Magnesium lithospermate B improves myocardial function and prevents simulated ischemia/reperfusion injury-induced H9c2 cardiomyocytes apoptosis through Akt-dependent pathway

Abstract

Ethnopharmacological relevance: Magnesium lithospermate B (MLB), an active polyphenol acid of Radix Salviae Miltiorrhizae (Danshen), showed a wide range of pharmacological activities in cardiovascular diseases. However, its role in protection against ischemia/reperfusion injury in H9c2 cardiomyocytes has not been elucidated. This study was aimed to investigate the protective effect and potential molecular mechanisms of MLB on apoptosis in H9c2 cardiomyocytes in vitro.

Materials and methods: We tested cell viability, shortening amplitude, necrosis, apoptosis, and the expression levels of Akt, phosphorylated Akt, Bcl-2 and Bax after 2-h simulated ischemia and 24-h simulated reperfusion in H9c2 cardiomyocytes. We further observed the contractile function in hearts after they were subjected to global 30-min ischemia and 180-min reperfusion.

Results: Pretreatment with MLB markedly increased cell viability and while reducing evidence of necrosis and apoptosis in H9c2 cardiomyocytes. In addition, the expression of Bcl-2 and Bax protein was modulated. The results also showed that MLB significantly increased phosphorylation of Akt and that this phosphorylation can be partially inhibited by phosphoinositide 3-kinase/Akt inhibitor. Furthermore, MLB improved MI/R-induced myocardial contractile function.

Conclusion: Our results showed that MLB prevents I/R-induced myocardial damage by reducing necrosis and apoptosis in H9c2 cardiomyocytes and improving myocardial function in rat hearts.

Keywords: Akt; Apoptosis; CK-MB; Cardioprotection; ELISA; Ischemia/reperfusion; LDH; MI/R; MLB; Magnesium lithospermate B; OGD; SI/R; creatine phosphokinase-MB; enzyme-linked immunosorbent assay; lactate dehydrogenase; magnesium lithospermate B; myocardial ischemia/reperfusion; oxygen and glucose deprived; simulated ischemia/reperfusion.