Molecular Targets and Mechanisms of Scutellariae radix-Coptidis rhizoma Drug Pair for the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking.

Kai Niu,Bin Yu,Canlei Zheng,Lu’An Cui,Yi Qiao,Li Zhang,Qifang Li,Chao Wei,Kunrui Wang,Bing Sun,Bingbing Li,Honghua Zhang,Rong Wang,Yuan Liu,Dejan Stojkovic

doi:10.1155/2021/9929093

Abstract

This study aims to analyze the targets of the effective active ingredients of Scutellariae radix-Coptidis rhizoma drug pair (SCDP) in ulcerative colitis (UC) by network pharmacology and molecular docking and to explore the associated therapeutic mechanism. The effective active ingredients and targets of SCDP were determined from the TCMSP database, and the drug ingredient-target network was constructed using the Cytoscape software. The disease targets related to UC were searched in GeneCards, DisGeNET, OMIM, and DrugBank databases. Then, the drug ingredient and disease targets were intersected to construct a protein-protein interaction network through the STRING database. The Metascape database was used for the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the predicted targets of SCDP for UC. The Autodock software was used for molecular docking between the main active ingredient and the core target to evaluate the binding ability. SCDP has 43 effective active ingredients and 134 intersection targets. Core targets included AKT1, TP53, IL-6, VEGFA, CASP3, JUN, TNF, MYC, EGFR, and PTGS2. GO functional enrichment analysis showed that biological process was mainly associated with a cytokine-mediated signaling pathway, response to an inorganic substance, response to a toxic substance, response to lipopolysaccharide, reactive oxygen species metabolic process, positive regulation of cell death, apoptotic signaling pathway, and response to wounding. KEGG enrichment analysis showed main pathway concentrations were related to pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, bladder cancer, IL-17 signaling pathway, apoptosis, p53 signaling pathway, and PI3K-Akt signaling pathway. The drug active ingredient-core target-key pathway network contains 41 nodes and 108 edges, of which quercetin, wogonin, baicalein, acacetin, oroxylin A, and beta-sitosterol are important active ingredients; PTGS2, CASP3, TP53, IL-6, TNF, and AKT1 are important targets; and the pathways involved in UC treatment include pathways in cancer, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic, apoptosis, IL-17 signaling pathway and herpes simplex infection. The active ingredient has a good binding capacity to the core target. SCDP key active ingredients are mainly quercetin, wogonin, baicalein, acacetin, oroxylin A, and beta-sitosterol, which function mainly by regulating targets, such as PTGS2, CASP3, TP53, IL-6, TNF, and AKT1, and are associated with multiple signaling pathways as pathways in cancer, PI3K-Akt signaling pathway, apoptosis, IL-17 signaling pathways.

Highlights

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disease of the intestine characterized by abnormal intestinal mucosal structure, changes in intestinal bacterial composition, and systemic biochemical dysfunction
43 ingredients, including 32 in Scutellariae radix, 11 in Coptidis rhizoma, and coptisine and epiberberine as two common ingredients, were obtained (Table 1). en the target genes of 43 active ingredients were collected for target genes prediction in Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction
UC is a type of irritable bowel syndrome (IBS), and the main pathogenesis of UC is spleen deficiency as the original cause and damp-heat with stasis toxin as the superficial factors in traditional Chinese medicines (TCMs) theory [28,29,30]

Summary

Introduction

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disease of the intestine characterized by abnormal intestinal mucosal structure, changes in intestinal bacterial composition, and systemic biochemical dysfunction. It is an incurable disease with low mortality [1]. More and more patients eventually become refractory or intolerant to the side effects or complications of drugs, and the persistence of chronic inflammatory conditions often becomes a risk factor for inducing colorectal cancer [8, 9]. Much evidence has shown that TCM therapies, including Chinese herbal medicine, Chinese patent medicine, acupuncture, moxibustion, have potentially positive effects on UC [10, 11]

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Conclusion