Dihydroartemisinin Alleviates Ulcerative Colitis via Target Identification and Pathway Modulation: A...

Ulcerative colitis (UC) is a long-term inflammatory condition impacting the bowel with an unclear cause. It is categorized as a refractory condition due to the limited efficacy and adverse effects of existing treatments. Dihydroartemisinin (DHA), a semi-synthetic derivative and primary active metabolite of artemisinin, exhibits anti-inflammatory and antioxidant properties. To assess the therapeutic effects of DHA on UC and elucidate its possible mechanisms of action. A dextran sulfate sodium (DSS)-induced UC mouse model (2.5% DSS for 30 days) was used to evaluate the therapeutic effects of DHA (20 mg/kg/day) through assessment of disease activity, colon damage, and inflammation. Key targets were identified using network pharmacology, followed by pathway analysis (GO and Kyoto Encyclopedia of Genes and Genomes [KEGG]), molecular docking, and western blotting to validate interactions and signaling modulation. DHA treatment significantly improved disease activity index (DAI) scores, reduced colon shortening, and ameliorated histopathological injury in the DSS-induced UC mouse model. Seven core targets of DHA were identified: EGFR, MMP9, PTGS2, MMP2, mitogen-activated protein kinase 3 (MAPK3), MAPK1, and ERBB2. Enrichment analyses revealed critical mechanisms and pathways implicated in its therapeutic effects. Molecular docking demonstrated robust binding between DHA and its targets, whereas western blot analysis confirmed that DHA mitigated UC via modulation of the MAPK inflammatory signaling pathway. The research highlights DHA's therapeutic potential in UC treatment by identifying its core targets and mechanisms of action, paving the way for future research and drug development in managing UC.