Phytomedicine. 2026 Oct 23;162:158878. doi: 10.1016/j.phymed.2026.158878. Online ahead of print.
ABSTRACT
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.
PMID:42966160 | DOI:10.1016/j.phymed.2026.158878