[8]-Gingerol exerts anti-myocardial ischemic effects in rats via modulation of the MAPK signaling pathway and L-type Ca2+ channels.
Yucong XueMuqing ZhangBin ZhengYuanyuan ZhangXi ChuYu LiuZiliang LiXue HanLi ChuPublished in: Pharmacology research & perspectives (2022)
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 (ICa-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 ICa-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 ICa-L modulation.
Keyphrases
- oxidative stress
- signaling pathway
- induced apoptosis
- diabetic rats
- ischemia reperfusion injury
- pi k akt
- dna damage
- heart rate
- cell death
- left ventricular
- cell cycle arrest
- protein kinase
- poor prognosis
- endoplasmic reticulum stress
- heart failure
- heart rate variability
- epithelial mesenchymal transition
- cell proliferation
- binding protein
- cardiovascular disease
- type diabetes
- stem cells
- intensive care unit
- risk factors
- single cell
- smooth muscle
- combination therapy
- breast cancer cells
- coronary artery disease
- cerebral ischemia
- heat shock
- stress induced
- reactive oxygen species
- label free
- smoking cessation
- acute respiratory distress syndrome