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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⚙ AI-generated deep summary by qwen3.7-flash, 2026-08-21 · read from full text ⓘ

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 (2-hop)

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. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (27)

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