Previously, peptide Asn-Cys-Trp (NCW), derived from Mizuhopecten yessoensis, was observed to up-regulate the mRNA expression of tight junction protein ZO-1 during its transport across a Caco-2 cell monolayer. Based on this, we hypothesized that NCW could protect tight junction integrity and thereby improve intestinal barrier function. This study aimed to investigate the protective effects of NCW against LPS-induced intestinal barrier dysfunction using both in vivo and in vitro models. In lipopolysaccharide (LPS)-stimulated Caco-2 monolayer cells, NCW was found to preserve barrier function, as evidenced by attenuated decline in transepithelial electrical resistance, attenuated reductions in Claudin-1, Occludin, and ZO-1 expression, and reduced secretion of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). In mice, oral administration of peptide NCW mitigated LPS-induced systemic and intestinal damage, as demonstrated by a lowered disease activity index and serum diamine oxidase level, alleviated jejunal and colonic histopathological damage and inflammation, and enhanced antioxidant capacity through increased colonic superoxide dismutase activity, coupled with suppressed jejunal malondialdehyde formation. Mechanistically, NCW may exert its protective effects by activating AMPK and inhibiting AKT. In conclusion, dietary peptide NCW could alleviate LPS-induced intestinal barrier injury. These findings provide novel insights into the potential application of food-derived peptides in promoting intestinal health.
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