ABSTRACT
Objective::To explore the pharmacological mechanism of Xiao Xianxiongtang in treating type 2 diabetes mellitus (T2DM) by network pharmacology. Method::The main active ingredients, corresponding targets and target genes of Xiao Xianxiongtang were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) website. Relevant target genes of T2DM were obtained through Gene Cards. The targets of drug active ingredients were mapped to the targets of T2DM, and the intersection targets were obtained as the predictive targets of Xiao Xianxiongtang on T2DM. Cytoscape 3.7.1 software was used to construct the drug active ingredient-intersection target network model and select the key active ingredients. Interactive protein-protein interaction network (PPI) was constructed by STRING website, and key target genes were selected. Gene function analysis (GO) and enrichment analysis based on the Kyoto encyclopedia of genes and genomes (KEGG) pathway were performed on the intersecting targets using DAVID6.8 online tool. Result::Xiao Xianxiongtang had 30 active ingredients, 156 relevant targets, 14 key active ingredients and 18 key target genes on T2DM. GO analysis showed that the biological functions of Xiao Xianxiongtang in the treatment of potential genes of T2DM mainly involved transcriptional regulation, oxidative stress, protein binding and inflammatory reaction. KEGG pathway enrichment showed that the main pathways of Xiao Xianxiongtang in the treatment of T2DM were hypoxia inducible factor-1 (HIF-1) signaling pathway, tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway and thyroid hormone signaling pathway, phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hepatitis B, hepatitis C, tyrosine kinase receptor2(ErbB) signaling pathway, calcium signaling pathway and nuclear factor-kappa B (NF-κB) signaling pathway. Conclusion: Xiao Xianxiongtang is a multi-component, multi-target and multi-pathway process in the treatment of T2DM. It plays an important role in the treatment of T2DM by regulating transcription, oxidative stress, protein binding and inflammatory reaction. Conclusion::The mechanism of Xiao Xianxiongtang in treating T2DM may alleviate insulin resistance, increase insulin sensitivity and reduce blood sugar by inhibiting the secretion of inflammatory factors, participating in anti-inflammatory response, reducing oxidative stress, increasing intracellular calcium concentration, blocking glucagon signaling pathway and activating PI3K/Akt pathway.
ABSTRACT
Objective: To explore the mechanism of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes mellitus based on network pharmacology. Method: Major chemical constituents, corresponding targets and target genes of Dahuang Huanglian Xiexintang were obtained by Traditional Chinese Medicine Systems Pharmacology(TCMSP), and target genes of type 2 diabetes mellitus were obtained by GeneCards. The target genes of drug and disease were mapped to predict target genes of Dahuang Huanglian Xiexintang for type 2 diabetes mellitus. Cytoscape3.7.1 software was used to construct the compound-target network and protein-protein interaction network (PPI) of traditional Chinese medicine. Gene ontology (GO) analysis of potential genes and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes (KEGG) pathway were carried out using DAVID 6.8 online tool. Result: There were 17 active ingredients, 94 related targets, 17 key active ingredients and 16 key targets in Dahuang Huanglian Xiexintang on type 2 diabetes mellitus. GO analysis showed that the biological functions of potential genes of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes were mainly related to oxidative stress, apoptosis, protein binding, inflammatory reaction, et al. KEGG pathway enrichment results showed that the pathways of potential genes of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes mainly involved hypoxia inducible factor(HIF), tumor necrosis factor(TNF), phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt), nuclear transcription factor-кB(NF-кB), and vascular endothelial growth factor(VEGF) signaling pathways. Conclusion: Dahuang Huanglian Xiexintang is a complex process of multi-component, multi-target and multi-pathway in the treatment of type 2 diabetes mellitus. It plays an important role in the treatment of type 2 diabetes mellitus by participating in oxidative stress, apoptosis, protein binding and inflammatory reaction.
ABSTRACT
Objective: To study the potential therapeutic targets of modified Taohe Chengqitang for type 2 diabetes mellitus based on network pharmacology. Method: Based on TCMSP database and Uniprot database, the active constituents and target genes of flavored modified Taohe Chengqitang were screened.Target genes of type 2 diabetes were screened by gene cards database and OMIM database, and Cytoscape software was used to construct " active component-target" interaction network diagram.The active component targets and disease targets were uploaded to the STRING database, the protein interaction network map (PPI) was constructed, and the characteristic values were calculated, and core genes were screened by using R language.Finally, R language was used to analyze gene ontology (GO) enrichment and kyoto encyclopedia of genes and genome (KEGG) pathway enrichment of key targets. Result: The 155 active components and 106 effective targets of modified Taohe Chengqitangin the treatment of type 2 diabetes were predicted.Quercetin, kaempferol and isorhamnetin were the most effective components, while estrogen receptor alpha (ESR1), peroxidosomal hyperplasia activates receptor gamma (PPARG) and androgen receptor (AR) were the most effective components.Core genes in PPI network areepidermal growth factor receptor (EGFR)and ESR1, etc.GO enrichment analysis shows that it can affect gene transcription, nuclear receptor activity, hormone receptor binding, neurotransmitter, etc.Enrichment analysis of KEGG pathway showed that fluid shear stress and atherosclerosis pathways were the most significant pathways, followed by advanced glycation end products-receptor for AGE (AGE-RAGE) pathway. Conclusion: Predicted by the method of network pharmacology modified Taohe Chengqitang key targets for prevention and treatment of type 2 diabetes and related pathways, results suggest the recipe has multiple targets, multiple pathways, such as complex mechanism, not only show that modified Taohe Chengqitang has hypoglycemic effect, but it also has anti-inflammatory, improve insulin resistance, regulate lipid metabolism, and biological functions.