摘要
目的基于网络药理学、分子对接结合动物实验验证桃仁-红花药对干预动脉粥样硬化(atherosclerosis,AS)的作用机制。方法利用TCMIP v2.0平台获得桃仁-红花药对化学成分及其候选靶标,通过蛋白质相互作用(PPI)分析筛选获得桃仁-红花干预动脉粥样硬化的潜在活性成分及核心靶标,对核心靶标进行基因本体(GO)及基因组百科全书(KEGG)通路富集分析探讨其作用机制,采用Cytoscape软件构建“中药材-成分-核心靶标-作用通路”多维关联可视化网络,通过对网络进行分析获得关键活性成分及靶标;采用AutoDock对部分化合物及靶标进行分子对接验证;利用ApoE^(-/-)雄性小鼠高脂饮食喂养8周建立动脉粥样硬化模型进行实验验证。结果获得桃仁-红花49个活性成分,预测得到256个共同作用靶标,通过与1399个AS疾病相关靶标进行交集映射,获得其干预AS的74个靶标,核心靶标35个,主要为蛋白激酶B1(AKT1)、过氧化物酶体增殖物激活受体α(PPARA)、核转录因子κB(NF-κB)、Toll样受体4(TLR4)等。关键通路为PI3K-Akt信号通路和甲状腺激素信号通路等。分子对接结果显示关键化合物和关键靶标能够直接相互作用。实验结果表明,中、高剂量桃仁-红花可降脂(P<0.01),减轻主动脉内膜损伤,降低白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)含量(P<0.01),抑制关键靶标TLR4、NF-κB、AKT蛋白表达(P<0.01,P<0.05)。结论该研究从网络药理学角度预测了桃仁-红花改善AS的分子机制,初步证实其可下调TLR4、NF-κB、AKT蛋白表达,对抗AS,为其临床研究提供了理论基础。
Objective To verify the mechanism of Persicae Semen-Carthami Flos drug pair in the intervention of atherosclerosis(AS)based on network pharmacology,molecular docking and animal experiments.MethodsTCMIP v2.0 platform was used to obtain the chemical components and candidate targets of Persicae Semen-Carthami Flos,and the potential active components and core targets of Persicae Semen-Carthami Flos for the intervention of atherosclerosis were screened through protein-protein interaction(PPI)analysis.We conducted Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the core target to explore its action mechanism.A multi-dimensional visualization network of“Chinese medicinal material-componentcore target-action pathway”was built by using Cytoscape software,and the key active components and targets were obtained by analyzing the network.AutoDock was used for molecular docking verification of some compounds and targets.The atherosclerotic model was established by feeding ApoE^(-/-)male mice with high-fat diet for 8 weeks,which was used for further experimental verification.ResultsA total of 49 active components of Persicae SemenCarthami Flos and 256 common targets were predicted,and 74 targets and 35 core targets(AKT1,PPARA,NF-κB,TLR4,etc.)for the intervention of AS were obtained through mapping the intersection of 1399 disease-related targets.The key pathways obtained by KEGG enrichment analysis are PI3K-Akt signal pathway and thyroid hormone signal pathway.Molecular docking results showed that key compounds and key targets can interact directly.The experimental results showed that medium-and high-dose Persicae Semen-Carthami Flos could significantly reduce the lipid level(P<0.01),alleviate the injury of aortic intima,decrease IL-6 and TNF-αcontent(P<0.01),and inhibit the protein expression of TLR4,NF-κB and AKT(P<0.01,P<0.05).ConclusionThis study predicted the molecular mechanism of Persicae Semen-Carthami Flos on improving AS from the perspective of network pharmacolo
作者
方欢乐
陈衍斌
张鑫
刘小溪
周亚明
杜霞
FANG Huanle;CHEN Yanbin;ZHANG Xin;LIU Xiaoxi;ZHOU Yaming;DU Xia(Medical College of Xi'an Peihua University,Xi'an 710125 Shaanxi,China;Scientific Research Department of Buchang Pharma Co.,Ltd,Xi'an 710075 Shaanxi,China;Shaanxi Academy of Traditional Chinese Medicine,Xi'an 710003 Shaanxi,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2023年第9期1245-1254,共10页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
陕西省重点研发计划项目(2021SF-362,2023-YBSF-365)
陕西省自然科学基础研究计划项目(2022JQ-971)
陕西省教育厅重点科研协同创新中心项目(21JY001)
陕西省自然科学基础研究计划项目(2022JQ-919)。
关键词
桃仁-红花
动脉粥样硬化
网络药理学
分子对接
实验验证
小鼠
Persicae Semen-Carthami Flos
atherosclerosis
network pharmacology
molecular docking
experimental verification
mice
