摘要
目的 通过网络药理学和分子对接技术研究甘松-大黄-藿香配伍治疗肾透明细胞癌(KIRC)的作用机制。方法 在中药系统药理学数据库与分析平台(TCMSP)中,搜索甘松-大黄-藿香的主要活性成分和有效靶点。在GEO数据库中寻找KIRC的疾病效应靶点,建立甘松-大黄-藿香—生物活性成分—靶点网。取药物靶点和疾病靶点之间的交集,并使用STRING数据库构建蛋白质的相互作用网络,以研究蛋白质-蛋白质相关作用(PPI)之间的关联。对核心靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。对主要的生物活性组分和核心蛋白进行分子对接,以判断其结合能力。结果 甘松-大黄-藿香含有186个靶点,其与KIRC疾病靶点有96个交集靶点。通过药物—活性成分—靶点网络推测甘松-大黄-藿香治疗KIRC的关键成分有槲皮素、葛花苷元、芦荟大黄素和β-谷甾醇等,PPI网络中核心靶点为TP53、CASP3、MYC、EGFR、STAT1、Bax。GO富集分析结果发现,甘松-大黄-藿香治疗KIRC的靶点在生物过程主要包括对蛋白质结合的调节、对酶结合的反应等。KEGG结果显示,甘松-大黄-藿香通过肿瘤相关信号通路和PI3K-Akt信号通路等发挥抗KIRC作用。分子对接结果显示,甘松-大黄-藿香有效成分与其治疗KIRC的核心靶点均有较好的结合活性。其中β-谷甾醇与多个核心靶点均具有较高的结合能,与Bax的结合能高达-6.28 kcal·mol^(-1)。结论 甘松-大黄-藿香可通过β-谷甾醇等主要活性成分作用于TP53、CASP3、MYC、EGFR等靶点,参与PI3KAkt等信号通路有效治疗KIRC。
Objective To investigate the mechanism of action of Gan Song-Rhubarb-Patchouli combination in the treatment of clear cell carcinoma of kidney(KIRC)by network pharmacology and molecular docking technique.Methods In the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform(TCMSP),we searched for the main active ingredients and effective targets of Gan Song-Rhubarb-Patchouli.The disease effect targets of KIRC were searched in the GEO database to establish the Gan Song-Rhubarb-Patchouli-bioactive ingredient-target network.Intersections between drug targets and disease targets were taken and protein interaction networks were constructed using the STRING database to investigate protein-protein interaction(PPI)associations.The core targets were analyzed by gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment.Molecular docking of major bioactive components and core proteins were performed to determine their binding ability.Results There were 186 target points in Gan Song-Rhubarb-Patchouli.There were 96 overlapping targets with KIRC disease targets.Based on the drug-active ingredient-target network,it was estimated that the key components of the treatment of KIRC included quercetin,puerarin,aloe emodin andβ-sitosterol,etc.The core targets of the PPI network were TP53,CASP3,MYC,EGFR,STAT1 and Bax.GO analysis revealed that the targets of Gansong-Rhubarb-Patchouli in the treatment of KIRC mainly included the regulation of protein binding and the response to enzyme binding,etc.KEGG results showed that Gan Song-Rhubarb-Patchouli exerted its anti-KIRC effect through pathways in cancer,PI3K-Akt signaling pathway,etc.The molecular docking results showed that the core targets of Gan Song-Rhubarb-Patchouli and its core targets for the treatment of KIRC had better binding activities,the binding energy with Bax was-6.28 kcal·mol^(-1).Conclusion Gan Song-Rhubarb-Patchouli could act on the targets of TP53,CASP3,MYC,and EGFR through the main active ingredients such asβ-sitosterol,
作者
姜文婕
李佳庆
牛阳
南一
袁玲
窦红莉
JIANG Wenjie;LI Jiaqing;NIU Yang;NAN Yi;YUAN Ling;DOU Hongli(Ningxia Hui Autonomous Region Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of High Incidence,Yinchuan 750004,China;Ningxia Medical University,Yinchuan 750004,China;School of Pharmacy,Ningxia Medical University,Yinchuan 750004,China;School of Marxism,Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,China)
出处
《宁夏医科大学学报》
2024年第4期413-421,共9页
Journal of Ningxia Medical University
基金
宁夏医科大学科学研究基金资助项目(2001230501)。
关键词
肾透明细胞癌
甘松-大黄-藿香
网络药理学
分子对接
clear cell carcinoma of kidney
Gan Song-Rhubarb-Patchouli
network pharmacology
molecular docking
