Picroside III, an Active Ingredient of Picrorhiza scrophulariiflora, Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity

Abstract

AbstractThis study aims to explore the protective effects of Picroside III, an active ingredient of Picrorhiza scrophulariiflora, on the intestinal epithelial barrier in tumor necrosis factor‐α (TNF‐α) induced Caco‐2 cells and dextran sulfate sodium (DSS) induced colitis in mice. Results show that Picroside III significantly alleviated clinical signs of colitis including body weight loss, disease activity index increase, colon shortening, and colon tissue damage. It also increased claudin‐3, ZO‐1 and occludin expressions and decreased claudin‐2 expression in the colon tissues of mice with colitis. In vitro, Picroside III also significantly promoted wound healing, decreased the permeability of cell monolayer, upregulated the expressions of claudin‐3, ZO‐1 and occludin and downregulated the expression of claudin‐2 in TNF‐α treated Caco‐2 cells. Mechanism studies show that Picroside III significantly promoted AMP‐activated protein kinase (AMPK) phosphorylation in vitro and in vivo, and blockade with AMPK could significantly attenuate the upregulation of Picroside III in ZO‐1 and occludin expressions and the downregulation of claudin‐2 expression in TNF‐α treated Caco‐2 cells. In conclusion, this study demonstrates that Picroside III attenuated DSS‐induced colitis by promoting colonic mucosal wound healing and epithelial barrier function recovery via the activation of AMPK.