Network pharmacology and experimental evaluation of Sanwei Tanxiang Tangsan in doxorubicin-induced heart failure

Heart failure (HF) is a complex syndrome characterized by inflammation, oxidative stress, and cardiomyocyte apoptosis, for which effective and well-tolerated therapies remain limited. This study sought to explore the potential mechanisms by which Mongolian medicine Sanwei Tanxiang Tangsan (STX) may be associated with AKT1/p53-related signaling in the mitigation of HF, employing network pharmacology, molecular docking, and animal experimentation.

Active constituents and corresponding targets of Mongolian medicine STX were systematically screened, followed by the construction of drug–disease interaction networks to identify pivotal proteins and pathways. A doxorubicin-induced HF rat model was established, and after four weeks of intragastric administration of Mongolian medicine STX and sacubitril/valsartan (angiotensin receptor–neprilysin inhibitor, positive control), cardiac functional parameters and expression levels of AKT protein 1 (AKT1), interleukin-6 (IL-6), and p53 were assessed.

Nineteen active components were identified in Mongolian medicine STX, interacting with 153 HF-associated targets, among which AKT1, IL-6, and TP53 served as the core genes. Molecular docking analysis revealed that quercetin and luteolin possessed moderate predicted binding affinities and stable interactions with the corresponding targets. Animal experiments indicated that Mongolian medicine STX significantly reduced N-terminal pro-brain natriuretic peptide levels and altered myocardial AKT1, IL-6, and p53 protein abundance. However, echocardiographic parameters showed no statistically significant improvement compared with the Model group.

Mongolian medicine STX may exert cardioprotective effects in HF, as reflected by improvements in biochemical and histopathological indicators, and these effects may be associated with AKT1/p53-related signaling pathways. However, direct pathway activation and causal mechanisms were not confirmed in the present study and require further investigation.