Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 104, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2022.108975
Keywords
6-Gingerol; H9c2 cells; CoCl2; p38/Nrf2/HO-1 pathway; pathway; p38/NF-KB pathway
Funding
- Foundation of Project of Science and Technology Research Project of Hebei Province [BJ2020002]
- Excellent Youth Program of Hebei University of Traditional Chinese Medicine [YQ2020003]
- Research Foundation of Administration of Traditional Chinese Medicine of Hebei Province [2022097]
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The study reveals that 6-gingerol can combat hypoxia-related oxidative stress by activating the Nrf2 pathway and inhibiting the p38/NF-kappa B pathway. The experiments demonstrate that 6-gingerol protects cardiomyocytes from hypoxia-induced damage and reduces oxidative stress and apoptosis.
Ginger, one of the most widely consumed condiment for various foods and beverages, has many pharmacological effects. 6-gingerol, a naturally occurring phenol, is one of the major pungent constituents of ginger. The purpose of this study was to characterize the effect of 6-gingerol on the p38/Nrf2/HO-1 and p38/NF-kappa B signaling pathway, as a possible means of combating hypoxia-related oxidative stress. H9c2 cells were chemically induced with CoCl2 to mimic hypoxia-associated cellular damage. Cardiomyocyte injury was assessed by lactate dehydrogenase and creatine kinase. Reactive oxygen species production was assessed by 2',7'-dichlorodihydrofluorescein diacetate. The antioxidative property of 6-gingerol was measured by estimating the activities of superoxide dismutase, catalase, glutathione and glutathione disulfide. Apoptosis was detected by flow cytometry after Annexin V-FITC-propidium iodide double staining. Western blotting was used to evaluate levels of p-p38, p38, cytoplasm p65, nuclear p65, total p65, nuclear Nrf2, total Nrf2, Keap1, HIF-1 alpha, and HO-1. 6-gingerol was able to counter hypoxia-induced cardiomyocyte injury as evidenced by inhibiting the levels of oxidative stress indexes and increasing the percentage of apoptosis. Furthermore, 6-gingerol was able to down-regulate p-p38/p38, nuclear p65, total p65 and Keap1 expression induced by CoCl2 stimulation and increased cytoplasm p65, nuclear Nrf2, total Nrf2, HO-1, and HIF-1 alpha expression. However, treatment with specific Nrf2 inhibitor blunted the activation of Nrf2 signaling and removed the protective effects of 6-gingerol. These experiments provide evidence that 6-gingerol exerts cytoprotective effects, which may be associated with the regulation of oxidative stress and apoptosis, potentially through activating the Nrf2 pathway and inhibiting the p38/NF-kappa B pathways.(C) 2022 Elsevier Inc. All rights reserved.
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