Abstract
Background: Ulcerative colitis (UC), a chronic and challenging condition, necessitates the development of more effective treatments owing to the unsatisfactory efficacy and side effects associated with current medications. Traditional Chinese medicine (TCM), known for its multi-stage and multi-targeted approach, has a long history in treating gastrointestinal diseases and offering a promising alternative UC treatment. Panax ginseng (P. ginseng), a commonly used remedy for UC in TCM, exemplifies this potential, although the specific components and mechanisms through which its therapeutic effects are exerted remain to be fully elucidated, highlighting the need for further research to unlock its full potential as a treatment option. Aim: To investigate the key constituents and biological pathways through which P. ginseng exerts therapeutic effects on UC. Methods: Network pharmacology investigated the UC-alleviating mechanism of P. ginseng, including "active ingredient-target-disease" network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Panaxadiol (PD; active ingredient of P. ginseng) was tested in a mouse model of 3% dextran sulfate sodium-induced UC, with assessments of body weight, Disease Activity Index scores, and colon length. Colitis and intestinal barrier integrity were analyzed via hematoxylin-eosin and Alcian blue and periodic acid-Schiff staining, immunohistochemistry, real time-quantitative PCR, and western blotting. Results: By integrating and analyzing the targets of P. ginseng and UC, 15 critical hub genes were discovered. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the mechanisms involved to be linked to MAPK and PI3K-Akt signaling. Among the 10 main active ingredients identified as potentially effective, PD was most abundant and was validated in vivo to mitigate weight loss, reduce Disease Activity Index scores, and prevent colon shortening. PD also reduced inflammation and suppressed expression of pro-inflammatory cytokines and mediators. In addition, PD increased expression of mucin and tight junction proteins. Ultimately, PD counteracted effects of dextran sulfate sodium by inhibiting phosphorylation of NF-кB and MAPK, while increasing phosphorylation of AMPK and expression of NRF2 and NQO1. Conclusion: PD alleviates colitis and aids intestinal barrier repair, partly via modulation of the MAPK/NF-кB and AMPK/NRF2/NQO1 pathways. These findings also suggest new research methods for treatment of UC with TCM.