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, hub targets, and critical inflammatory signaling pathways (NFκB and STAT3) to be significantly attenuated by A. annua. Furthermore, A.annua improved transcellular and paracellular epithelial permeabilities by reducing intraepithelial bacteria, enhancing TEER, and decreasing FITC-dextran permeability. 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.