Vincamine improves 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in mice through regulating TLR4/NF- κB signal

ObjectiveTo investigate the effect and possible mechanism of vincamine (VC) on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced Crohn's disease (CD)-like colitis in mice.

MethodsWild-type (WT) mice aged 6-8 weeks old (C57BL/6J, male) were randomly divided into control group (WT group), model group (TNBS group) and VC-treated group (VC group), with 8 mice in each group.VC group was treatment with VC (40 mg·kg^-1·d^-1, soluble in 1% Tween 80, gavage) after successful modeling, while WT group and TNBS group received the same amount of 1% Tween 80.The body weight changes, disease activity index(DAI) scores, colon lengths, histological scores and the level of inflammatory mediators in colon mucosa (TNF-α, IL-1β, IL-6) was used to evaluate the effect of VC on CD-like colitis in TNBS model mice.The potential target of VC acting on CD was predicted by SuperPred and DisGeNet database.The DAVID database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the results were visualized using the Cytoscape software.The combination of VC with PTGS3, NFKB1 and TLR4 were analyzed by the molecular docking technology and the effect of VC on TLR4/NF-κB signal were further verified by animal experiments.

ResultsThe weight loss, DAI scores and colonic shortening in the VC group were lower than that in the TNBS group(P < 0.05), but still higher than the WT group(P < 0.05);the histological scores in VC group was significantly lower than that in TNBS group(P < 0.05);inflammatory mediators(TNF-α、IL-1β、IL-6) level in colon mucosa of VC group were lower than those in TNBS group(P < 0.05), but still higher than those in WT group(P < 0.05).Network pharmacology and molecular docking showed that VC could regulate TLR4/NF-κB signal, and further Western blotting results showed that the level of TLR4 and p-p65 in colon mucosa of VC group were significantly lower than those in TNBS group(P < 0.05), but still higher than that in WT group(P < 0.05).

ConclusionsVC can improve TNBS-induced colitis in mice probably through inhibiting TLR4/NF-κB signal.