Nimbolide ameliorates fibrosis and inflammation in experimental murine model of bleomycin-induced scleroderma

AbstractBackgroundClinical manifestations of skin fibrosis are very variable and ambiguous, making its management quite critical and challenging. The lack of appropriate established pharmacological interventions make its treatment even more complicated. Intricate details of the underlying pathogenesis are thus imperative to further explore different treatment possibilities. Of note, the TGF- β/Smad signaling axis and epithelial to mesenchymal transition (EMT) are the principal offenders in this fibrotic disorder.ObjectiveOur current study is aimed at demonstrating the antifibrotic and anti-inflammatory potential of nimbolide, a triterpene derived from Indian traditional plant neem, in a murine model of Bleomycin-induced scleroderma.MethodsMale C57BL/6 mice were administered with Bleomycin injections subcutaneously, daily for 28  days, at a constant site on the dorsum of the mice. Treatment with nimbolide lasted from day 1 to day 28. At the time of study termination, the injected sites were collected and stored suitably to conduct further molecular experiments and protein expression studies.Results and conclusionThe results of our study show that nimbolide can significantly intervene in the TGF- β/Smad signaling axis and the consequent EMT process, thus attenuating deposition of extracellular matrix. Nimbolide also profoundly caused the regression of established inflammation-driven fibrosis, thus demonstrating both antifibrotic and anti-inflammatory activities. Another comm...
Source: Inflammopharmacology - Category: Drugs & Pharmacology Source Type: research