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
 
 
 
Highlights
Endometriosis (EM) affects about 10 % of females of reproductive age, and 20 – 50 % of women who have infertility problems and chronic pelvic pain [1]
Withaferin A inhibited the growth of ectopic endometrial tissues
The volume of ectopic tissues was reduced to 11.57 ± 1.01 mm3 in animals that were treated with the withaferin A at 150 mg/kg dosage
Summary
Endometriosis (EM) affects about 10 % of females of reproductive age, and 20 – 50 % of women who have infertility problems and chronic pelvic pain [1]. EM is characterized by presence of endometrium consisting of stroma and glandular tissue outside the uterine cavity [2]. Endometriotic lesions are associated with disintegration of extracellular matrix (ECM), invasion of the peritoneum, and migration of endometrial stromal cells. A better understanding of the signaling pathways and molecular events associated with the initiation and progression of EM aids in the identification of effective therapeutic strategies. Matrix metalloproteinases (MMPs), the proteolytic enzymes [7] are critically involved in coordination and regulation of the physiological functioning of the endometrium. Studies have reported elevated MMPs 2, 3, 7, and 9 in EM [8] and suppression of which inhibited ectopic lesions from human endometrium in mice [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
