Qishen Yangxin Granule ameliorates cardiac function and ventricular remodeling in dilated cardiomyopathy by attenuating inflammation and myocardial fibrosis

Background Qishen Yangxin Granule (QSYX), a clinically utilized traditional Chinese medicinal formula, has demonstrated therapeutic efficacy for cardiovascular diseases. However, its cardioprotective mechanism in dilated cardiomyopathy (DCM) remains incompletely defined. Purpose To evaluate the therapeutic efficacy of QSYX against DCM and the associated anti-inflammatory and anti-fibrotic mechanisms. Methods Cardioprotective effects of QSYX were assessed both in vivo using a doxorubicin-induced DCM rat model and in vitro using rat cardiac fibroblasts stimulated with lipopolysaccharide. Evaluations included cardiac function, histopathological analysis, levels of inflammatory factors, and myocardial fibrosis markers. Single-cell RNA sequencing was employed to explore the potential mechanism of QSYX-mediated improvement in cardiac structure and function. Modulation of the toll-like receptor 4 (TLR4)/p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-κB (NF-κB) pathway was examined via western blot, immunohistochemistry, confocal laser scanning microscope, and real-time reverse transcription-PCR. The specific p38 MAPK agonist LY188011 was used to verify the dependence of QSYX effect on the TLR4/p38 MAPK/NF-κB signaling pathway. Results QSYX administration improved cardiac function in DCM rats, accompanied by significant attenuation of cardiomyocyte hypertrophy, apoptosis, inflammatory cell infiltration, and collagen deposition. Comparable protective effects were observed in lipopolysaccharide-treated cardiac fibroblasts. Mechanistically, QSYX suppressed lipopolysaccharide-induced upregulation of TLR4, p38 MAPK, and NF-κB p65 and downregulated the expression of inflammatory factors and myocardial fibrosis markers. Furthermore, intervention with LY188011 confirmed that the cardioprotective effects of QSYX are mediated through suppression of the TLR4/p38 MAPK/NF-κB signaling pathway. Conclusion QSYX attenuates myocardial inflammation and fibrosis primarily through inhibition of the TLR4/p38 MAPK/NF-κB signaling pathway, thereby exerting cardioprotective effects against DCM-induced cardiac injury.