Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Withaferin A downregulates COX-2/NF-κB signaling and modulates MMP-2/9 in experimental endometriosis

Wang Dan¹, Jiang Yiling², Li Chun¹, Fan Jing¹, Wang Huimin¹, Yang Xiaoxin¹

¹Department of Obstetrics and Gynecology, Wuhan Third Hospital-Tongren Hospital of WuHan University, Wuhan 430060; ²Department of Obstetrics and Gynecology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan 430015, China.

For correspondence:- Yang Xiaoxin Email: ValeryMagitt@yahoo.com Tel:+862788843447

Accepted: 16 January 2021 Published: 28 February 2021

Citation: Dan W, Yiling J, Chun L, Jing F, Huimin W, Xiaoxin Y. Withaferin A downregulates COX-2/NF-κB signaling and modulates MMP-2/9 in experimental endometriosis. Trop J Pharm Res 2021; 20(2):239-248 doi: 10.4314/tjpr.v20i2.3

© 2021 The authors.
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Abstract

Purpose: To study the effect of withaferin A on an experimentally-induced endometriosis (EM) model.

Methods: 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.

Results: 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.

Conclusion: 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

Keywords: Endometriosis, Inflammation, Matrix metalloproteinases, Nuclear factor-?B signaling, Withaferin A