Tanshinone IIA alleviates acute ethanol-induced myocardial apoptosis mainly through inhibiting the expression of PDCD4 and activating the PI3K/Akt pathway

Myocardial apoptosis contributes to acute ethanol-induced cardiac injury. Improving immoderate apoptosis has become the potential therapeutic strategy for acute ethanol-induced heart damage. Previous studies reported that Tanshinone IIA (Tan IIA), a key ingredient extracted from Salvia miltiorrhiza Bunge, performed an anti-apoptotic role against acute ethanol-related cell damage. In this study, we investigated whether Tan IIA protected the acute ethanol-induced cardiac damage in vivo and in vitro. C57BL/6 mice were treated with acute ethanol and then treated with Tan IIA. The results showed that Tan IIA significantly improved heart function and blocked myocardial apoptosis. Acute ethanol exposure induced H9C2 cells apoptosis. Treatment with Tan IIA abrogated acute ethanol-induced H9C2 cells apoptosis. Mechanistically, Tan IIA inhibited apoptosis by downregulating the programmed cell death protein 4 (PDCD4) expression and activating the phosphoinositide 3-kinase (PI3K)/Akt pathway. Furthermore, PDCD4 overexpression abrogated Tan IIA-mediated anti-apoptotic role and activation on the PI3K/Akt pathway. Interestingly, the PI3K inhibitor (LY294002) application significantly attenuated the main protective effects of Tan IIA. In conclusion, Tan IIA improves acute ethanol-induced myocardial apoptosis mainly through regulating the PDCD4 expression and activating the PI3K/Akt signaling pathway. We provide evidence that Tan IIA is a new treatment approach for acute ethanol-induced heart damage.