Paeoniflorin improves ulcerative colitis via regulation of PI3K­AKT based on network pharmacology analysis.

ABSTRACT

Paeoniflorin (PF) is the primary component derived from Paeonia lactiflora and white peony root and has been used widely for the treatment of ulcerative colitis (UC) in China. UC primarily manifests as a chronic inflammatory response in the intestine. In the present study, a network pharmacology approach was used to explore the specific effects and underlying mechanisms of action of PF in the treatment of UC. A research strategy based on network pharmacology, combining target prediction, network construction, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking simulation was used to predict the targets of PF. A total of 288 potential targets of PF and 599 UC-related targets were identified. A total of 60 therapeutic targets of PF against UC were identified. Of these, 20 core targets were obtained by protein-protein interaction network construction. GO and KEGG pathway analyses showed that PF alleviated UC through EGFR tyrosine kinase inhibitor resistance, the IL-17 signaling pathway, and the PI3K/AKT signaling pathway. Molecular docking simulation showed that AKT1 and EGFR had good binding energy with PF. Animal-based experiments revealed that the administration of PF ameliorated the colonic pathological damage in a dextran sulfate sodium-induced mouse model, resulting in lower levels of proinflammatory cytokines including IL-1ß, IL-6, and TNF-α, and higher levels of IL-10 and TGF-ß. PF decreased the mRNA and protein expression levels of AKT1, EGFR, mTOR, and PI3K. These findings suggested that PF plays a therapeutic protective role in the treatment of UC by regulating the PI3K/AKT signaling pathway.