| 基于网络药理学与分子对接探讨木瓜治疗膝骨关节炎的分子机制 |
| 投稿时间：2019-09-09 点此下载全文
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| 引用本文：时孝晴,梅伟,茆军,张农山,邢润麟,殷松江,王培民.基于网络药理学与分子对接探讨木瓜治疗膝骨关节炎的分子机制[J].中国现代中药,2020,22(9):1502-1510 |
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| 基金项目:国家自然科学基金项目（81774334）；江苏省中医药领军人才（SLJ0207）；江苏省研究生科研与实践创新计划项目（SJCX19_0354） |
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| 中文摘要:目的：基于网络药理学探索木瓜治疗膝骨性关节炎的分子作用机制。方法：基于口服生物利用度（OB）及药物相似性（DL），通过中药系统药理学数据库（TCMSP）筛选木瓜的主要活性成分。运用GeneCards、OMIM数据库建立膝骨性关节炎靶标数据库。通过Cytoscape 3.7.1软件构建“活性成分-作用靶标-疾病”可视化交互网络；运用STRING数据库构建蛋白互作网络，分析相关蛋白互作关系；对核心靶点进行京都基因与基因百科全书（KEGG）通路及基因本体（GO）生物过程富集分析。通过Discovery Studio软件对药物活性成分与疾病靶点进行分子对接验证。结果：筛选得到木瓜活性成分3个，涉及44个作用靶点。网络分析结果表明，靶点主要涉及调节细胞代谢、凋亡等生物学过程，通过调节细胞凋亡、肿瘤坏死因子（TNF）、p53、核转录因子-κB（NF-κB）、糖基化终末产物（AGE）及其受体（RAGE）等信号通路来发挥治疗膝骨关节炎的作用。分子对接结果表明，木瓜活性成分与膝骨性关节炎的血管内皮生长因子A（VEGFA）、白细胞介素-6（IL-6）、雌激素受体1（ESR1）等靶点对接吻合度较好。结论：木瓜治疗膝骨性关节炎具有多系统、多成分、多靶点的特点；其可能的作用机制包括控制炎症，调控关节软骨代谢、生长和修复，促进细胞增殖、分化，抑制细胞凋亡和抵抗氧化应激等以达到控制疾病发生发展的目的；木瓜中槲皮素、白桦脂酸、表儿茶酸等活性成分可能是其治疗膝骨性关节炎的物质基础。 |
| 中文关键词:木瓜 膝骨关节炎 网络药理学 机制预测 分子对接 |
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| Molecular Mechanism of Chaenomelis Fructus in Treatment of Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking |
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| Abstract:Objective：To explore the molecular mechanism of Chaenomelis Fructus in the treatment of knee osteoarthritis based on network pharmacology. Methods：Based on oral bioavailability and drug similarity，the main active ingredients of Chaenomelis Fructus were screened by TCMSP. GeneCard and OMIM database were used to establish the target database of knee osteoarthritis. Cytoscape 3.7.1 software was used to construct a visual interactive network map of ″active ingredient-action target-disease″. STRING database was used to construct protein interaction network and analyze the interaction relationship between related proteins；Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene ontology （GO） bioaccumulation analysis were carried out for core targets. In addition，the drug active ingredients were docked with disease targets by Discovery Studio software. Results：Three active ingredients of Chaenomelis Fructus were screened，involving 44 targets. The results of network analysis revealed that these targets exerted their therapeutic effects on knee osteoarthritis by regulating cell apoptosis，TNF，p53，NF-kappa B，AGE-RAGE and other signaling pathways which mainly involved in the cell metabolism，apoptosis and other biological processes. Molecular docking results showed that the docking degree of papaya active ingredients with targets of KOA such as VEGFA，IL6，ESR1 was good. Conclusion：Chaenomelis Fructus had the characteristics of multi-system，multi-component and multi-target in the treatment of knee osteoarthritis. Possible mechanisms include controlling inflammation，regulating the metabolism，growth and repairment of articular cartilage，promoting cell proliferation and differentiation，inhibiting cell apoptosis and resisting oxidative stress which could control the occurrence and development of disease. Mairin，ent-epicatechin，and quercetin in Chaenomelis Fructus may be the material basis for the treatment of knee osteoarthritis. |
| keywords:Chaenomelis Fructus knee osteoarthritis network pharmacology mechanism prediction molecular docking |
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