[1]郑春松,付长龙,林洁,等.应用化合物-靶点网络预测杜仲延缓软骨退变的药效物质基础及作用机制[J].中医正骨,2017,29(12):6-10，18.
　ZHENG Chunsong,FU Changlong,LIN Jie,et al.Application of compound-target network in predicting the pharmacodynamic material basis of eucommia ulmoides in delaying cartilage degeneration and its mechanism of action[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2017,29(12):6-10，18.
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应用化合物-靶点网络预测杜仲延缓软骨退变的药效物质基础及作用机制()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第29卷
期数:
2017年12期
页码:
6-10，18
栏目:
基础研究
出版日期:
2017-12-20

文章信息/Info

Title:
Application of compound-target network in predicting the pharmacodynamic material basis of eucommia ulmoides in delaying cartilage degeneration and its mechanism of action
作者:
郑春松1; 付长龙1; 林洁1; 吴广文2; 李西海2; 叶蕻芝1; 刘献祥1
1.福建中医药大学,福建 福州 350122; 2.福建省中西医结合老年性疾病重点实验室,福建 福州 350122
Author(s):
ZHENG Chunsong1; FU Changlong1; LIN Jie1; WU Guangwen2; LI Xihai2; YE Hongzhi1; LIU Xianxiang1
1.Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China 2.Fujian Key Laboratory of Integrated Medicine on Geriatrics,Fuzhou 350122,Fujian,China
关键词:
杜仲;  骨关节炎;  软骨; 关节;  化合物-靶点网络;  药理作用分子作用机制;  计算机模拟
Keywords:
Key words eucommia ulmoides;  osteoarthritis;  cartilage; articular;  compound-target network;  molecular mechanisms of pharmacological action;  computer simulation
摘要:
目的:探讨杜仲延缓软骨退变的药效物质基础及作用机制。方法:通过检索北京大学天然产物库,检索出杜仲中的化合物117个,在Discovery studio模拟平台上建立杜仲化合物分子数据集。通过检索TTD数据库和相关文献,确定白细胞介素(interleukin,IL)-1β、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶(matrix metalloproteinases,MMP)-1、MMP-3、转化生长因子(transforming growth factor,TGF)-β1及聚蛋白多糖酶(a disintegrin and metalloproteinase with thrombospondin motifs,ADAMTS)-4为杜仲延缓软骨退变的研究靶点,从RCSB蛋白数据库下载其蛋白质-配体复合物结构,在Discovery studio模拟平台上建立其蛋白分子数据集。利用分子对接和生物网络技术,构建杜仲化合物-软骨退变靶点作用网络,分析杜仲化合物与软骨退变靶点的作用情况,辨识杜仲延缓软骨退变的药效物质基础,并从杜仲化合物作用的靶点功能探讨杜仲延缓软骨退变的作用机制。结果:从杜仲化合物分子数据集中共筛选出70个化合物为杜仲延缓软骨退变的药效物质基础,分别属于环烯醚萜类、黄酮类和苯丙素类化合物。建立的杜仲化合物-软骨退变靶点作用网络中共有76个节点(包含70个杜仲化合物节点和6个靶点节点)和200条边,每个靶点的平均化合物数目为14个,平均每个化合物能与2.9个靶点作用。IL-1β、MMP-1、TNF-α、MMP-3、ADAMTS-4、TGF-β1、UNPD197620(环烯醚萜类化合物)、UNPD20544(环烯醚萜类化合物)、UNPD197619(环烯醚萜类化合物)、UNPD156594(环烯醚萜类化合物)、UNPD67874(黄酮类化合物)、UNPD117238(黄酮类化合物)和UNPD182417(环烯醚萜类化合物)具有较高的度和介数值。结论:杜仲延缓软骨退变的主要药效物质基础为环烯醚萜类和黄酮类化合物,其作用机制可能是通过抑制软骨中IL-1β、TNF-α的表达来减少软骨中MMPs和ADAMTS的表达,同时促进TGF-β1的表达,从而减少软骨破坏、促进软骨修复,最终延缓软骨退变的进程。
Abstract:
ABSTRACT Objective:To explore the pharmacodynamic material basis of eucommia ulmoides in delaying cartilage degeneration and its mechanism of action.Methods:One hundred and seventeen chemical compounds were searched out from eucommia ulmoides by searching Peking University Natural Product Library,and eucommia ulmoides chemical compound molecular datasets were built on the Discovery studio simulation platform.Interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),matrix metalloproteinases(MMP)-1,MMP-3,transforming growth factor(TGF)-β1 and a disintegrin and metalloproteinase with thrombospondin motifs(ADAMTS)-4 were identified as the research targets of eucommia ulmoides for delaying cartilage degeneration through retrieving TTD database and related literatures.Their protein-ligand compound structures were downloaded from RCSB protein database and the molecular datasets of protein were built on the Discovery studio simulation platform.The network of interaction between chemical compounds of eucommia ulmoides and targets of cartilage degeneration was built by using molecular docking and bio-network technology,and their interactions were analyzed.The pharmacodynamic .commaterial basis of eucommia ulmoides in delaying cartilage degeneration was identified,meanwhile,the mechanism of action of eucommia ulmoides in delaying cartilage degeneration was explored by analysing the role of target of eucommia ulmoides chemical compounds.Seventy chemical compounds selected from eucommia ulmoides chemical compound molecular datasets were identified as the pharmacodynamic material basis of eucommia ulmoides in delaying cartilage degeneration,and they belonged to iridoids,flavonoids and phenylpropanoids respectively.The network of interaction between chemical compound of eucommia ulmoides and targets of cartilage degeneration consisted of 76 nodes(included 70 eucommia ulmoides chemical compound nodes and 6 target nodes)and 200 edges in total.The average number of chemical compounds for each target was 14,and each chemical compound can act on 2.9 targets averagely.IL-1β,MMP-1,TNF-α,MMP-3,ADAMTS-4,TGF-β1,UNPD197620(iridoid),UNPD20544(iridoid),UNPD197619(iridoid),UNPD156594(iridoid),UNPD67874(flavonoid),UNPD117238(flavonoid)and UNPD182417(iridoids)had comparatively high degrees and betweenness values.Conclusion:The main pharmacodynamic material basis of eucommia ulmoides in delaying cartilage degeneration are iridoids and flavonoids.They can reduce the expression of MMPs and ADAMTS and promote the expression of TGF-β1 in cartilage through inhibiting the expression of IL-1β and TNF-α,which may be the mechanisms of action for reducing the damage of cartilage,promoting the repair of cartilage and delaying the process of cartilage degeneration ultimately.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金面上项目(81573801); 福建省自然科学基金项目(2015J01338) 通讯作者:刘献祥 E-mail:liuxianxiang@163
更新日期/Last Update: 2018-05-02