Gingerenone A Alleviates Ferroptosis in Secondary Liver Injury in Colitis Mice via Activating Nrf2–Gpx4 Signaling Pathway

• Published in: Journal of agricultural and food chemistry 2022-10, Vol.70 (39), p.12525-12534
• Main Authors: Chen, Yonger, Zhu, Shumin, Chen, Zongwen, Liu, Ying, Pei, Chaoying, Huang, Haiyang, Hou, Shaozhen, Ning, Weimin, Liang, Jian
• Format: Article
• Language: English
• Subjects: Bioactive Constituents, Metabolites, and Functions
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.2c05262

Patients with ulcerative colitis (UC) have been found to be frequently associated with secondary liver injury (SLI). In this study, we investigated the protective effect of GA on dextran sodium sulfate (DSS)-induced SLI in mice and its mechanism. The SLI was established by adding 4% DSS in the drinking water of mice, and the effects of GA (5, 20 mg/kg, p.o., once a day for 7 days) in hepatic tissues were analyzed. HepG2 cells were induced by lipopolysaccharide (LPS) to detect the effect of GA on ferroptosis and the underlying mechanism. Pathological damage was determined by H&E. Liver parameters (AST and ALT), antioxidant enzyme activities (MDA and SOD), and the level of Fe2+ in the liver were detected by kits. Cytokine levels (TNF-α, IL-1β, and IL-6) and Gpx4 activity in the liver were detected by ELISA. Finally, the activation of nuclear factor erythroid 2-like 2 (Nrf2) was detected to explore the mechanism. The results indicated that GA significantly attenuated DSS-induced hepatic pathological damage, liver parameters, and cytokine levels and increased the antioxidant enzyme activities. Moreover, GA attenuated ferroptosis in DSS-induced liver injury and upregulated Gpx4 expression in DSS-induced mice. Mechanistic experiments revealed that GA activated Nrf2 in mice. Taken together, this study demonstrates that GA can alleviate ferroptosis in SLI in DSS-induced colitis mice, and its protective effects are associated with activating the Nrf2–Gpx4 signaling pathway.