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目的:基于网络药理学和体外实验探讨丹参-川芎治疗动脉粥样硬化的主要化学成分及其作用机制。方法:TCMSP数据库筛选并收集丹参-川芎的化学成分及其对应靶标，使用Cytoscape 3.7.2软件绘制药物-活性成分-交集靶点网络图，利用Metascape数据库对丹参-川芎治疗动脉粥样硬化的潜在作用靶标进行GO分类富集分析和KEGG通路富集分析。使用UCSF CHIMERA软件进行分子对接，选择最佳的结合靶点。通过细胞实验验证丹参-川芎药对的抗动脉粥样硬化作用。结果:从丹参-川芎中共得到72个候选活性成分，包括木犀草素、丹参酮IIA、二氢丹参内酯、杨梅酮、丹参新醌等，与动脉粥样硬化相关的潜在作用靶标67个，包括AKT1、IL6、VEGFA、MAPK1、TP53等，主要的信号通路有癌症通路、PI3K-AKT信号通路、流体剪切应力与动脉粥样硬化通路、JAK-STAT信号通路、炎症性肠病、NF-κB信号通路、脂肪细胞脂解的调节等信号通路。细胞实验结果表明，丹参-川芎药对可减少巨噬细胞的泡沫化，降低AKT1、ERK1/2蛋白的磷酸化水平，抑制VEGFA的蛋白表达发挥抗动脉粥样硬化作用。结论:丹参-川芎治疗动脉粥样硬化具有多靶点、多通路的特点，其机制可能与调控AKT1、ERK1/2、VEGFA的蛋白表达有关。
Abstract：Objective:To explore the main components and mechanism of Danshen-Chuanxiong medicinal pair in the treatment of atherosclerosis based on network pharmacology and in vitro experiment. Methods:Traditional Chinese Medicinal Systems Pharmacology Database and Analysis Platform(TCMSP) was used to screen and collect the chemical components of Danshen-Chuanxiong medicinal pair and the corresponding targets, and Cytoscape 3.7.2 was used to draw a drug-active component-target network. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out by Metascape to analyze the potential targets of Danshen-Chuanxiong medicinal pair in the treatment of atherosclerosis. UCSF Chimera was applied for molecular docking to select the optimal binding targets. The anti-atherosclerotic effect of Danshen-Chuanxiong medicinal pair was verified through the cellular experiment. Results:Seventy-two active component candidates, including luteolin, tanshinone IIA,dihydrotanshinlactone, myricetin, and neotanshinone, were obtained from Danshen-Chuanxiong medicinal pair. Sixty-seven potential targets related to atherosclerosis, including protein kinase B1(AKT1),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),mitogen-activated protein kinase 1(MAPK1),and tumor protein p53(TP53),were obtained. The main signaling pathways involved cancer, phosphoinositide 3 kinase-protein kinase B(PI3 K-AKT),shear stress and atherosclerosis, Janus kinase-signal transducer and activator of transcription protein(JAK-STAT),inflammatory bowel disease, nuclear factor kappa B(NF-κB),regulation of adipocyte lipolysis, etc. The results of the cellular experiment showed that Danshen-Chuanxiong medicinal pair could play an anti-atherosclerotic role by decreasing the macrophage foaming, reducing the phosphorylation level of AKT1 and extracellular signal-regulated kinase 1/2(ERK1/2) proteins, and inhibiting the expression of VEGFA protein. Conclusion:Danshen-Chuanxiong medicinal pair has multi-target and multi-pathway characteristics in the treatment of atherosclerosis. The mechanism may be related to the regulation of protein expression of AKT1,ERK1/2,and VEGFA.
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基本信息:
DOI：10.13412/j.cnki.zyyl.20220324.001
中图分类号:R285.6
引用信息:
[1]王钰莹,王川,胡锐,等.基于网络药理学和体外实验探讨丹参-川芎药对治疗动脉粥样硬化的作用机制[J].中药药理与临床,2022,38(04):67-73.DOI:10.13412/j.cnki.zyyl.20220324.001.
基金信息:
国家自然科学基金项目(编号：81800401); 陕西省科技厅科技计划项目(编号：2021SF-368、2022SF-435、2022SF-207); 大学生创新创业训练计划项目(编号：S202010716021); 陕西中医药大学学科创新团队项目(编号：2019-YL13)
2022-03-25
2022-03-25
2022-03-25