Abstract
Background: The purpose of the research is to identify the main active ingredients in Coptidis Rhizoma (CR) and explore the possible molecular mechanisms in the treatment of Kawasaki disease (KD).Materials and Methods: A total of 58 children with KD were randomly divided into a control group and a Berberine treatment group. The therapeutic indicators of the two groups before and after treatment were compared. Then, compounds and drug targets of CR from the TCMSP, SWISS, SEA, and the STITCH were collected, and targeted KD genes were retrieved from the DisGeNET, DrugBank, and GeneCards databases. The network pharmacology approach involved network construction, target prediction, and module analysis. GO and KEGG enrichment analysis were performed to investigate the possible pathways related to CR for KD treatments. Finally, protein expression was determined to verify the core targets using Western blotting in the cell experiment.Results: In total, nine compounds, 369 relative drug targets, and 624 KD target genes were collected in the above database. The network analysis revealed that 41 targets might be the therapeutic targets of CR on KD. GO and KEGG enrichment analysis revealed that the biological processes, namely, response to hormone, response to inorganic substance, and enzyme-linked receptor protein signaling pathway, and Pathways in cancer, Toll-like receptor signaling pathway, and Pancreatic cancer are the most significant. Protein expression of CASP3, PTGS2, and SRC was upregulated and AKT1 and ERK were downregulated.Conclusion: We provided useful resources to understand the molecular mechanism and the potential targets for novel therapy of KD.
Highlights
Kawasaki disease (KD) is a systemic inflammatory vasculitis predominantly affecting children younger than 5 years of age [1] and is the most common acquired heart disease among children in North America, Europe, and Japan [2]
KD can cause permanent vascular complications, especially coronary artery aneurysms (CAA) that may result in myocardial infarction [3, 4] and may Network Pharmacology Kawasaki Disease Mechanism be associated with serious cardiovascular sequelae in adulthood [5]
The BBR group was able to reduce the values of Creactive protein (CRP), neutrophils/lymphocytes (NLR), and platelets/lymphocytes (PLR), and there was no statistical divergence in the number of days with fever, WBC, PLT, AST, ALT, and other blood indexes between the samples
Summary
Kawasaki disease (KD) is a systemic inflammatory vasculitis predominantly affecting children younger than 5 years of age [1] and is the most common acquired heart disease among children in North America, Europe, and Japan [2]. KD can cause permanent vascular complications, especially coronary artery aneurysms (CAA) that may result in myocardial infarction [3, 4] and may Network Pharmacology Kawasaki Disease Mechanism be associated with serious cardiovascular sequelae in adulthood [5]. The standard treatment for KD includes intravenous gamma globulin (IVIG) and high-dose aspirin. Up to 15–20% of patients with KD do not respond to IVIG treatment and have an increased rate of CAA [6]. It is important to systematically elucidate the mechanism of the disease and search for more effective agents against it. The purpose of the research is to identify the main active ingredients in Coptidis Rhizoma (CR) and explore the possible molecular mechanisms in the treatment of Kawasaki disease (KD)
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