Potential mechanism of Lactiflorin in treating ulcerative colitis via modulation of the PI3K/AKT pathway: a study integrating network analysis, bioinformatics analysis, and experimental evidence.

内容摘要

This study is aimed at investigating the therapeutic effects and the relevant mechanisms of Lactiflorin in ulcerative colitis (UC) via a combination of various methodologies. The PI3K/AKT pathway identified through network pharmacology, and key pathways and therapeutic effects were validated by animal experiments, molecular docking, and molecular dynamics simulations. The experimental verification was performed using an acute colitis model induced by 2.5% dextran sulfate sodium. This study further explored whether the key bioactive components could improve intestinal barrier integrity and alleviate ulcerative colitis by inhibiting the PI3K/AKT signaling pathway. We performed hematoxylin and eosin staining, cytometric bead array, western blotting, and immunofluorescence. Network analysis identified 718 predicted drug targets, among which 264 were related to UC therapeutic targets. Animal experiments further confirmed the significant role of the key pathways and the effects of the pharmacological intervention. Molecular docking and dynamics simulations demonstrated Lactiflorin with a strong binding affinity to STAT3 (-&#x2009;11.24&#xa0;kcal/mol), AKT1 (-&#x2009;15.61&#xa0;kcal/mol), and PIK3R1 (-&#x2009;11.95&#xa0;kcal/mol). In vivo experiments, Lactiflorin improved the Disease Activity Index score and histopathological score in UC-modelled mice and suppressed the expression of pro-inflammatory cytokines including IL&#x2011;23, IL&#x2011;12p70, IL&#x2011;17A, and IL&#x2011;1&#x3b1;. Western blot and immunofluorescence results revealed that Lactiflorin inhibited the expression of AKT, STAT3, and PI3K proteins (P&#x2009;<&#x2009;0.01). These findings suggest that Lactiflorin exerts potential therapeutic effects against UC through PI3K/AKT pathway.