Yuyang Decoction Regulates Macrophage Polarization and Repairs the Intestinal Mucosal Barrier via the TLRs/Tollip Signaling Pathway

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.