Abstract
Background
Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease with a high recurrence rate. Given that no efficient treatment for UC is currently available, there is an urgent need for novel therapeutic strategies. Fuzi, as a traditional Chinese medicine, has anti-inflammatory and immunomodulatory properties. However, the bioactive compounds and mechanisms of fuzi in the treatment of UC are not completely understood.
Method
The active components of fuzi were retrieved from TCMSP; PharmMapper was used to predict the target of the active components of fuzi; UC-related disease targets were obtained from OMIM and Genecards databases, and Venny2.1 was used to intersect with fuzi to obtain common targets; KEGG and GO were performed on the common targets using R 4.0.2. String, Cytoscape3.9.0 was used to construct a protein interaction network for the intersection target. We then determined the role of the candidate molecule from fuzi, Higenamine (Hig), in a mouse model of DSS-induced colitis.
Result
Totally 21 active components and 420 corresponding targets of fuzi were obtained, of which 224 common targets were identified by intersecting with UC-related targets. The GO, KEGG, and PPI results suggested that fuzi and Hig may target AKT1 to regulate the PI3K/AKT pathway in UC. Animal experiments have shown that Hig treatment greatly reduced DSS-induced colitis, as measured by the DAI score, colonic inflammation, and intestinal barrier integrity. Mechanistically, Hig downregulated the DSS-induced PI3K-AKT signaling pathway by inhibiting AKT phosphorylation.
Conclusion
Fuzi may treat UC through multiple components, targets, and pathways. The active component Hig is likely to play a role in the treatment of UC. Hig alleviated DSS-induced colitis in mice, possibly by inhibiting colon inflammation, reducing colon neutrophilic infiltration, and improving the intestinal barrier by regulating the PI3K-AKT signaling pathway.