Phillygenin alleviated 2, 4, 6-trinitrobenzene sulfonic acid-induced Crohn's disease-like colitis by inhibiting IL-17 signaling

ObjectiveTo explore the effect and potential molecular mechanism of phillygenin (PHI) on Crohn's disease (CD) -like colitis induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS).

MethodsEighteen wild-type mice (C57BL/6J) aged 6-8 weeks were randomly divided into control group (WT group), model group (TNBS group) and PHI administration group (PHI group), with 6 mice in each group.Mice in the TNBS group and PHI group were treated with TNBS-induced CD colitis model while mice in the PHI group were given PHI administration (20 mg·kg^-1·d^-1, gavage) after modeling, while mice in the WT group and the TNBS group were given the same amount of 0.9% sodium chloride solution.After 7 days, the disease activity index (DAI), bodyweight changes and colon length were used to evaluate the symptoms of colitis.HE staining and histological inflammation scores were used to observe the injury degree of colon tissue.The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) in colonic mucosal tissues of mice were determined by enzyme-linked immunosorbent assay.Network pharmacology was used to predict the possible mechanism of PHI action on CD and further verified by Western blotting.

ResultsThe DAI scores and colon shortening in the PHI group were significantly lower than those in the TNBS group (P < 0.01), but still higher than those in the WT group (P < 0.01).The body mass of mice in the PHI group was higher than that in the TNBS group and lower than that in the WT group(P < 0.01).The scores of colon histology and the levels of inflammatory mediators (TNF-α, IL-6 and IFN-γ) in colonic mucosa in the PHI group were significantly lower than those in the TNBS group (P < 0.01), but still higher than those in the WT group (P < 0.01).Network pharmacology analysis identified a total of 63 potential targets of PHI on CD.Bioinformatics enrichment analysis showed that PHI was mainly involved in the regulation of inflammatory response, and might be related to interleukin-17(IL-17) signaling pathway.Finally, Western blotting showed that the expression levels of IL-17, interleukin-17RA and nuclear factor κB activator 1 in colonic mucosal tissue of mice in the PHI group were significantly lower than those in the TNBS group, but still higher than those in the WT group(P < 0.05 to P < 0.01).

ConclusionsPHI can improve TNBS-induced CD-like colitis in mice, which may be related to the inhibition effect of IL-17 signaling pathway.