6-Gingerol exerts a protective effect against hypoxic injury through the p38/Nrf2/HO-1 and p38/NF-κB pathway in H9c2 cells.

Abstract

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-κB 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-1α, 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-1α 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-κB pathways.

• Authors: Xue Han, Panpan Liu, Bin Zheng, Muqing Zhang, Yuanyuan Zhang, Yucong Xue, Chenxu Liu, Xi Chu, Xiangting Wang, Shijiang Sun, Li Chu
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 104 Pg. 108975 (06 2022) ISSN: 1873-4847 [Electronic] United States
• PMID: 35245652 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Catechols
• Fatty Alcohols
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• NF-kappa B
• Reactive Oxygen Species
• gingerol
• Heme Oxygenase-1

Topics

• Catechols
• Fatty Alcohols
• Heme Oxygenase-1 (metabolism)
• Humans
• Hypoxia
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress
• Reactive Oxygen Species (metabolism)