Hesperetin ameliorates ischemia/hypoxia‐induced myocardium injury via inhibition of oxidative stress, apoptosis, and regulation of Ca2+ homeostasis

Ischemia/hypoxia (I/H)‐induced myocardial injury has a large burden worldwide. Hesperetin (HSP) has a cardioprotective effect, but the molecular mechanism underlying this is not clearly established. Here, we focused on the protective mechanisms of HSP against I/H‐induced myocardium injury. H9c2 cardiomyocytes were challenged with CoCl2 for 22 h to imitate hypoxia after treatment groups received HSP for 4 h. The viability of H9c2 cardiomyocytes was evaluated, and cardiac function indices, reactive oxygen species, apoptosis, mitochondrial membrane potential (MMP), and intracellular Ca2+ concentration ([Ca2+]i) were measured. L‐type Ca2+ current (ICa‐L), myocardial contraction, and Ca2+ transients in isolated ventricular myocytes were also recorded. We found that HSP significantly increased the cell viability, and MMP while significantly decreasing cardiac impairment, oxidative stress, apoptosis, and [Ca2+]i caused by CoCl2. Furthermore, HSP markedly attenuated ICa‐L, myocardial contraction, and Ca2+ transients in a concentration‐dependent manner. Our findings suggest a protective mechanism of HSP on I/H‐induced myocardium injury by restoring oxidative balance, inhibiting apoptosis, improving mitochondrial function, and reducing Ca2+ influx via L‐type Ca2+ channels (LTCCs). These data provide a new direction for HSP applied research as a LTCC inhibitor against I/H‐induced myocardium injury.