Abstract
Objective
Chronic heart failure (CHF) is characterized by progressive cardiac dysfunction, myocardial remodeling, apoptosis, and metabolic disturbance. Xinmailong injection (XML) has demonstrated therapeutic potential for CHF; however, its underlying mechanisms remain incompletely understood.Methods
A total of 40 SPF rats were used to establish a doxorubicin-induced CHF model, with another 8 rats serving as the normal control group. The model rats were randomized into 5 groups (n = 8 per group): model, digoxin (0.025 mg/kg), XML low- (60 mg/kg), XML medium- (120 mg/kg), XML high- (240 mg/kg) groups with a 2-week intervention. Cardiac function, serum biomarkers, histopathology and cardiomyocyte apoptosis were detected. Untargeted metabolomics, network pharmacology, molecular docking and in vivo validation were integrated to explore the mechanisms of XML.Results
XML dose-dependently elevated left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP) and maximum rate of left ventricular pressure change (± dp/dtmax), while reducing left ventricular end-diastolic pressure (LVEDP) (P Conclusion
XML ameliorates doxorubicin-induced CHF via improving cardiac function, mitigating myocardial injury/fibrosis, restoring metabolic homeostasis and inhibiting cardiomyocyte apoptosis, which is closely related to regulating the SIRT1/caspase-3 axis and multiple metabolic pathways.