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

Abstract

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.

• Authors: Yonger Chen, Shumin Zhu, Zongwen Chen, Ying Liu, Chaoying Pei, Haiyang Huang, Shaozhen Hou, Weimin Ning, Jian Liang
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 70 Issue 39 Pg. 12525-12534 (Oct 05 2022) ISSN: 1520-5118 [Electronic] United States
• PMID: 36135333 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Cytokines
• Diarylheptanoids
• Drinking Water
• Interleukin-6
• Lipopolysaccharides
• NF-E2-Related Factor 2
• Tumor Necrosis Factor-alpha
• gingerenone A
• Dextran Sulfate
• Superoxide Dismutase

Topics

• Animals
• Antioxidants (pharmacology)
• Colitis (chemically induced, drug therapy, genetics)
• Cytokines (metabolism)
• Dextran Sulfate (adverse effects)
• Diarylheptanoids
• Drinking Water
• Ferroptosis
• Interleukin-6 (pharmacology)
• Lipopolysaccharides (adverse effects)
• Liver (metabolism)
• Mice
• NF-E2-Related Factor 2 (genetics, metabolism)
• Signal Transduction
• Superoxide Dismutase (metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)