Atractylenolide III Ameliorates Ulcerative Colitis By Targeting IL-17RA to Suppress Macrophage M1 Polarization.

Atractylenolide III (ATL III), an active component of Atractylodes macrocephala, demonstrates therapeutic potential against ulcerative colitis (UC). In this study, ATL III effectively ameliorated UC symptoms in dextran sulfate sodium-induced mice, as demonstrated through comprehensive phenotypic assessments. Transcriptome sequencing and subsequent validation assays, including molecular docking, molecular dynamics simulations, surface plasmon resonance, drug affinity-responsive target stability, and cellular thermal shift assay, identified IL-17RA as the primary molecular target of ATL III. The in vivo mechanism was further confirmed using the IL-17RA antagonist Brodalumab, while plasmid transfection experiments provided additional mechanistic insights into cellular models. These findings demonstrate that ATL III exerts its therapeutic effects on UC by directly targeting IL-17RA, thereby suppressing proinflammatory NF-κB and MAPK signaling pathways and attenuating macrophage M1 polarization, ultimately mitigates UC-associated symptoms and intestinal barrier damage.