[1]李刚,许波,梁学振,等.杜仲防治骨关节炎的潜在活性成分及作用机制研究[J].中医正骨,2018,30(09):4-9.
　LI Gang,XU Bo,LIANG Xuezhen,et al.Potential active ingredients of eucommia ulmoides for prevention and treatment of osteoarthritis and its mechanism of action[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2018,30(09):4-9.
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杜仲防治骨关节炎的潜在活性成分及作用机制研究()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第30卷
期数:
2018年09期
页码:
4-9
栏目:
骨关节炎
出版日期:
2018-09-20

文章信息/Info

Title:
Potential active ingredients of eucommia ulmoides for prevention and treatment of osteoarthritis and its mechanism of action
作者:
李刚1; 许波2; 梁学振2; 骆帝2; 刘金豹2
1.山东中医药大学附属医院,山东 济南 250014; 2.山东中医药大学,山东 济南 250355
Author(s):
LI Gang1; XU Bo2; LIANG Xuezhen2; LUO Di2; LIU Jinbao2
1.The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China 2.Shandong University of Traditional Chinese Medicine,Jinan 250355,Shandong,China
关键词:
杜仲;  骨关节炎;  网络药理学;  活性成分;  药理作用分子作用机制
Keywords:
eucommia ulmoides;  osteoarthritis;  network pharmacology;  active ingredients;  molecular mechanisms of pharmacological action
摘要:
探讨杜仲防治骨关节炎的潜在活性成分及作用机制。方法:通过检索中药系统药理学数据库和分析平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)中杜仲所有成分数据,筛选和预测杜仲入血活性成分和作用靶点; 挖掘靶点数据库、药物银行、在线人类孟德尔遗传数据库、遗传关联数据库、药物遗传学和药物基因组学知识库5大疾病数据库中已知与骨关节炎相关的作用靶点; 构建杜仲入血活性成分及已知与OA相关靶点的相互关系网络,通过网络拓扑分析,筛选杜仲防治骨关节炎的关键靶点; 采用ClueGo信号通路富集,分析杜仲防治骨关节炎的作用机制。结果:通过TCMSP检索出119个杜仲相关成分,利用TCMSP模型预测出7个入血活性成分(槲皮素、β-谷甾醇、山奈酚、丁子香萜、刺痛灵、麦儿茶素、皮树脂醇)和116个作用靶点,且活性成分与作用靶点之间形成271条对应关系; 从5大疾病数据库检索出168个已知与骨关节炎相关的靶点; 网络拓扑分析筛选出202个杜仲防治OA的关键节点,其中疾病与药物直接映射靶点有17个; ClueGO富集分析结果显示,杜仲作用于骨关节炎的关键节点涉及的信号通路主要被富集于细胞周期、增殖和凋亡以及炎症、代谢、其他疾病相关等60条信号通路。结论:杜仲防治骨关节炎的活性成分主要为槲皮素、β-谷甾醇、山奈酚、丁子香萜、刺痛灵、麦儿茶素、皮树脂醇。其可能的作用机制不仅表现为直接参与细胞增殖、分化及凋亡,调节骨代谢平衡; 还表现为间接通过调节炎症、免疫和其他全身系统等,影响骨与软骨微环境,具有多通路、多成分、多靶点的特点。
Abstract:
To explore the potential active ingredients of eucommia ulmoides for prevention and treatment of osteoarthritis(OA)and its mechanism of action.Methods:All ingredients of eucommia ulmoides were screened for predicting the active ingredients and action targets of eucommia ulmoides by searching traditional chinese medicine systems pharmacology database and analysis platform(TCMSP).The known OA-related action targets were found out from target database(TTD),DrugBank,online Mendelian inheritance in man(OMIM),genetic association database(GAD)and pharmacogenetics and pharmacogenomics knowledge base(PharmGKB).The network of interaction between active ingredients of eucommia ulmoides and known OA-related action targets was built,and the key targets of eucommia ulmoides in prevention and treatment of OA were selected through network topology analysis.The mechanism of action of eucommia ulmoides in prevention and treatment of OA was analyzed by using ClueGo signaling pathways enrichment.Results:One hundred and nineteen eucommia ulmoides-related ingredients were searched out from TCMSP,and 7 active ingredients(quercetin,β-sitosterol,kaempferol,mairin,erythraline,ent-epicatechin and medioresinol)and 116 action targets were predicted by using TCMSP model,and 271 corresponding relationships between active ingredients and action targets were found.One hundred and sixty eight known OA-related action targets were searched out from the five disease databases,and 202 key nodes for prevention and treatment of OA with eucommia ulmoides were selected out by using network topology analysis,in which 17 disease-drug mapping targets were found.The results of ClueGO enrichment analysis showed that the signaling pathways associated with the key nodes of eucommia ulmoides that effected on OA were mainly concentrated in 60 signal pathways which related to cell cycle,cell proliferation and cell apoptosis,inflammation,metabolism and other diseases.Conclusion:The main active ingredients of eucommia ulmoides for prevention and treatment of OA are quercetin,β-sitosterol,kaempferol,mairin,erythraline,ent-epicatechin and medioresinol.They can directly regulate the bone metabolism balance by participating in cell proliferation,differentiation and apoptosis,and they can indirectly affect the micro-environment of bone and cartilage by regulating inflammation,immunity and other body systems,which may be their mechanisms of action.They have the characteristics of multiple pathways,multiple ingredients and multiple targets.

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备注/Memo

备注/Memo:
基金项目:山东省自然科学基金资助项目(ZR2017LH067)
更新日期/Last Update: 2018-09-20