6‐Gingerol Activates PI3K/Akt and Inhibits Apoptosis to Attenuate Myocardial Ischemia/Reperfusion Injury

Abstract

6-Gingerol (6-G) is known to alleviate myocardial ischemia/reperfusion injury. However, the underlying molecular mechanisms of 6-G myocardial protection are not known. In this study, the protective effect of 6-G on ischemia/reperfusion (I/R) damage and whether such a mechanism was related to apoptosis inhibition and activation of phosphoinositide 3-kinases (PI3K)/serine/threonine kinase (Akt) signaling pathway were investigated. Rats were subjected to I/R in the presence or absence of 6-G and the changes of cardiac function, infarct size and histopathological changes, and the levels of cardiac troponin T, creatine kinase-MB, and myocardial apoptosis were examined. The expression of caspase-3, PI3K, p-Akt, and Akt was also determined. We found that 6-G (6 mg/kg) pretreatment significantly improved heart function and ameliorated infarct size and histopathological changes and cardiac troponin T and creatine kinase-MB levels induced by I/R. Moreover, pretreatment with 6-G significantly inhibited myocardial apoptosis and caspase-3 activation induced by I/R. 6-G also upregulated expression of PI3K, p-Akt, and Akt in myocardial tissues. Taken together, these findings suggest that 6-G inhibits apoptosis and activates PI3K/Akt signaling in response to myocardial I/R injury as a possible mechanism to attenuate I/R-induced injury in heart. These results might be important for developing novel strategies for preventing myocardial I/R injury.

6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3

“…Meanwhile, it was obviously seen from results that these trends were attenuated by 6G, suggesting that 6G might decrease hypoxia-induced PC-12 cells injuries through repressing apoptosis and autophagy. Similarly, previous studies reported that 6G inhibited apoptosis in response to myocardial ischemia/reperfusion (I/R) injury as a possible mechanism to attenuate I/R-induced injury in the heart [8]. Besides that, the neuroprotective effects of 6G have been reported in scopolamine-induced amnesia in C57BL/6 mice [22].…”

“…6-Gingerols (6G), which is a phenolic ingredient purified from ginger, has been reported to exert anti-inflammation, anti-oxidative and anti-apoptotic roles [5][6][7]. 6G is reported to alleviate myocardial ischemia/reperfusion injury [8]. 6G can also reduce the levels of inflammatory markers, making it a potential strategy for the treatment of atherosclerosis [9].…”

6-Gingerol protects cardiocytes H9c2 against hypoxia-induced injury by suppressing BNIP3 expression

“…For example, Li et al have corroborated that 6 G exerts protective effects against hypoxia/reoxygenation-induced injury in intestinal mucosa [20]. Interestingly, an experimental study has validated that pretreatment with 6 G ameliorates myocardial injury induced by hypoxia/reoxygenation [21].…”

6‐Gingerol, an active pungent component of ginger, inhibits L‐type Ca2+ current, contractility, and Ca2+ transients in isolated rat ventricular myocytes

“…It has diverse and interesting pharmacological effects including antipyretic, anti‐inflammatory, anti‐angiogenic, anti‐cancer, cardio‐tonic, and anti‐aging effects. It inhibits spontaneous motor activity and prostaglandin biosynthesis (Ajayi, Adedara, & Farombi, ; Dugasani et al, ; Kim et al, ; Kiuchi, Iwakami, Shibuya, Hanaoka, & Sankawa, ; Lee et al, ; Lee, Seo, Kang, & Kim, ; Lv et al, ; Suekawa et al, ; Tahir et al, ).…”