[Methyl syringate alleviates DSS-induced colitis in mice by suppressing intestinal epithelial cell apoptosis via inhibiting the MAPK signaling pathway].

OBJECTIVES

To investigate the protective effect of methyl syringate (MS) against dextran sodium sulfate (DSS)‑induced colitis in mice and the underlying mechanism.

METHODS

Twenty-four C57BL/6 mice were random and equally into control group, DSS model group, and MS (100 mg/kg) treatment group. The therapeutic effect of MS on colitis was assessed by measuring changes in body weight, disease activity index (DAI) score and colon length and histopathological examinations with HE and AB-PAS staining. ELISA and RT-qPCR were used to detect the expressions of IL-6, TNF-α, and IL-10 in the colon tissue, and immunohistochemistry, immunofluorescence staining, Western blotting and TUNEL staining were used to detect the expressions of myeloperoxidase (MPO), tight junction proteins ZO-1 and claudin-1, and MAPK pathway proteins as well as cell apoptosis in the colon. In cultured NCM460 cells treated with 1% DSS, the effects of MS (50 μmol/L) treatment on cell apoptosis and expressions of poptosis-related proteins and MAPK pathway proteins were evaluated using flow cytometry and Western blotting.

RESULTS

MS treatment significantly ameliorated DSS-induced body weight loss, colon shortening, increased DAI score and histological inflammation score, and intestinal pathologies in mice. MS downregulated IL-6, TNF-α, and MPO, upregulated IL-10, and restored the expression and distribution of ZO-1 and claudin-1 in the colon tissue of the mice. In the mouse and cell models, MS treatment significantly reduced apoptosis rate of intestinal epithelial cells, upregulated Bcl-2 and XIAP, and downregulated cleaved caspase-3 expressions. KEGG enrichment analysis suggested a possible association of MAPK pathway with the therapeutic effect of MS, which was confirmed by lowered phosphorylation levels of p-JNK, p-ERK, and p-p38 in both the MS-treated mouse and cell models.

CONCLUSIONS

MS alleviates DSS-induced colitis in mice by reducing intestinal epithelial cell apoptosis and improving intestinal barrier damage possibly by inhibiting the MAPK signaling pathway.