10‐Gingerol alleviates hypoxia/reoxygenation‐induced cardiomyocyte injury through inhibition of the Wnt5a/Frizzled‐2 pathway

10-Gingerol (10-Gin), an active ingredient extracted from ginger, has been reported to have beneficial effects on the cardiovascular system. However, 10-Gin has not been proved to offer protection against cardiomyocyte injury induced by hypoxia/reoxygenation (H/R). This study aimed to investigate the protective effects of 10-Gin against H/R-induced injury and its potential mechanisms in cardiomyocytes. A H/R injury model of H9c2 cardiomyocytes was established using 600 μmol/L CoCl₂ to induce hypoxia in the cells for 24 hr and then reoxygenated for 3 hr. 10-Gin was pretreated with H9c2 cardiomyocytes for 24 hr to assess its cardiomyocyte protection. Our results showed that 10-Gin improved the viability of H9c2 cardiomyocytes in the H/R model and decreased the activities of creatine kinase, lactate dehydrogenase, and the generation of reactive oxygen species. By intracellular Ca²⁺ ([Ca²⁺]_i) fluorescence, we found that 10-Gin could significantly reduce the [Ca²⁺]_i concentration. 10-Gin administration increased the activities of antioxidase and reduced malondialdehyde content and inflammatory cytokine levels. 10-Gin also reduced the apoptosis levels. Importantly, 10-Gin administration decreased the gene and protein expressions of Wnt5a and Frizzled-2. In conclusion, 10-Gin alleviates H/R-induced cardiomyocyte injury, which is associated with the antioxidation, anti-inflammation, antiapoptosis action, and reduction of [Ca²⁺]_i overload by suppressing the Wnt5a/Frizzled-2 pathway.