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

Abstract

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.

Mechanistic insights into the ameliorative effects of hypoxia-induced myocardial injury by Corydalis yanhusuo total alkaloids: based on network pharmacology and experiment verification

“…The experimental subjects in this study consisted of cells isolated from the internal environment and H9c2 cells, thereby limiting the ability to fully replicate the complex physiological milieu in vivo . The H9c2 cells, despite sharing similar physiological and biochemical characteristics with primary cardiomyocytes, still exhibit distinctions in terms of cellular morphology, contractility, and gene expression ( Zheng et al, 2021 ). Different species of animal experiments are needed to verify the protective effect of CYTA on MI.…”