Fuzi-Baijiangcao Herb Pair Alleviates DSS-induced Ulcerative Colitis in Mice via Inhibiting the p38 MAPK/NF-κB/HIF-1α Signaling Pathway.

Background: Ulcerative colitis is an inflammatory intestinal tract disease that is complex and, difficult to heal, and prone to recurrence. The Fuzi-Baijiangcao (FB) herb pair is a commonly used drug combination for the clinical treatment of UC in China. However, its underlying mechanisms have not been elucidated. In this study, we explored the active ingredients of the FB herb pair and its potential mechanisms in the treatment of UC.

Methods: Firstly, the active ingredients and potential targets of Aconitum carmichaelii Debeaux (Fuzi) and Patrinia villosa (Thunb.) Juss (Baijiangcao) were obtained through network pharmacology. We identified differentially expressed genes (DEGs) in UC by bioinformatics analysis. Then, the common targets of the FB herb pair and UC were obtained, and the protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R language. The potential mechanism of the herb pair was validated through DSS induced UC mouse model.

Results: Thirty-four active ingredients corresponding to 546 potential targets were screened in the FB herb pair. Bioinformatics analysis revealed 2125 DEGs in UC. The GO and KEGG enrichment analyses showed that the FB herb pair was able to exert therapeutic effects by modulating multiple inflammatory pathways, including MAPK, HIF-1, and TNF. The results of animal experiments demonstrated that the FB herb pair could significantly downregulate the gene and protein expression of key molecules in the p38 MAPK/NF-κB/HIF-1α signaling pathway, thereby reducing the expression of pro-inflammatory factors and cell adhesion molecules, significantly improving the symptoms and intestinal pathology, and repairing the damage of the intestinal mucosa in the UC mice.

Conclusions: FB herb pair has Apparent therapeutic effects on UC, and its mechanisms may be related to the regulation of the p38 MAPK/NF-κB/HIF-1α signaling pathway to reduce the expression of inflammatory factors and repair intestinal mucosal damage.