Dioscin ameliorates inflammatory bowel disease by up-regulating miR-125a-5p to regulate macrophage polarization.

Abstract

PurposeDioscin has been proven to have anti‐cancer, anti‐inflammatory, and anti‐infection roles. However, the role of Dioscin in inflammatory bowel disease (IBD) and its related mechanisms is unclear and needs further study.MethodsThe colitis model in mice was established. After Dioscin (20, 40, or 80 mg/kg) treatment, the colon length was measured by a ruler. Histopathology, inflammatory cytokines, gut permeability, tight junction proteins, macrophage infiltration, macrophage polarization, and miR‐125a‐5p level were detected by hematoxylin–eosin staining, enzyme‐linked immunosorbent assay, quantitative real‐time polymerase chain reaction (qRT‐PCR), FITC‐dextran, Western blot, and flow cytometry. In vitro experiments, after RAW264.7 cells induced by lipopolysaccharide (LPS)/interleukin‐4 (IL‐4), were treated with Dioscin and miR‐125a‐5p inhibitor, miR‐125a‐5p level, cell vitality, inflammatory cytokines, and M1/M2 marker genes were measured by qRT‐PCR and MTT assay.ResultsDioscin (20, 40, or 80 mg/kg) relieved DSS‐triggered colitis and restrained the serum and colon of pro‐inflammatory cytokines expression. Meanwhile, different concentrations' Dioscin weakened M1 macrophage polarization but facilitated tight junction protein expressions, M2 macrophage polarization, and miR‐125a‐5p level in colitic mice. Moreover, miR‐125a‐5p inhibitor reversed the modulation of Dioscin on miR‐125a‐5p expression, cell vitality, and inflammatory cytokines in lipopolysaccharide (LPS)‐induced RAW264.7 cells. We further discovered that Dioscin restrained M1 marker gene (CD16) expression while intensifying M2 marker genes (CD206 and Arginase‐1) expressions in vitro, which was reversed by miR‐125a‐5p inhibitor.ConclusionDioscin modulated macrophage polarization by increasing miR‐125a‐5p, thereby improving the intestinal epithelial barrier function and reducing IBD.