: Withaferin A effectively suppresses the proliferation of lesions and modulates the immune responses-associated expressions of COX-2, NF-κB and matrix metalloproteinases (MMPs), viz, MMP- 2 and MMP-9","source_license":"CC0","license_restricted":false}