BushenQiangxin Formula Inhibits Inflammation and Apoptosis in Doxorubicin- Induced Heart Failure via the NF-κB/Bcl-2 Axis.

INTRODUCTION The incidence of chronic heart failure continues to rise annually, making improved prognosis central to reducing its high mortality rate. BushenQiangxin Formula (BSQX) demonstrates significant clinical efficacy, yet its molecular mechanisms for cardiac protection through inhibition of myocardial inflammation and apoptosis remain to be elucidated.

Methods

A doxorubicin-induced rat CHF model was established. The efficacy of the formula was evaluated via echocardiography, Hematoxylin and Eosin (HE) staining, and TUNEL staining. Non-tar-geted serum metabolomics explored altered metabolic profiles, while Western blot and immunohisto-chemical analyses assessed key proteins in the NF-κB/Bcl-2 signaling axis.

Results

BSQX intervention significantly improved Left Ventricular Ejection Fraction (LVEF) in CHF rats while mitigating myocardial tissue injury and apoptosis. Metabolomic analysis revealed that the formula significantly re-regulated dysregulated bile acid metabolic pathways. Molecular mechanism studies confirmed that the formula markedly downregulated proinflammatory factor IL-17 and NF-κB protein expression while upregulating the anti-apoptotic protein Bcl-2 and inhibiting Caspase-9 activation.

Discussion

The ability of BSQX to concurrently restore bile acid metabolic homeostasis and suppress the NF-κB/Bcl-2-mediated inflammatory and apoptotic cascades underscores its multi-target, holistic therapeutic advantage. This regulation of the "metabolism-inflammation-apoptosis" cross-talk provides a novel molecular rationale for its cardioprotective effects against chronic heart failure.

Conclusion

BSQX exerts cardioprotective effects by repairing metabolic dysregulation and inhibiting the NF-κB/Bcl-2 signaling axis, thereby effectively alleviating myocardial inflammation and apoptosis.