Osbeckia opipara attenuates inflammation and reconstructs the intestinal barrier in ulcerative colitis by modulating the AHR/IL-22/STAT3 signaling axis.

BACKGROUND

Ulcerative colitis (UC) poses a therapeutic challenge due to persistent epithelial barrier dysfunction. The traditional Miao medicine Osbeckia opipara (O. opipara) shows clinical efficacy, yet its mechanism remains unclear.

PURPOSE: To elucidate the therapeutic mechanism of O. opipara in UC through integrated pharmacological and experimental approaches.

STUDY

DESIGN

A bedside to bench translational framework was employed combining multiomics analysis, genetic causal inference, molecular simulation and experimental validation in preclinical models.

METHODS

Active constituents were characterized using ultra high performance liquid chromatography tandem mass spectrometry. Drug target Mendelian randomization (DTMR) identified aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 3 (STAT3) as pivotal genetic targets. Molecular dynamics simulations assessed ligand receptor interactions. Efficacy was evaluated in dextran sulfate sodium (DSS) induced colitis mice and lipopolysaccharide stimulated intestinal epithelial cells. Alterations in gut microbiota and host transcriptome were profiled by 16S ribosomal RNA sequencing and RNA sequencing respectively.

RESULTS

O. opipara alleviated DSS-induced colitis, at least in part, through modulation of the AHR/IL-22/STAT3 signaling axis in preclinical models. Gallic acid and Ellagic acid were identified as core AHR agonists. Treatment significantly suppressed inflammatory responses, restored gut microbiota homeostasis, and reconstructed intestinal barrier integrity by upregulating tight junction proteins. AHR inhibition abolished these therapeutic effects, confirming the mechanism's dependence on AHR activation.

CONCLUSION

O. opipara acts as a natural AHR agonist that modulates inflammation, microbiota dysbiosis, and barrier dysfunction to promote mucosal healing in preclinical UC models, providing mechanistic evidence supporting its traditional therapeutic application.