Corn Peptides Alleviate Nonalcoholic Fatty Liver Fibrosis in Mice by Inhibiting NLRP3 Inflammasome Activation and Regulating Gut Microbiota

This study aimed to investigate the effects of corn gluten-derived soluble epoxide hydrolase (sEH) inhibitory peptides on nonalcoholic fatty liver fibrosis induced by a high-fat diet and carbon tetrachloride in mice. Mice treated with corn peptides at doses of 500 or 1000 mg/kg/d for 4 weeks exhibited reduced sEH activity in serum and liver, enhanced lipid metabolism, and decreased lipid accumulation and oxidative stress. Corn peptides effectively downregulated the mRNA levels of <i>Pro-IL-1β</i>, <i>Pro-IL-18</i>, NOD-like receptor protein 3 (<i>NLRP3</i>), <i>ASC</i>, <i>Pro-caspase-1</i>, <i>Caspase-1</i>, and <i>GSDMD</i> in the liver. This hepatoprotective effect of corn peptides by inhibiting NLRP3 inflammasome activation was further validated in H₂O₂-induced HepG2 cells. Moreover, corn peptides restored the composition of the gut microbiota and promoted short-chain fatty acid production. This study provides evidence that corn-derived sEH inhibitory peptides have hepatoprotective activity against nonalcoholic fatty liver fibrosis by suppressing NLRP3 inflammasome activation and modulating gut microbiota.