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[1]李剛,許波,梁學(xué)振,等.杜仲防治骨關(guān)節(jié)炎的潛在活性成分及作用機(jī)制研究[J].中醫(yī)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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杜仲防治骨關(guān)節(jié)炎的潛在活性成分及作用機(jī)制研究()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第30卷
期數(shù):
2018年09期
頁(yè)碼:
4-9
欄目:
骨關(guān)節(jié)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:
李剛1; 許波2; 梁學(xué)振2; 駱帝2; 劉金豹2
1.山東中醫(yī)藥大學(xué)附屬醫(yī)院,山東 濟(jì)南 250014; 2.山東中醫(yī)藥大學(xué),山東 濟(jì)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
關(guān)鍵詞:
杜仲;  骨關(guān)節(jié)炎;  網(wǎng)絡(luò)藥理學(xué);  活性成分;  藥理作用分子作用機(jī)制
Keywords:
eucommia ulmoides;  osteoarthritis;  network pharmacology;  active ingredients;  molecular mechanisms of pharmacological action
摘要:
探討杜仲防治骨關(guān)節(jié)炎的潛在活性成分及作用機(jī)制。方法:通過(guò)檢索中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫(kù)和分析平臺(tái)(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)中杜仲所有成分?jǐn)?shù)據(jù),篩選和預(yù)測(cè)杜仲入血活性成分和作用靶點(diǎn); 挖掘靶點(diǎn)數(shù)據(jù)庫(kù)、藥物銀行、在線(xiàn)人類(lèi)孟德?tīng)栠z傳數(shù)據(jù)庫(kù)、遺傳關(guān)聯(lián)數(shù)據(jù)庫(kù)、藥物遺傳學(xué)和藥物基因組學(xué)知識(shí)庫(kù)5大疾病數(shù)據(jù)庫(kù)中已知與骨關(guān)節(jié)炎相關(guān)的作用靶點(diǎn); 構(gòu)建杜仲入血活性成分及已知與OA相關(guān)靶點(diǎn)的相互關(guān)系網(wǎng)絡(luò),通過(guò)網(wǎng)絡(luò)拓?fù)浞治?篩選杜仲防治骨關(guān)節(jié)炎的關(guān)鍵靶點(diǎn); 采用ClueGo信號(hào)通路富集,分析杜仲防治骨關(guān)節(jié)炎的作用機(jī)制。結(jié)果:通過(guò)TCMSP檢索出119個(gè)杜仲相關(guān)成分,利用TCMSP模型預(yù)測(cè)出7個(gè)入血活性成分(槲皮素、β-谷甾醇、山奈酚、丁子香萜、刺痛靈、麥兒茶素、皮樹(shù)脂醇)和116個(gè)作用靶點(diǎn),且活性成分與作用靶點(diǎn)之間形成271條對(duì)應(yīng)關(guān)系; 從5大疾病數(shù)據(jù)庫(kù)檢索出168個(gè)已知與骨關(guān)節(jié)炎相關(guān)的靶點(diǎn); 網(wǎng)絡(luò)拓?fù)浞治龊Y選出202個(gè)杜仲防治OA的關(guān)鍵節(jié)點(diǎn),其中疾病與藥物直接映射靶點(diǎn)有17個(gè); ClueGO富集分析結(jié)果顯示,杜仲作用于骨關(guān)節(jié)炎的關(guān)鍵節(jié)點(diǎn)涉及的信號(hào)通路主要被富集于細(xì)胞周期、增殖和凋亡以及炎癥、代謝、其他疾病相關(guān)等60條信號(hào)通路。結(jié)論:杜仲防治骨關(guān)節(jié)炎的活性成分主要為槲皮素、β-谷甾醇、山奈酚、丁子香萜、刺痛靈、麥兒茶素、皮樹(shù)脂醇。其可能的作用機(jī)制不僅表現(xiàn)為直接參與細(xì)胞增殖、分化及凋亡,調(diào)節(jié)骨代謝平衡; 還表現(xiàn)為間接通過(guò)調(diào)節(jié)炎癥、免疫和其他全身系統(tǒng)等,影響骨與軟骨微環(huán)境,具有多通路、多成分、多靶點(diǎn)的特點(diǎn)。
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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備注/Memo

備注/Memo:
基金項(xiàng)目:山東省自然科學(xué)基金資助項(xiàng)目(ZR2017LH067)
更新日期/Last Update: 2018-09-20