[1,3-dicaffeoylquinic acid mitigates dextran sulfate sodium-induced colitis in mice by alleviating oxidative stress via inhibiting the PI3K/Akt pathway].

OBJECTIVES

To investigate the protective effect of 1,3-dicaffeoylquinic acid (1,3-DA) against dextran sulfate sodium (DSS)-induced colitis in mice and its molecular mechanism.

METHODS

Fifty C57BL/6 mice were randomly divided into normal control group, DSS model group, 1,3-DA treatment group, PI3K inhibitor (LY294002), and 5-aminosalicylic acid (5-ASA; positive control) group. Except for those in the control group, the mice were given DSS to induce colitis and treated with daily intraperitoneal injections the indicated agents during modeling for 7 consecutive days. Colonic pathological phenotypes, inflammation, oxidative stress, and expressions of tight junction proteins and PI3K/Akt pathway proteins in the colon tissues of the mice were detected. In cultured intestinal epithelial NCM460 cells with H₂O₂-induced oxidative stress, the effects of 1,3-DA and 1,3-DA plus 740Y-P (a PI3K activator) were examined on intracellular oxidative stress and expressions of tight junction proteins.

RESULTS

Treatment of the mice with 1,3-DA significantly alleviated DSS-induced body weight loss, colon shortening, elevation of disease activity index and mucosal injury, downregulated interferon‑γ and myeloperoxidase, upregulated superoxide dismutase, catalase and glutathione peroxidase, reduced malondialdehyde, increased zonula occludens-1 and claudin-1, and inhibited overexpressions of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt). In NCM460 cells, treatment with 1,3-DA significantly reduced H₂O₂-induced reactive oxygen species accumulation, increased zonula occludens-1 and claudin-1 expressions, and lowered p-PI3K and p-Akt expression. The protective effects of 1,3-DA was obviously attenuated by treatment with 740Y-P.

CONCLUSIONS

1,3-DA ameliorates DSS-induced colitis in mice and H₂O₂-mediated intestinal epithelial injury by inhibiting inflammation and oxidative stress and promoting repair of intestinal barrier function, which is closely related to inhibition of excessive PI3K/Akt pathway activation.