Jianxin granules enhance autophagic flux and reduce apoptosis in heart failure via mTOR pathway: A preclinical investigation.

摘要

BACKGROUND: Heart failure (HF) is a leading cardiovascular disease worldwide. Jianxin Granule, a traditional Chinese medicine formula, has been clinically shown to improve cardiac function, yet its molecular mechanism remains unclear. Autophagy is crucial for maintaining cardiac homeostasis, and the mTOR pathway is a central negative regulator of autophagy. OBJECTIVES: To investigate whether Jianxin Granule confers cardioprotection in HF by modulating mTOR signaling to enhance autophagy and suppress apoptosis. Both in vivo and in vitro experiments were performed. METHODS: In male Sprague-Dawley rats HF model and in H9C2 cardiomyocytes exposed to H2O2, autophagy-related proteins and apoptotic markers were assessed by Western blotting and qRT-PCR. The specific role of mTOR signaling was further examined in cardiomyocytes transfected with mTOR-siRNA. RESULTS: Jianxin Granule markedly increased autophagic flux and reduced apoptosis in HF rats and these effects were attenuated by the autophagy inhibitor 3-methyladenine (3-MA). Consistent findings were observed in H2O2-injured H9C2 cells, where Jianxin Granule promoted autophagy and decreased apoptosis. In mTOR-siRNA-transfected cells, Jianxin Granule further enhanced autophagic flux and diminished apoptosis, supporting the involvement of mTOR signaling in its protective mechanism. CONCLUSION: Jianxin Granule protects against HF by regulating the mTOR pathway, thereby boosting autophagic flux and reducing cardiomyocyte apoptosis. These results provide mechanistic support for its clinical application in heart failure.