基于网络药理学探讨桂枝-白芍药对治疗类风湿性关节炎作用机制
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R593.22

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浙江省中医药科研基金计划项目(2022ZB403,2020ZA123)


Discussion on Mechanism of Cinnamomi Ramulus-Paeoniae Radix Alba Couplet Medicinals in Treating Rheumatoid Arthritis Based on Network Pharmacology
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    摘要:

    目的:基于GEO 基因芯片、生物信息学及分子对接技术探讨桂枝-白芍药对治疗类风湿性关节炎(RA) 的作用机制。方法:通过GEO 数据库下载RA 的基因芯片数据集,利用R 软件筛选出差异表达靶点;通过TCMSP、PharmMapper 等数据库获取桂枝-白芍药对的化学成分、药物靶点,运用Cytoscape 3.9.1、R软件对药物-疾病交集靶点进行蛋白互作(PPI) 网络拓扑分析;应用clusterProfiler 等程序包对于交集靶点进行基因本体(GO)、京都基因和基因组(KEGG) 富集分析;使用AutoDock Vina 等软件进行分子对接初步验证。结果:共获得17 个药物化学成分,RA 靶点3 781 个、药物靶点410 个;筛选出药物-疾病交集靶点98 个。PPI 拓扑分析得出的核心靶点有基质金属蛋白酶-9 (MMP-9)、基质金属蛋白酶-2 (MMP-2)、过氧化氢酶(CAT)、丝氨酸蛋白酶抑制剂家族A 成员1(SERPINA1)、组织蛋白酶B(CTSB) 等;桂枝-白芍药对治疗RA 主要化学化合物有二氢槲皮素、β-谷甾醇、(+) -儿茶素、芍药苷等。潜在作用靶点参与了胶原分解代谢过程、细胞外基质分解、炎症反应调节等生物过程,涉及通路有溶酶体、过氧化物酶体增殖物激活受体(PPAR) 信号通路、细胞色素P450 代谢等。分子对接显示,桂枝-白芍药对主要化学化合物与核心靶点间结合能有较高的结合活性。结论:桂枝-白芍治疗RA 多靶点、多成分、多途径的作用机制,为桂枝-白芍药对的后续研究提供了理论依据。

    Abstract:

    Abstract:Objective:To discuss the mechanism of Cinnamomi Ramulus-Paeoniae Radix Alba couplet medicinals in treating rheumatoid arthritis(RA) based on GEO gene chip, bioinformatics and molecular docking. Methods: The gene chip data set of RA was downloaded from the GEO database, and the differential expression targets were screened by R software;databases,such as TCMSP and PharmMapper, were used to obtain the chemical components and targets of Cinnamomi Ramulus- Paeoniae Radix Alba couplet medicinals,and Cytoscape 3.9.1 and R software were used to carry out the topology analysis of the protein-protein interaction(PPI) network of medicine-disease intersection targets ; packages , including clusterProfiler package, were used to perform gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis on the intersection targets; softwares, such as AutoDock Vina, were used to perform molecular docking for preliminary validation. Results: A total of 17 chemical components of medicine,3 781 RA targets and 410 medicine targets were obtained;a total of 98 medicinedisease intersection targets were screened out. The core targets of topology analysis of PPI included matrix metalloproteinase- 9(MMP-9) , matrix metalloproteinase- 2(MMP-2) , catalase(CAT) , Serpin Family A Member 1(SERPINA1), cathepsin B(CTSB) and so on; the main chemical compounds of Cinnamomi Ramulus- Paeoniae Radix Alba couplet medicinals in treating RA are taxiflin,β- sitosterol,(+ ) - catechin, paeoniflorin and so on. Potential targets involved in collagen decomposition and metabolism,extracellular matrix decomposition, inflammatory response regulation and other biological processes, involving pathways such as lysosomes, peroxisome proliferator- activated receptor(PPAR) signaling pathway and cytochrome P450 metabolism. Molecular docking showed that Cinnamomi Ramulus- Paeoniae Radix Alba couplet medicinals had high binding activity between the main chemical compounds and the core targets. Conclusion:The multi-target,multi-component and multi-pathway mechanism of Cinnamomi Ramulus- Paeoniae Radix Alba in treating RA provides a theoretical basis for the follow- up study of Cinnamomi Ramulus-Paeoniae Radix Alba couplet medicinals.

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种凯艳,兰祝飚.基于网络药理学探讨桂枝-白芍药对治疗类风湿性关节炎作用机制[J].新中医,2022,54(23):1-7

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  • 在线发布日期: 2022-12-11
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