| 龚俊杰,徐子金,王平.基于网络药理学和分子对接探讨西红花治疗帕金森病的作用机制[J].浙江中医药大学学报,2023,47(12):1383-1394. |
| 基于网络药理学和分子对接探讨西红花治疗帕金森病的作用机制 |
| Mechanism of Saffron in Treatment of Parkinson’s Disease Based on Network Pharmacology and Molecular Docking |
| DOI：10.16466/j.issn1005-5509.2023.12.003 |
| 中文关键词: 西红花 帕金森病 网络药理学 分子对接 神经炎症 作用机制 |
| 英文关键词: Saffron Parkinson’s disease network pharmacology molecular docking neuroinflammation mechanism of action |
| 基金项目:政府间国际科技创新合作重点专项(2017YFE0130100) |
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| 中文摘要: |
| [目的] 基于网络药理学和分子对接，探究中药西红花(Saffron)对帕金森病(Parkinson’s disease，PD)的治疗作用及分子机制。[方法] 通过中药系统药理学数据库和文献调研，确定纳入分析的西红花药效成分；借助化合物靶点数据库和疾病靶点数据库，分别预测西红花成分对应的靶点和PD靶点；使用R程序和引用相关R包，对化合物-疾病的交集靶点进行富集分析；构建蛋白互作网络，分析节点相关拓扑参数；模拟分子对接过程，验证代表性化合物和关键靶点的结合特性。通过实验初步评估西红花酸对关键靶点作用的药效学性质。[结果] 西红花具有成药潜力的8种成分对应279个靶点，PD对应的疾病靶点有2 183个，获得化合物和疾病的交集靶点共98个。富集分析提示化合物-疾病交集靶点参与活性氧自由基的合成与代谢、神经炎症等生物过程和涉及丝裂原活化蛋白激酶信号通路等。蛋白互作网络分析确认的关键靶点为肿瘤坏死因子(tumor necrosis factor，TNF)和信号转导和转录激活因子3(signal transducer and activator of transcription 3，STAT3)。分子对接显示，西红花苷类和西红花酸类成分与TNF具有更强的结合活性。实验表明，西红花酸能降低脂多糖诱导的细胞炎性因子TNF、白细胞介素-1β(interleukin-1β，IL-1β)以及诱导型一氧化氮合酶(inducible nitric oxide synthase，iNOS)的转录水平。[结论] 西红花可作为PD治疗的候选中药，其神经保护作用可能涉及众多靶点和信号通路的交互协同，西红花酸抗中枢神经炎症的活性特别值得关注。 |
| 英文摘要: |
| [Objective] To investigate the therapeutic effect and molecular mechanism of Chinese medicine Saffron on Parkinson’s disease(PD) based on network pharmacology and molecular docking. [Methods] The pharmacodynamic components of Saffron included in the analysis were determined through the pharmacological database and literature research of the Chinese medicine system. With the help of compound target database and disease target database， the corresponding targets of saffron components and PD targets were predicted， respectively. Enrichment analysis of compound-disease intersection targets was made by using R procedures and referencing correlated R-packages. Construction of protein-protein interaction(PPI) networks and analysis of node-related topological parameters. Simulate molecular docking to verify binding properties of representative compounds and key targets. The pharmacodynamic properties of Saffron acid on key targets were preliminarily evaluated by experiments. [Results] The 8 components of saffron with druggable potential corresponded to 279 targets， PD had 2 183 disease targets， and a total of 98 intersection targets of compounds and diseases were obtained. Enrichment analysis showed that the compound-disease intersection target was involved in biological processes such as reactive oxygen radical synthesis and metabolism， neuroinflammation and mitogen-activated protein kinase(MAPK) signaling pathway. The key targets identified by PPI network analysis were tumor necrosis factor(TNF) and signal transducer and activator of transcription 3(STAT3). Molecular docking showed that saffron glycosides and saffron acids had stronger binding activity with TNF. Experiments had shown that saffron acid can reduce the transcription levels of lipopolysaccharide-induced cytoinflammatory factor TNF， interleukin-1β(IL-1β) and inducible nitric oxide oxide synthase(iNOS). [Conclusion] Saffron can be used as a candidate for PD treatment， and its neuroprotective effect may involve the interaction and synergy of many targets and signaling pathways， which deserves special attention to the activity of saffron acid against central nervous system inflammation. |
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