川芎挥发油治疗心绞痛的网络药理学研究及实验验证
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1.江西中医药大学 药学院;2.江西中医药大学 临床医学院

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基于PI3K-Akt-mTOR-自噬通路研究冠心苏合丸“脑心同治”的分子机制(NO. 2022WBZR001)和复方川芎挥发油微乳喷雾剂“心脑同治”干预心绞痛作用机制的研究(NO. GJJ211236)


Network pharmacological study and experimental validation of Rhizoma Chuanxiong volatile oil in the treatment of angina pectoris
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1.Jiangxi University of Chinese Medicine, School of Pharmacy, Nanchang;2.Jiangxi University of Chinese Medicine, Clinical Medical College, Nanchang

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    摘要:

    目的 基于网络药理学研究川芎挥发油抗心绞痛的作用机制,并动物实验验证。方法 通过水蒸气蒸馏法、GC-MS、ADME参数共筛出挥发油成分;使用Pubchem、SwissTarget、DisGeNET、DrugBank数据库和R语言分别获取挥发油成分的靶点、心绞痛的靶点和交集靶点;蛋白质-蛋白质相互作用通过String数据库完成;使用R语言的clusterProfiler包对交集靶点进行GO和KEGG富集分析,并通过Cytoscape构建中药-成分-靶点-通路网络;借助AutoDock vina v1.2.3、Pymol、Discovery Studio 2016软件进行分子对接,分析关键靶点和主要挥发油成分的亲和力。最后,通过动物实验进一步验证川芎挥发油对心绞痛的治疗作用。结果 实验共得到10个挥发油成分和22个关键靶点,这些靶点与神经递质、突触膜上的受体、物质代谢等生物过程以及神经活性配体-受体相互作用、视黄醇代谢、药物代谢-细胞色素P450等通路密切相关;分子对接结果表明3-butylidenephthalide、Alpha-selinene、Trans-ligustilide等挥发油成分与多个关键靶点结合发挥治疗作用。动物实验说明川芎挥发油通过调节EF、FS、SV、LVIDs水平以及LDH、CK、AST活性,促进受损心肌细胞中ADRA1A、CHRM5蛋白的表达;改善心肌纤维状态,减小细胞间隙,减少炎性细胞浸润表现出保护心肌的作用。结论 综上所述,川芎挥发油有效保护受损心肌组织,发挥治疗心绞痛的作用。

    Abstract:

    Objective Based on network pharmacology and animal experiments, this study aims to study and verify the therapeutic effect of the volatile oil of Rhizoma Chuanxiong on angina pectoris. Methods Volatile oil components were screened out by steam distillation, GC-MS and ADME parameters. Using Pubchem, SwissTarget, DisGENET, DrugBank database and R language to obtain the target of volatile oil components, angina pectoris target and intersection target respectively; Protein-protein interaction is completed through the String database; The clusterProfiler package of R language was used to analyze the GO and KEGG enrichment of the intersecting targets and construction of herbal-component-target-pathway networks by Cytoscape. Molecular docking using AutoDock vina, Pymol and Discovery Studio 2016 software, molecular docking was carried out to analyze the affinity between key targets and main volatile oil components. Finally, the therapeutic effect of volatile oil of Rhizoma Chuanxiong on angina pectoris was further verified by animal experiments. Results There were 10 volatile oil components and 22 key targets, which were closely related to neurotransmitters, receptors on synaptic membranes, material metabolism, neuroactive ligand-receptor interaction, retinol metabolism, drug metabolism-cytochrome P450 pathways. Molecular docking results showed that 3-butylidenephthalide, Alpha-selinene, Trans-ligustilide and other volatile oil components combined with several key targets play a therapeutic role. Animal experiments show that the volatile oil of Rhizoma Chuanxiong can regulate the levels of EF, FS, SV, LVIDs and the activities of LDH, CK and AST; and promote the expression of ADRA1A and CHRM5 proteins in damaged cardiomyocytes; improve the state of myocardial fibers, reduce intercellular space, and reduce inflammatory cells Infiltration appears to protect the myocardium. Conclusion In summary, the volatile oil of Ligusticum wallichii can effectively protect the damaged myocardial tissue and play a role in treating angina pectoris.

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  • 收稿日期:2024-01-02
  • 最后修改日期:2024-04-03
  • 录用日期:2024-05-08
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