泽泻醇A对HepG2细胞脂质沉积的影响及其降脂活性研究  

Effect of alisol A on lipid deposition in HepG2 cells and its hypolipidemic activity research

作　　者：颜伟泓 张鸿燕 李玲燕 曾敏洁 吴艺锦 陈全成[3] 张伟云 YAN Weihong;ZHANG Hongyan;LI Lingyan;ZENG Minjie;WU Yijin;CHEN Quancheng;ZHANG Weiyun(Department of Pharmacy,Xiamen Medical College,Xiamen,Fujian 361023,China;School of Pharmacy,Fujian Medical University,Fuzhou,Fujian 350122,China;School of Pharmaceutical Sciences,Xiamen University,Xiamen,Fujian 361102,China)

机构地区：[1]厦门医学院药学系,福建厦门361023 [2]福建医科大学药学院,福建福州350122 [3]厦门大学药学院,福建厦门361102

出　　处：《上海中医药杂志》2024年第10期63-70,共8页Shanghai Journal of Traditional Chinese Medicine

基　　金：福建省自然科学基金项目(2023J011656);福建省大学生创新创业项目(202412631006,202412631028);厦门市医疗卫生指导性项目(3502Z20224ZD1309);厦门医学院校级一流课程项目(XBJK2021027,XBJK2023012);厦门医学院大学生创新创业项目(202412631042,202412631045)。

摘　　要：目的通过体外细胞实验、网络药理学和分子对接技术,探究泽泻醇A的降脂作用机制。方法选用人肝癌HepG2细胞进行油红O染色实验和胆固醇(TC)、三酰甘油(TG)含量测定,初步判断泽泻醇A是否具有改善HepG2细胞脂质沉积的活性;通过网络药理学收集泽泻醇A和降血脂的靶点,根据二者的交集靶点绘制蛋白-蛋白相互作用(PPI)网络和“泽泻醇A-潜在靶点-降血脂-通路”网络,并进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,最后将泽泻醇A与降血脂潜在靶点进行对接。结果细胞实验结果提示,泽泻醇A抑制了油酸-棕榈酸诱导的HepG2高脂细胞模型的脂质沉积;通过网络药理学筛选出泽泻醇A的11个降血脂潜在靶点,靶点蛋白富集通路主要有过氧化物酶体增殖物激活受体(PPAR)信号通路等;分子对接结果显示泽泻醇A和潜在靶点具有较强结合活性。结论泽泻醇A可抑制HepG2高脂细胞模型的脂质沉积,推测其可能具有降脂活性,作用机制可能涉及PPAR等多个信号通路和丝氨酸/苏氨酸蛋白激酶1(AKT1)等11个靶点,为今后研究泽泻醇A降脂活性及作用机制提供理论基础。Objective To explore the hypolipidemic mechanism of alisol A based on in vitro cell experiment,network pharmacology and molecular docking technology.Methods HepG2 cells were selected for oil red O staining and the measurement of total cholesterol(TC)and triglyceride(TG)to preliminarily assess whether alisol A could improve lipid deposition in HepG2 cells.The potential targets of alisol A and hypolipidemic activity were identified through network pharmacology.The protein-protein interaction(PPI)network and an"alisol A-potential target-hypolipidemic activitypathway"network were constructed based on the intersection targets.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted.Finally,alisol A was docked with the identified potential targets of hypolipidemic activity.Results The cell experiment results showed that alisol A inhibited lipid deposition in an OA/PA-induced high-lipid HepG2 cell model.Network pharmacology identified 11 potential targets of hypolipidemic activity of alisol A.The target proteins were primarily enriched in pathways such as the peroxisome proliferatoractivated receptor(PPAR)signaling pathway.The results of molecular docking showed that alisol A and potential targets had strong binding activity.Conclusion Alisol A effectively inhibited lipid deposition in a high-lipid HepG2 cell model,suggesting its potential hypolipidemic activity.The mechanism of action may involve multiple signaling pathways,including the PPAR signaling pathway and 11 targets such as serine/threonine kinase 1(AKT1).These findings provide a theoretical basis for further research into the hypolipidemic activity and mechanism of alisol A.

关 键 词：高脂血症 泽泻醇A 降脂机制 HEPG2细胞 网络药理学 分子对接 中药研究 

分 类 号：R285[医药卫生—中药学]