Cardioprotective effect of phytosterol stigmasterol supplementation against doxorubicin-induced cardiotoxicity

Stigmasterol, a phytosterol abundantly found in various plant sources, including soybeans and other legumes, plays a significant pharmaceutical role due to its pharmacological properties. Research suggests that stigmasterol exhibits anti-inflammatory, antioxidant, and cholesterol-lowering effects, making it a promising candidate for managing cardiovascular disorders. In this work, we elucidated the cardioprotective potency of stigmasterol against doxorubicin-induced cardiotoxicity in rats. Hence we have evaluated the potency of stigmasterol supplementation in preventing doxorubicin-induced cardiotoxicity. Male Wistar rats were treated with doxorubicin (2.5 mg/kg) and supplemented with 25 and 50 mg/kg doses of stigmasterol for 14 days. On 14th day of treatment tail-cuff plethysmography was conducted to assess the hemodynamic parameters. The concentrations of oxidative stress markers, cardiac function markers, myocardial damage markers, and inflammatory biomarkers were assessed in the experimental rats using the commercial kits. The heart tissues were subjected to the histopathological analysis. Docking study was also conducted with NF-κB. The stigmasterol treatment effectively increased the body weight and heart weight and elevated the hemodynamic parameters in doxorubinin-induced rats. The stigmasterol treatment also decreased the oxidative stress via increasing antioxidants, reduced the cardiac function markers, and decreased the myocardial damage markers in the doxorubicin-induced rats. Furthermore, the stigmasterol treatment also reduced the inflammatory markers in the doxorubicin-induced rats. The cardioprotective properties of the stigmasterol was further supported by the results of histopathological analysis and docking analysis where it showed excellent binding affinity for NF-κB. The results of tail-cuff plethysmography and cardiac tissue histopathological analysis authentically proved the inhibitory effect of stigmasterol against doxorubicin induced cardiotoxicity. To conclude supplementation with phytochemical stigmasterol persuasively ameliorated doxorubicin induced cardiotoxicity.