Paeoniflorin regulates macrophage polarization and protects the intestinal barrier through SOCS1/JAK1/STAT1 pathway in ulcerative colitis.

Ulcerative colitis (UC) is a chronic idiopathic intestinal inflammatory disease, and its onset is closely related to immune disorders and intestinal barrier defects. Paeoniflorin (PF) is a natural component with anti-inflammatory and immunomodulatory activities. This study aims to explore whether PF can alleviate UC by regulating macrophage polarization and protecting intestinal barrier homeostasis. The results demonstrated that PF significantly improved colitis in mice induced by DSS, manifested as a reduction in disease activity index score, alleviation of colonic edema, restoration of colonic length, inhibition of spleen enlargement, maintenance of intestinal tissue structure integrity, and protection of intestinal barrier function. In vitro, PF not only inhibited apoptosis following DSS-induced injury, but also upregulated the expression of tight junction protein ZO-1, mucin MUC2, and epithelial adhesion molecule E-cadherin. Moreover, PF could inhibit the polarization of RAW264.7 macrophages to the M1 phenotype and promote their transformation to the M2. Mechanism studies further revealed that PF could inhibit JAK1/STAT1 phosphorylation and upregulate SOCS1 protein expression. In conclusion, this study suggests that PF may exert therapeutic effects on UC by regulating macrophage polarization and enhancing intestinal barrier function through modulation of the JAK1/STAT1/SOCS1 pathway.