A Systems Pharmacology Approach to Determine Active Compounds and Action Mechanisms of Xipayi KuiJie’an enema for Treatment of Ulcerative colitis

Abstract

Abstract Xipayi Kui Jie’an (KJA), a type of traditional Uygur medicine (TUM), has shown promising therapeutic effects in Ulcerative colitis (UC). Owing to the complexity of TUM, the pharmacological mechanism of KJA remains vague. Therefore, the identification of complex molecular mechanisms is a major challenge and a new method is urgently needed to address this problem. In this study, we established a feasible pharmacological model based on systems pharmacology to identify potential compounds and targets. We also applied compound-target and target-diseases network analysis to evaluate the action mechanisms. According to the predicted results, 12 active compounds were selected and these compounds were also identified by HPLC-ESI-MS/MS analysis. The main components were tannins, this result is consistent with the prediction. The active compounds interacted with 22 targets. Two targets including PTGS2 and PPARG were demonstrated to be the main targets associated with UC. Systematic analysis of the constructed networks revealed that these targets were mainly involved in NF-κB signaling pathway. Furthermore, KJA could also regulate the CD4 + CD25 + Foxp3 + Treg cells. In conclusion, this systems pharmacology-based approach not only explained that KJA could alleviate the UC by regulating its candidate targets, but also gave new insights into the potential novel therapeutic strategies for UC.