Honokiol Inhibits Tumor Necrosis Factor-α-Stimulated Rat Aortic Smooth Muscle Cell Proliferation via Caspase- and Mitochondrial-Dependent Apoptosis

This study aims to investigate the effects of honokiol on proliferation, cell cycle, and apoptosis in tumor necrosis factor (TNF)-alpha-induced rat aortic smooth muscle cells (RASMCs). We found that honokiol treatment showed potent inhibitory effects on TNF-alpha-induced RASMC proliferation, which were associated with G0/G1 cell cycle arrest and downregulation of cell cycle-related proteins, including cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2 and CDK4. Furthermore, honokiol treatment led to the release of cytochrome c into cytosol and a loss of mitochondrial membrane potential (Delta Im), as well as a decrease in the expression of Bcl-2 and an increase in the expression of Bax. Treatment with honokiol also reduced TNF-alpha-induced phosphorylation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase. Taken together, our results suggest that honokiol suppresses TNF-alpha-stimulated RASMC proliferation via caspase- and mitochondria-dependent apoptosis and highlight the therapeutic potential of honokiol in the prevention of cardiovascular diseases.