Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited therapeutic options and notable side effects. Changyanqing (CYQHJ) Decoction, a traditional Chinese medicine formula, has shown therapeutic potential; however, its underlying mechanisms remain unclear. Objectives: This study aimed to elucidate the pharmacological mechanisms of CYQHJ in UC, with a focus on identifying key bioactive compounds and signaling pathways. Methods: Network pharmacology was leveraged to pinpoint potential targets, bioactive compounds and signaling pathways underlying CYQHJ’s therapeutic effects. Protein–protein interaction and KEGG enrichment analyses highlighted PI3K-Akt as a central pathway. In-vitro assays using Caco-2 cells validated the protective and anti-inflammatory effects of quercetin, the major active compound, in a DSS-induced injury model. Cell viability (CCK-8), cytokines (ELISA) and pathway protein expression (Western blot) were evaluated. Results: Quercetin was identified as a key compound targeting PI3K-Akt signaling. It significantly improved cell viability and reduced TNF-? and IL-6 levels (P<0.001). Western blot confirmed quercetin inhibited PI3K and Akt phosphorylation, while the PI3K-Akt activator Recilisib reversed these effects (P<0.001). Conclusion: CYQHJ exerts anti-inflammatory effects against UC mainly through PI3K-Akt inhibition, with quercetin as the core bioactive compound, providing mechanistic insight into its therapeutic action.