摘要
目的:通过网络药理学和分子对接技术,探讨沙棘抗肥胖的活性成分、靶点和作用机制,并验证其体外抗肥胖效果。方法:使用TCMSP平台检索沙棘活性成分与靶点,收集疾病靶点,利用Venny 2.0.2得沙棘靶点与肥胖靶点的交集。通过STRING数据库平台建立药物靶点-疾病靶蛋白相互作用(PPI)网络。使用David数据库对交集靶点进行分析,得到GO富集分析和KEGG通路分析结果。通过Cytoscape 3.9.1软件构建沙棘成分-靶点-信号通路网络图。使用Autodock Dock 1.5.7和Pymol 2.2.0进行沙棘核心靶点与其成分的分子对接,并进行可视化处理。通过体外实验验证沙棘提取物的抗肥胖作用。结果:筛选得到33个沙棘活性成分,2820个疾病靶点和151个交集靶点。主要活性成分包括黄酮类、维生素类、甾醇类等,关键靶点涉及AKT1、TNF、IL6、TP53、VEGFA、CASP3等。KEGG通路富集分析得到恶性肿瘤通路、脂质与动脉粥样硬化通路、AGE-RAGE信号通路等131条信号通路。分子对接结果表明核心靶点与其对应活性成分对接结果良好。体外实验表明沙棘提取物具有抑制3T3-L1小鼠前脂肪细胞增殖的作用。结论:研究显示沙棘具有多成分、多靶点、多通路协同发挥抗肥胖作用,为其临床研究和产品开发提供了参考。
Objective:To investigate the active components,protein targets,and mechanisms underlying the anti-obesity effects of Hippophae fructus using network pharmacology and molecular docking techniques,and to validate its in vitro anti-obesity efficacy.Methods:The TCMSP platform was utilized to retrieve the active components and targets of Hippophae fructus,and disease targets were collected.Venny 2.0.2 was used to identify the intersection of targets between Hippophae fructus and obesity-related targets.The STRING database was used to establish a drug-target-disease protein interaction(PPI)network.The intersecting targets were analyzed using the David database to perform GO enrichment analysis and KEGG pathway analysis.Cytoscape 3.9.1 was used to construct a network diagram of the components of Hippophae fructus,anti-obesity targets,and related signaling pathways.Autodock Dock 1.5.7 and Pymol 2.2.0 were used to carry out molecular docking between the core targets of Hippophae fructus and its components,followed by visualization.The in vitro anti-obesity effect of Hippophae fructus extract was evaluated through cell experiments using 3T3-L1 cells.Results:A total of 33 active components,2820 disease targets,and 151 intersection targets of Hippophae fructus were identified.The main active components included flavonoids,vitamins,and sterols,while key targets involved AKT1,TNF,IL6,TP53,VEGFA,CASP3,and others.KEGG pathway enrichment analysis revealed 131 signaling pathways,including those related to malignant tumors,lipid and atherosclerosis,and AGE-RAGE signaling.Molecular docking results demonstrated favorable binding interactions between the core targets and the corresponding active components of Hippophae fructus.The in vitro experiments indicated that Hippophae fructus extract exhibited inhibitory effects on the proliferation of 3T3-L1 pre-adipocytes.Conclusion:This study reveals that Hippophae fructus exerts antiobesity effects through multiple components,targets,and pathways,providing valuable insights for its clinical research and product development.
作者
陆梦柯
王梓琴
张春
王菲
陈志玺
王亚妮
TANG Mengze
刘蕊
唐旭东
LU Mengke;WANG Ziqin;ZHANG Chun;WANG Fei;CHEN Zhixi;WANG Yani;TANG Mengze;LIU Rui;TANG Xudong(College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730000,China;Gannon Biotechnology Co.,Ltd.,Qingyang 745600,China;Boston University,Massachusetts 02215,USA;Key Laboratory of Innovative Traditional Chinese Medicine and Natural Medicine,Research Institute of Tsinghua University,Shenzhen 518000,China;Guangdong Innovative Traditional Chinese Medicine and Natural Medicine Research Engineering Center,Shenzhen 518000,China)
出处
《食品工业科技》
CAS
北大核心
2024年第6期1-11,共11页
Science and Technology of Food Industry
基金
深圳市出站博士后科研资助(2021年第三批)
深圳市中央引导地方发展专项(2022)。
关键词
沙棘
抗肥胖
网络药理
分子对接
3T3-L1
细胞
Hippophae fructus
anti-obesity
network pharmacology
molecular docking
3T3-L1 cells
