摘要
Abstract
Objective:Xiaoer Zhili Syrup is a traditional Chinese medicine preparation used for the treatment of attention deficit hyperactivity disorder(ADHD);however,its underlying mechanisms remain unclear.This study aims to investigate the potential mechanisms of Xiaoer Zhili Syrup in treating ADHD using network pharmacology and molecular docking approaches.
Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Bioinformatics Analysis Tool for Molecular Mechanism(BATMAN)were used to predict the active compounds and potential targets of Xiaoer Zhili Syrup.ADHD-related genes were retrieved from Online Mendelian Inheritance in Man(OMIM)and Human Gene Database(GeneCards).The UniProt database was used for target annotation of drug-related targets and disease-associated genes.Cytoscape software was used to construct a drug-component-target(D-C-T)network.Protein-protein interaction(PPI)networks were generated using the String database.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of potential targets were performed using the Metascape database.Molecular docking was conducted to validate the interactions between key compounds and core targets identified from the network analysis.
Results:Based on TCMSP and BATMAN databases,network pharmacological analysis of 20 major chemical compounds in Xiaoer Zhili Syrup identified 446 potential targets.A total of 645 ADHD-related targets were obtained from the OMIM and GeneCards,with 160 overlapping targets identified between the drug-related and disease-related targets.PPI network analysis revealed that the core targets included glutamate ionotropic receptor N-methyl-D-aspartate type subunit 2A(GRIN2A),sodium voltage-gated channel alpha subunit 8(SCN8A),solute carrier family 6 member 3(SLC6A3),adrenoceptor alpha 2A(ADRA2A),ankyrin 3(ANK3),B-cell chronic lymphocytic leukemia/lymphoma 11B(BCL11B),calcium voltage-gated channel subunit alpha 1C(CACNA1C),chromodomain helicase DNA binding protein 8(CHD8),dopamine receptor D4(DRD4),5-hydroxytryptamine receptor 1B(HTR1B),neurexin 1(NRXN1),paired box 6(PAX6),SET domain containing 2(SETD2),sonic hedgehog signaling molecule(SHH),SIN3 transcription regulator family member A(SIN3A),SWI/SNF related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 2(SMARCA2),glutamate ionotropic receptor AMPA type subunit 1(GRIA1),guanine nucleotide binding protein beta subunit 1(GNB1),forkhead box P1(FOXP1).GO and KEGG enrichment analyses using Metascape showed that the therapeutic mechanisms of Xiaoer Zhili Syrup in the treatment of ADHD may involve multiple signaling pathways,including neuroactive ligand-receptor interaction,dopaminergic synapse,immunoglobulin superfamily cell adhesion molecules,Ras,cyclic guanosine monophosphate-protein kinase G(cGMP-PKG),cell cycle,and polycomb repressive complex,as well as metabolic pathways such as carbon metabolism,lysine degradation,and folate biosynthesis.Molecular docking analysis demonstrated that the binding energies of the major components to the target proteins were all<-5 kcal/mol(1 kcal/mol=4.184 kJ/mol),with L-tyrosine exhibiting the strongest binding affinity to GRIN2A(-7.1 kcal/mol).
Conclusion:Xiaoer Zhili Syrup may exert therapeutic effects on ADHD through the regulation of multiple neurotransmitter-related signaling pathways,reflecting the synergistic characteristics of traditional Chinese medicine involving multiple components,multiple targets,and multiple pathways.These findings provide a theoretical basis for further investigation into the molecular mechanisms underlying the therapeutic effects of Xiaoer Zhili Syrup in ADHD.关键词
注意缺陷多动障碍/小儿智力糖浆/神经递质/网络药理学/分子对接Key words
attention deficit hyperactivity disorder/Xiaoer Zhili Syrup/neurotransmitters/network pharmacology/molecular docking分类
医药卫生
