Biochanin‐A alleviates fibrosis and inflammation in cardiac injury in mice

Abstract

AbstractBiochanin‐A (BCA), is an isoflavonoid, exhibits protective effects against various diseases. This study was conducted to observe the effect of BCA on isoprenaline (ISP)‐induced cardiac fibrosis and explore the underlying mechanism. The curative effect of BCA was investigated with oral administration for 14 days in ISP‐induced cardiac fibrosis in mice. The fibrotic biomarkers, like collagen I and III, were estimated by ELISA. Commercial kits were used to estimate cholesterol, triglycerides, and creatine kinase‐myocardial band (CK‐MB) levels. The messenger ribonucleic acid (mRNA) expression studies were performed by quantitative real‐time polymerase chain reaction. Gelatin zymography was used to study the expression of matrix metalloproteinases‐2 (MMP‐2). BCA co‐administration significantly improved the morphometric parameters; including heart weight, heart weight to body weight, heart weight to tibial length, and lipid profile. BCA treatment showed a reduction in inflammatory cells and collagen deposition as depicted in the histopathology of heart tissues. The enhanced levels of collagen‐I, III, and hydroxyproline were significantly decreased by BCA co‐treatment, whereas CK‐MB level was reduced slightly. BCA co‐administration increased the activity of reduced glutathione enzyme, showing the antioxidative effects of BCA. BCA treatment significantly reduced interleukin‐6 (Il6) inflammatory cytokine along with partially decreased mRNA expression of fibrotic signaling markers such as natriuretic peptide type B (Nppb), α‐smooth muscle actin (Acta2), connective tissue growth factor (Ctgf), transforming growth factor β (Tgfb), small mothers against decapentaplegic homolog‐3 (Smad‐3). However, BCA did not modify Mmp‐2 expression, which was significantly increased by ISP. In conclusion, BCA exerts an antifibrotic effect by modulating lipid profile, enhancing antioxidant enzyme, and reducing collagen content and inflammation.