Objective To investigate the therapeutic effect of pedunculoside (PE) on dextran sulfate sodium salt (DSS)-induced ulcerative colitis (UC) and elucidate its molecular mechanism through in vitro and in vivo models. Methods DSS was used to establish a mouse UC model, combined with transcriptome analysis, the effect of PE on changes in body weight, colon length, colon tissue pathology, pro-inflammatory cytokine levels in colon tissue, and expressions of tight junction proteins (Occludin, E-cadherin, Claudin-1) were evaluated. Caco-2 monolayer cell model was established, the cell permeability was detected using fluorescein isothiocyanate-glucan (FITC-glucan) to evaluate the effect of PE on intestinal mucosal barrier function. Further validation of the regulatory effect of PE on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, inflammatory factors, and tight junction protein expression and distribution was achieved through molecular biology experiments such as Western blotting and ELISA. Results The results of in vivo experiments showed that PE could significantly reduce the disease activity index (DAI) score of mice (P < 0.001), alleviate pathological damage to colon tissue, reduce pro-inflammatory cytokine levels (P < 0.05, 0.001), and upregulate the expressions of tight junction proteins in colon tissue (P < 0.001). Transcriptome sequencing revealed that PE had a significant inhibitory effect on the overactivated PI3K/Akt signaling pathway in colon tissue of UC mice (P < 0.001). In vitro experimental results showed that PE could significantly reduce the permeability of Caco-2 monolayer cells (P < 0.001), inhibit the phosphorylation of Akt and PI3K in DSS-induced Caco-2 cell model (P < 0.01, 0.001), reduce the levels of inflammatory factors (P < 0.01, 0.001), and upregulate the expressions of Occludin, E-cadherin and Claudin-1 (P < 0.001). Conclusion PE could downregulate inflammatory response and enhance intestinal epithelial barrier function by inhibiting PI3K/Akt signaling pathway in both in vivo and in vitro models, thereby exerting a protective effect on DSS-induced UC.

ulcerative colitis  /  pedunculoside  /  transcriptome  /  PI3K/Akt signaling pathway  /  intestinal mucosal basal barrier  /  inflammatory factors