基于网络药理学及分子对接探讨关黄母颗粒治疗更年期抑郁症的作用机制  

Exploring the Mechanism of Guanhuangmu Granules in Treating Menopausal Depression Based on Network Pharmacology and Molecular Docking Technology

作　　者：张凌云[1] 彭秘 熊国营 ZHANG Lingyun;PENG Mi;XIONG Guoying(Nanchang First Hospital,Nanchang Jiangxi 330000,China;The 908th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army,Nanchang Jiangxi 330000,China.)

机构地区：[1]南昌市第一医院,江西南昌330000 [2]中国人民解放军联勤保障部队908医院,江西南昌330000

出　　处：《药品评价》2024年第5期553-559,共7页Drug Evaluation

基　　金：江西省中医药管理局科技计划项目(2022B1067)。

摘　　要：目的采用网络药理学和分子对接技术探讨关黄母颗粒治疗更年期抑郁症潜在作用机制。方法利用TCMSP、Swiss Target Prediction、Gene-Cards、DisGeNET数据库获得活性成分及疾病作用靶点,并通过STRING数据库、Cytoscape软件筛选核心靶点并构建蛋白互作(PPI)网络图、“药物-活性成分-靶点”图;运用DAVID数据库进行基因本体(GO)功能富集及基因组百科全书(KEGG)通路富集分析,并通过分子对接试验进行验证分析。结果共筛选到关黄母颗粒活性成分70个,对应靶点857个。经PPI网络分析筛选到51个核心靶点,其中排名靠前的靶点有肿瘤蛋白p53(TP53)、原癌基因酪氨酸蛋白激酶Src(SRC)、蛋白激酶B1(Akt1)、信号传导和转录激活蛋白3(STAT3)、表皮生长因子受体(EGFR)。共筛选出234个GO条目,富集到138条与药物治疗更年期抑郁症相关的通路。分子对接显示关黄母颗粒核心活性成分与核心靶点具有较高亲和力。结论关黄母颗粒可能通过山柰酚、槲皮素、豆甾醇、β-谷甾醇、汉黄芩素等活性成分作用于TP53、SRC、Akt1、STAT3、EGFR等核心靶点来调控内分泌抵抗、雌激素信号通路、TNF信号通路、PI3K-Akt信号通路等,从而协同发挥治疗更年期抑郁症的作用。Objective The objective of this study was to investigate the potential mechanism of action of guanhuangmu granules in the treatment of climacteric depression using network pharmacology and molecular docking techniques.Methods TCMSP,Swiss Target Prediction,Gene-Cards,and DisGeNET databases were utilized to identify active ingredients and disease targets.Core targets were selected through STRING database and Cytoscape software analysis,resulting in the construction of protein-protein interaction(PPI)network diagram and drug-active ingredient-target diagram.GO functional enrichment analysis was performed using DAVID database,followed by Genomic Encyclopedia(KEGG)pathway enrichment analysis.Molecular docking tests were conducted to validate the findings.Results A total of 857 targets corresponding to 70 active components present in guanhuangmu granules were identified.PPI network analysis revealed 51 core targets including tumor protein p53(TP53),proto-oncogene tyrosine protein kinase Src(SRC),protein kinase B1(Akt1),signaling and transcription-activating protein 3(STAT3),and epidermal growth factor receptor(EGFR).Additionally,a total of 234 GO entries related to drug treatment for climacteric depression were screened along with identification of 138 enriched pathways.Molecular docking demonstrated high affinity between core active components found in guanhuangmu granules and their respective core targets.Conclusion Through actions on core targets such as TP53,SRC,Akt1,STAT3,EGFR etc.,kaempferol,quercetin stigasterolβ-sitosterol baicalein present in guanhuangmu granules may regulate endocrine resistance as well as estrogen signaling pathway TNF signaling pathway PI3K-Akt signaling pathway thereby synergistically contributing towards the treatment for menopausal depression.

关 键 词：网络药理学 分子对接 关黄母颗粒 更年期抑郁症 

分 类 号：R285[医药卫生—中药学]