Uncovering bioactive compounds and potential mechanisms of Jieduan-Niwan Formula against liver failure

Abstract

Background Liver failure is considered as the inability of the liver to perform its normal synthetic and metabolic function. Our previous data showed that Jieduan-Niwan formula (JDNW) induced liver failure, while its underlying mechanism remains unknown. Methods In the present study, we performed a network pharmacology to analyze the bioactive ingredients and related targets. Compound and target data of JDNW formula were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and targets related to liver diseases were obtained from DisGeNET database. Information of protein protein interaction were retrieved from STRING database. Network construction and degree calculation were used Cytoscape software. Metascape web-server was used for GO and KEGG pathway enrichment. A microarray data series (GSE72081) was obtained from Gene Expression Omnibus database and analyzed using R project and Connectivity Map. Ledock was used for molecular docking. Results A total of 114 unduplicated active ingredients were identified after ADME screening. After construction of a target-liver disease network, 28 targets were identified for anti-liver failure effect. These targets were significantly enriched in fluid shear stress and atherosclerosis, pathways in cancer, IL-17 signaling pathway, HIF-1 signaling pathway, insulin resistance, toxoplasmosis, prostate cancer, microRNAs in cancer, NF-kappa B signaling pathway, Chemical carcinogenesis, VEGF signaling pathway and complement and coagulation cascades pathways. After analyzing a public microarray data of quercetin, we found biological action of some NFκB inhibitors was similar to quercetin. Molecular docking study showed that quercetin possessed a capability to bind on IKKβ and inhibited NFκB activation. Conclusions JDNW formula treated liver failure via multiple targets and multiple pathways, including NFκB signal. Quercetin was identified as a key bioactive ingredient of JDNW formula and its anti-liver failure effect may involve in NFκB inhibition.