Biochanin-A alleviates fibrosis and inflammation in cardiac injury in mice |
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Authors: | Meemansha Sharma Thakur Uttam Singh Abhinav Rana Tarun Kumar Manju Gari Pashupathi Mani Madhu Cholenahalli Lingaraju Subhashree Parida Vidya Singh Monalisa Sahoo Dinesh Kumar |
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Affiliation: | 1. Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India;2. Division of Animal Biochemistry, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India;3. Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India |
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Abstract: | Biochanin-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. |
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Keywords: | biochanin-A cardiac fibrosis mice |
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