Jie Lian, Guichun Jin, Jing Li, Weijuan Zhang, Yongtai Chang, Wenwu Li, Hua Zhi, Jiao Tian, Chen Liang, Juanping Su

Shanxi Traditional Chinese Medical Hospital, Taiyuan, People’s Republic of China

Correspondence: Juanping Su, Shanxi Traditional Chinese Medical Hospital, Taiyuan, People’s Republic of China, Email sjp2861@163.com

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation and impaired intestinal epithelial barrier. Current treatments have limitations, prompting interest in traditional Chinese medicine as potential alternatives. Yuyang Decoction (YYD) is a traditional formula with observed gastrointestinal protective effects, but its mechanisms remain unclear.
Objective: To evaluate the therapeutic effects and underlying mechanisms of YYD on intestinal mucosal barrier repair in a UC mouse model.
Methods: UC was induced in male C57/BL6 mice using 3% dextran sulfate sodium (DSS). Mice were randomly assigned to six groups: control, DSS model, low/medium/high-dose YYD, and mesalazine (positive control). Disease activity index (DAI), colon length, histopathology, cytokine levels, and tight junction protein expression were assessed. Tollip and IKK-β levels were detected by Western blot and immunofluorescence. Active components in YYD-containing serum were identified by UPLC-Q-Tof-MS/MS. In vitro, Tollip knockdown in THP-1 macrophages examined YYD’s effect on macrophage polarization and Caco-2 cell barrier integrity.
Results: YYD significantly reduced DAI scores, reversed colon shortening, and alleviated histological damage. Expression of tight junction proteins (occludin, claudins, ZO-1) and Tollip was upregulated. YYD-containing serum suppressed LPS-induced M1 macrophage polarization and protected epithelial tight junctions in vitro. These effects were diminished upon Tollip silencing.
Conclusion: YYD alleviates DSS-induced colitis by enhancing intestinal barrier repair and modulating immune responses. Its therapeutic effect may involve activation of the Tollip signaling pathway, which inhibits pro-inflammatory M1-like macrophage differentiation and reduces epithelial damage.

Keywords: Yuyang decoction, ulcerative colitis, occlusal protein, closure protein, TLRs/Tollip signaling pathway