Salvianolic acid B improves autophagic dysfunction and decreases the apoptosis of cholesterol crystal-induced macrophages via inhibiting the Akt/mTOR signaling pathway

Progressive macrophage dysfunction and apoptosis are some of the major events that occur during atherogenesis. To further investigate the intrinsic association between atherosclerosis (AS) and macrophage apoptosis and autophagy, cholesterol crystals (CHCs) were used to stimulate RAW264.7 macrophages to establish a macrophage model of advanced AS. Cells in the CHC group were treated with salvianolic acid B (Sal B) to evaluate its protective effects and reveal its underlying molecular mechanism. The results demonstrated that treatments with Sal B significantly improved autophagy dysfunction and reduced the apoptotic rate of CHC-induced macrophages. Furthermore, Sal B significantly attenuated CHC-induced release of proinflammatory factors (TNF-alpha and IL-6) by macrophages. Treatment of macrophages with a specific inhibitor of autophagy (3-methyladenine) significantly reversed Sal B-mediated effects on autophagy, suggesting that Sal B-induced autophagy may display a protective effect in CHC-induced macrophages. Furthermore, pretreatment of CHC-induced macrophages with insulin significantly decreased Sal B-induced autophagy, indicating that the Akt/mTOR signaling pathway may serve as a critical mediator in regulating Sal B-mediated cell death. Taken together, the present study demonstrated that Sal B improved autophagic dysfunction and reduced the apoptosis of CHC-induced macrophages via inhibiting the Akt/mTOR signaling pathway.