基于网络药理学和分子动力学模拟分析柴胡疏肝散治疗甲状腺功能亢进症伴失眠作用机制OA

Objective:To analyze the action mechanism of Chaihu Shugan Powder in treating hyperthyroidism complicated by insomnia by integrating network pharmacology and molecular dynamics simulation.Methods:The main chemical components and their corresponding targets of Chaihu Shugan Powder were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Swiss Target Prediction platform.Disease-related targets for hyperthyroidism and insomnia were retrieved from multiple databases,and the intersection with the targets of Chaihu Shugan Powder was obtained.The STRING database was used to construct the protein-protein interaction(PPI)network of the intersecting targets.Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of the intersecting targets were performed via the Metascape platform.The top five core targets and core active components(ranked by degree value)were selected for molecular docking between ligands and receptors using Discovery Studio 2019 software,and the results were visualized.Gromacs 2022 was used for molecular dynamics simulation to evaluate the stability of interactions between core active components and key targets.Results:A total of 132 active components of Chaihu Shugan Powder were screened,corresponding to 883 targets,along with 1 331 targets related to hyperthyroidism and 2 361 targets related to insomnia.The intersecting targets between the drug and the diseases amounted to 62.The core components of Chaihu Shugan Powder for treating this disease included quercetin,isorhamnetin,naringenin,sitosterol,and licopyranocoumarin,etc.The core targets mainly included AKT serine/threonine-protein kinase 1(AKT1),interleukin(IL)-6,tumor necrosis factor(TNF),B-cell lymphoma-2(BCL2),and albumin(ALB).GO functional analysis showed that the biological processes were mainly enriched in responses to hormonal stimuli and other processes,the cellular components were concentrated in functional locations such as the membrane side,and the molecular functions involved signal receptor regulatory activity and other functions.KEGG pathway enrichment analysis mainly focused on signaling pathways including advanced glycation end-products and receptor for advanced glycation end products(AGE-RAGE),phosphatidylinositol 3-kinase-protein kinase B(PI3K-AKT),and Janus kinase-signal transducer and activator of transcription(JAK-STAT).Molecular docking results showed that core active components could bind well to key targets,and molecular dynamics simulation further verified the stability of the AKT1-quercetin and ALB-isorhamnetin complexes.Conclusion:Network pharmacology analysis suggests that Chaihu Shugan Powder exerts therapeutic effects on hyperthyroidism complicated by insomnia through components such as quercetin,isorhamnetin,naringenin,sitosterol,and licopyranocoumarin,acting on targets including AKT1,IL-6,TNF,BCL2,and ALB,and regulating signaling pathways such as AGE-RAGE,PI3K-AKT,and JAK-STAT.