Abstract
Objective: To investigate the effects and mechanisms of esculin in protecting against palmitic acid-induced intestinal barrier disruption in mice. Methods: Thirty-two male BALB/c mice were randomly assigned to four groups: control, model, esculin, and esculin+ML385 groups. A model of intestinal barrier injury was induced by daily gavage of 10 mg/kg palmitic acid for 3 days in all groups except for the control group. The esculin group received 100 mg/kg esculin orally for the same duration, while the esculin+ML385 group was additionally treated with 30 mg/kg ML385 intraperitoneally before each gavage. Disease severity was assessed using the disease activity index (DAI). TNF-α, IL-1β, IL-6, MDA, and T-AOC levels were measured using biochemical assays. mRNA expression of inflammatory and protective markers was determined using qPCR, and the protein levels of occludin, ZO-1, Nrf2, and HO-1 were detected using Western blot. Results: The DAI was significantly lower in the esculin group compared to the model group (P < 0.001). Serum TNF-α, IL-6, and IL-1β levels were significantly reduced in the esculin group (P < 0.001), while T-AOC increased and MDA decreased (P < 0.001). Intestinal mucosa showed elevated levels of TNF-α, IL-1β, ZO-1, Nrf2, HO-1, and occludin in the esculin group (P < 0.05), while ML385 reversed these protective effects. Conclusion: Esculin alleviates palmitic acid-induced intestinal barrier damage by activating the Nrf2/HO-1 signaling pathway and inhibiting inflammation, indicating its potential therapeutic role in managing intestinal barrier dysfunction.