基于网络药理学及分子对接探讨疏肝降脂片治疗乳腺癌相关血脂异常的作用机制  

Study on Action Mechanism of Shugan Jiangzhi Tablets for Breast Cancer-Related Dyslipidemia Based on Network Pharmacology and Molecular Docking

作　　者：孙杨[1] 丘嫦[1] 谢宛君 戴燕[1] SUN Yang;QIU Chang;XIE Wanjun;DAI Yan

机构地区：[1]广东省中医院,广东广州510120

出　　处：《新中医》2022年第18期113-120,共8页New Chinese Medicine

基　　金：广东省中医药局项目(20181137)。

摘　　要：目的:运用网络药理学及分子对接探讨疏肝降脂片治疗乳腺癌相关血脂异常的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)检索疏肝降脂片所含药物的有效成分及作用靶点,采用GeneCards、DRUGBANK数据库筛选疾病靶点,使用Cytoscape 3.7.2软件构建“药物-活性成分-靶点-疾病”网络,利用STRING平台构建核心靶点蛋白质-蛋白质相互作用(PPI)网络,在Metascape平台针对核心靶点蛋白开展基因本体(GO)功能与京都基因和基因组百科全书(KEGG)通路富集分析,用AutoDock Vina软件进行活性成分与核心靶点的分子对接。结果:筛选药物有效活性成分104个及其潜在靶点288个,乳腺癌靶点6 302个,血脂异常靶点1 852个。药物活性成分主要有槲皮素、山柰酚、木樨草素、柚皮素、异鼠李素、黄柏酮,核心靶点主要有丝氨酸/苏氨酸蛋白激酶1 (AKT1)、肿瘤坏死因子(TNF)、V-JUN肉瘤病毒17癌基因同源物(JUN)、信号传导转录激活因子3 (STAT3)、肿瘤蛋白P53 (TP53)、磷脂酰肌醇-3-激酶(PIK3CA)、白细胞介素-6 (IL-6)。GO功能富集分析涉及细胞外刺激反应、细胞对脂质和脂多糖的反应等生物过程,膜筏、囊腔、内质网腔等细胞组件,以及受体活性、氧化还原酶活性、转录因子结合等分子功能。KEGG通路富集分析主要涉及晚期糖基化产物(AGE)-晚期糖基化终末产物受体(RAGE)信号通路、缺氧诱导因子(HIF)-1信号通路和胰岛素抵抗等。分子对接验证了靶点与活性成分的良好结合活性。结论:疏肝降脂片主要活性成分槲皮素、山柰酚、木樨草素、柚皮素、异鼠李素与其关键靶点AKT1、TNF、JUN、STAT3的结合可能是发挥对乳腺癌相关血脂异常治疗作用的重要机制。Objective:To explore the action mechanism of Shugan Jiangzhi tablets for breast cancerrelated dyslipidemia by network pharmacology and molecular docking. Methods:Effective components and action targets of the medicines contained in Shugan Jiangzhi tablets were searched through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP);disease targets were screened by GeneCards and DRUGBANK databases;the“medicine-active component-target-disease”network was constructed with Cytoscape3.7.2 software;the protein-protein interaction(PPI) network of core targets was constructed by STRING platform;the enrichment analysis of Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway was performed on Metascape platform for core target proteins;AutoDock Vina software was used for molecular docking between active components and core targets. Results : A total of 104 active components and 288 potential targets of medicines,6 302 targets for breast cancer and 1 852 targets for dyslipidemia were screened. The main active components of medicines were quercetin,kaempferol,luteolin,naringenin,isorhamnetin and obakunone. The main core targets were serine/threonine protein kinase 1(AKT1),tumor necrosis factor(TNF),V-JUN sarcoma virus 17 oncogene homolog(JUN),signal transducer and activator of transcription 3(STAT3),tumor protein P53(TP53),phosphatidylinositol-3-kinase(PIK3CA) and interleukin-6(IL-6). GO enrichment analysis involved biological processes such as extracellular stimulation response,cell response to lipids and cell response to lipopolysaccharide, cell components such as membrane raft, cyst cavity and endoplasmic reticulum lumen,as well as molecular functions such as receptor activity,activity of oxidoreductase and transcription factor binding. KEGG pathway enrichment analysis mainly involved AGE-RAGE signaling pathway,HIF-1signaling pathway and insulin resistance,etc. Molecular docking verified the good binding activity between the active components of Shugan Jia

关 键 词：乳腺癌 血脂异常 疏肝降脂片 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]