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

Dan Wang, Jiang Yiling, Yiling Jiang, Li Chun, Jing Fan, Wang Huimin, Huimin Wang, Xiaoxin Yang
In: Tropical Journal of Pharmaceutical Research · 2022 · vol. 20(2) , pp. 239–248 · doi:10.4314/tjpr.v20i2.3 · W4205497534
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Withaferin A reduced endometriosis lesion volume and modulated inflammatory markers by downregulating COX-2/NF-κB signaling and matrix metalloproteinases-2 and -9.

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This study investigated the therapeutic potential of withaferin A in a rat model of surgically induced endometriosis. Treatment with the compound significantly reduced the volume of ectopic uterine tissue and restored normal histological architecture compared to controls. Mechanistically, withaferin A suppressed lesion proliferation by downregulating the NF-κB/COX-2 signaling pathway and decreasing the activity of matrix metalloproteinases MMP-2 and MMP-9. The treatment also markedly lowered levels of inflammatory mediators including nitric oxide, TNF-α, and various interleukins within the ectopic endometrium. This paper is centrally about endometriosis — specifically evaluating the anti-inflammatory and anti-proliferative effects of withaferin A on experimental lesions.

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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
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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

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Condition tags

endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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