[8]‐Gingerol exerts anti‐myocardial ischemic effects in rats via modulation of the MAPK signaling pathway and L‐type Ca²⁺ channels

Abstract

Myocardial ischemia (MI) remains the leading cause of mortality worldwide. Therefore, it is urgent to seek the treatment to protect the heart. [8]-Gingerol (8-Gin), one of the most active ingredients in ginger, has antioxidant, cardiotonic, and cardiovascular protective properties. The present study elucidated the cardioprotection effects and underlying mechanisms of 8-Gin in isoproterenol (ISO)-induced MI. ISO (85 mg/kg/d) was subcutaneously injected for 2 consecutive days to induce acute MI model in rats. Electrocardiography, oxidative stress levels, calcium concentrations, and apoptosis degree were observed. The effects of 8-Gin on L-type Ca²⁺ current (I_Ca-L ), contraction, and Ca²⁺ transients were monitored in rat myocytes via patch-clamp and IonOptix detection systems. 8-Gin decreased J-point elevation and heart rate and improved pathological heart damage. Moreover, 8-Gin reduced the levels of CK, LDH, and MDA, ROS production, and calcium concentrations in myocardial tissue, while increased the activities of SOD, CAT, and GSH. In addition, 8-Gin down-regulated Caspase-3 and Bax expressions, while up-regulated Bcl-2 expression. 8-Gin produced a marked decrease in the expression of p38, JNK, and ERK1/2 proteins. 8-Gin inhibited I_Ca-L , cell contraction, and Ca²⁺ transients in isolated rat myocytes. The results indicate that 8-Gin could exert anti-myocardial ischemic effects, which may be associated with oxidative stress reduction, cardiomyocytes apoptosis inhibition through MAPK signaling pathway, and Ca²⁺ homeostasis regulation via I_Ca-L modulation.