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

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.

Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome

“…Network pharmacology is an excellent tool to construct a drug-target network and reveal the underlying mechanisms of TCM. Spleen deficiency was regarded as the original cause of UC based on TCM theory [ 27 ]. Additionally, spleen deficiency and liver stagnation are the root causes of IBS [ 28 , 29 ].…”

Artemisinin Alleviates Intestinal Inflammation and Metabolic Disturbance in Ulcerative Colitis Rats Induced by DSS

“…As a proinflammatory factor, IL-23 is involved in the formation and expansion of IL-17. When the IL-23/IL-17 inflammatory axis is formed, the inflammatory response continues to expand [ 29 ]. In addition, Peter et al found that the IL-33/ST2 axis can aggravate Dss-induced colitis and IL-33 can specifically induce the activation of key pathogenic cytokines including IL-17 and IL-13 and maintain and amplify the inflammatory response of the IL-17 signaling pathway [ 30 ].…”

Therapeutic targets and pharmacological mechanisms of Coptidis Rhizoma against ulcerative colitis: Findings of system pharmacology and bioinformatics analysis

“…Considering the adverse effects of first-line treatment, it is urgent to find safe and effective alternative medicines. Numerous studies have demonstrated that CR can ameliorate UC and its complications ( Niu et al, 2021 ; Xie et al, 2022 ; Yang Y et al, 2022 ). However, the therapeutic mechanism of CR exerted on UC has not been scientifically and systematically elucidated.…”

“…As a natural medicine, Coptidis Rhizoma (CR) has been used to alleviate the notable symptoms of UC for thousands of years in China, such as bloody diarrhea, tenesmus and abdominal pain ( Wang et al, 2020 ; Lu et al, 2021 ; Niu et al, 2021 ). Previous studies have demonstrated that CR has the pharmacological effects of anti-inflammatory, anti-bacterial, anti-oxidant, anti-tumor and other pharmacological effects ( Nagajyothi et al, 2014 ; Kwon et al, 2021 ; Kang et al, 2022 ).…”