Corn Peptides Alleviate\nNonalcoholic Fatty Liver Fibrosis\nin Mice by Inhibiting NLRP3 Inflammasome Activation and Regulating\nGut Microbiota

This study aimed to investigate the effects of corn gluten-derived\nsoluble epoxide hydrolase (sEH) inhibitory peptides on nonalcoholic\nfatty liver fibrosis induced by a high-fat diet and carbon tetrachloride\nin mice. Mice treated with corn peptides at doses of 500 or 1000 mg/kg/d\nfor 4 weeks exhibited reduced sEH activity in serum and liver, enhanced\nlipid metabolism, and decreased lipid accumulation and oxidative stress.\nCorn peptides effectively downregulated the mRNA levels of <i>Pro-IL-1β</i>, <i>Pro-IL-18</i>, NOD-like receptor\nprotein 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\nNLRP3 inflammasome activation was further validated in H<sub>2</sub>O<sub>2</sub>-induced HepG2 cells. Moreover, corn peptides restored\nthe composition of the gut microbiota and promoted short-chain fatty\nacid production. This study provides evidence that corn-derived sEH\ninhibitory peptides have hepatoprotective activity against nonalcoholic\nfatty liver fibrosis by suppressing NLRP3 inflammasome activation\nand modulating gut microbiota.