Exploration on the Molecular Mechanisms of Huanglian Jiedu Decoction in Treating Alzheimer's Disease Based on Network Pharmacology and Bioinformatics
Objective:A network pharmacology-based approach combined with bioinformatics was performed to determine the bioactives,key targets,and potential molecular mechanisms of Huanglian Jiedu Decoction(HLJDD)against Alzheimer's disease(AD).Methods:Bioactives and potential targets of HLJDD were retrieved from Traditional Chinese Medicine Systems Pharmacology Analysis Database(TCMSP)and The Encyclopedia of Traditional Chinese Medicine(ETCM).The differentially expressed genes of AD were obtained by gene chip analysis of GEO database,and the potential disease genes of AD were screened jointly with GeneCards,OMIM,PharmGkb,TTD,and DrugBank databases.The intersection of disease genes and active ingredient targets was taken,and the active ingredient-target relationship network was constructed using Cytoscape 3.9.1 software.Based on the STRING database,the protein-protein interaction(PPI)network was constructed,and the core targets were analyzed and screened out,and gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed.Results:A total of 64 bioactive ingredients of HLJDD,265 HLJDD-AD intersecting genes,10 major components,12 potential targets with key regulatory roles were screened,and 2 480 biological processes,94 cellular components,248 molecular functions were obtained from GO functional enrichment analysis,and 187 relevant signaling pathways were obtained from KEGG pathway enrichment analysis.HLJDD acted on core targets such as TP53,estrogen receptor 1(ESR1),mitogen-activated protein kinase(MAPK1),protein kinase B1(AKT1),interleukin(IL)6,FOS,tumor necrosis factor(TNF),and BCL2 through core bioactive ingredients such as quercetin,baicalein,β-sitosterol,stigmasterol,and kaempferol.lt could regulate signaling pathways such as lipid and atherosclerosis pathway,hepatitis B signaling pathway,Kaposi's sarcoma-associated herpesvirus infection,fluid shear stress and atherosclerosis,interleukin(IL)-17,and participates in biological processes such as exogenous stimulus response,membrane potential modulation,reactive oxygen species response,oxidative stress response,and lipopolysaccharide response to exert some role in the improvement of AD.Conclusion:HLJDD may act against AD through multi-bioactives,multi-targets,and multi-pathways.
万方数据
维普
