Elucidating the Potential Mechanism of Ulcerative Colitis Amelioration by Artemisia annua L. Based on Network Pharmacology and Experimental Validation.

BACKGROUND

Ulcerative colitis (UC) is a chronic and recurrent enteritis requiring comprehensive treatment. Artemisia annua L. (A. annua) has shown a promising role in UC therapy, yet its key components and mechanisms of action are not fully understood.

OBJECTIVE

This study aimed to investigate the effects of A. annua on UC, identify bioactive components, and elucidate underlying targets and mechanisms.

MATERIALS AND

METHODS

Candidate targets of A. annua components and UC targets were overlapped using the PPI network and GO and KEGG pathway enrichment analyses. Molecular docking, a DSS mouse model (BALB/c), and an LPS/IFNγ cell model were employed to validate the efficacy and mechanism of action of A. annua against UC.

RESULTS

The A. annua-ingredient-target-UC network included 21 active components, 65 candidate targets, and 10 hub genes. Molecular docking showed excellent fitting of the top 9 active components in the binding pocket of the top 6 hub targets. A DSS mouse model and an LPS/IFNγ cell model revealed the weight loss, intestinal inflammation, the expressions of hub targets and critical inflammatory signaling pathways molecules (p-NFκB and p-STAT3) to be significantly attenuated by A. annua. Furthermore, A.annua significantly reduced intraepithelial bacteria, enhanced TEER, and decreased FITC-dextran permeability in animal and cellular experiments.

CONCLUSION

This study demonstrated the significant protective effects of A. annua against inflammation and its ability to preserve the integrity of the transcellular and paracellular intestinal epithelial barrier, suggesting a promising application of A. annua in UC prevention and therapy.