Xin-II shows cardioprotective effects in a rat model of chronic heart failure: An integrated network pharmacology and transcriptomic

BACKGROUNDChronic heart failure (CHF) is a major global public health burden.Mongolian Medicine Xin-II has shown promising clinical efficacy in the management of cardiovascular diseases, including coronary heart disease and arrhythmias.However, its underlying molecular mechanisms remain poorly understood. AIMTo evaluate the therapeutic effects of Xin-II on CHF and investigate the potential molecular pathways underlying these effects using an integrated approach combining network pharmacology and transcriptomic sequencing. METHODSA rat model of CHF was established to assess the therapeutic efficacy of Xin-II.Network pharmacology was used to screen the active components of Xin-II and predict its potential therapeutic targets and key signaling pathways implicated in CHF.Transcriptomic sequencing (RNA-seq) was performed to characterize druginduced changes in gene expression and further verify the regulatory patterns of candidate signaling pathways identified by network pharmacology. RESULTSXin-II improved cardiac function and mitigated myocardial pathological lesions in rats with CHF.Transcriptomic analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment identified the peroxisome proliferator-activated receptor (PPAR) signaling pathway as the most significantly enriched pathway, suggesting its potential involvement in the therapeutic effects of Xin-II against CHF.Mechanistically, Xin-II modulated the expression of key genes and proteins associated with the PPAR/hypoxia-inducible factor-1 alpha signaling cascade.These findings suggest that Xin-II attenuates CHF through multitarget regulation, with the 4 / 44 PPAR/hypoxia-inducible factor-1 alpha axis potentially highlighting an important mechanistic pathway. CONCLUSIONThis study found that Xin-II ameliorates CHF through multi-target molecular mechanisms, thereby providing insights into the therapeutic effects of Xin-II and supporting its further investigation as a treatment for CHF.Further, these findings establish a valuable paradigm to advance the modernization and broader application of traditional Mongolian medicine.