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[1]鄭春松,付長龍,林潔,等.應(yīng)用化合物-靶點(diǎn)網(wǎng)絡(luò)預(yù)測(cè)杜仲延緩軟骨退變的藥效物質(zhì)基礎(chǔ)及作用機(jī)制[J].中醫(yī)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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應(yīng)用化合物-靶點(diǎn)網(wǎng)絡(luò)預(yù)測(cè)杜仲延緩軟骨退變的藥效物質(zhì)基礎(chǔ)及作用機(jī)制()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第29卷
期數(shù):
2017年12期
頁碼:
6-10，18
欄目:
基礎(chǔ)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:
鄭春松1; 付長龍1; 林潔1; 吳廣文2; 李西海2; 葉蕻芝1; 劉獻(xiàn)祥1
1.福建中醫(yī)藥大學(xué),福建 福州 350122; 2.福建省中西醫(yī)結(jié)合老年性疾病重點(diǎn)實(shí)驗(yàn)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
關(guān)鍵詞:
杜仲;  骨關(guān)節(jié)炎;  軟骨; 關(guān)節(jié);  化合物-靶點(diǎn)網(wǎng)絡(luò);  藥理作用分子作用機(jī)制;  計(jì)算機(jī)模擬
Keywords:
Key words eucommia ulmoides;  osteoarthritis;  cartilage; articular;  compound-target network;  molecular mechanisms of pharmacological action;  computer simulation
摘要:
目的:探討杜仲延緩軟骨退變的藥效物質(zhì)基礎(chǔ)及作用機(jī)制。方法:通過檢索北京大學(xué)天然產(chǎn)物庫,檢索出杜仲中的化合物117個(gè),在Discovery studio模擬平臺(tái)上建立杜仲化合物分子數(shù)據(jù)集。通過檢索TTD數(shù)據(jù)庫和相關(guān)文獻(xiàn),確定白細(xì)胞介素(interleukin,IL)-1β、腫瘤壞死因子-α(tumor necrosis factor-α,TNF-α)、基質(zhì)金屬蛋白酶(matrix metalloproteinases,MMP)-1、MMP-3、轉(zhuǎn)化生長因子(transforming growth factor,TGF)-β1及聚蛋白多糖酶(a disintegrin and metalloproteinase with thrombospondin motifs,ADAMTS)-4為杜仲延緩軟骨退變的研究靶點(diǎn),從RCSB蛋白數(shù)據(jù)庫下載其蛋白質(zhì)-配體復(fù)合物結(jié)構(gòu),在Discovery studio模擬平臺(tái)上建立其蛋白分子數(shù)據(jù)集。利用分子對(duì)接和生物網(wǎng)絡(luò)技術(shù),構(gòu)建杜仲化合物-軟骨退變靶點(diǎn)作用網(wǎng)絡(luò),分析杜仲化合物與軟骨退變靶點(diǎn)的作用情況,辨識(shí)杜仲延緩軟骨退變的藥效物質(zhì)基礎(chǔ),并從杜仲化合物作用的靶點(diǎn)功能探討杜仲延緩軟骨退變的作用機(jī)制。結(jié)果:從杜仲化合物分子數(shù)據(jù)集中共篩選出70個(gè)化合物為杜仲延緩軟骨退變的藥效物質(zhì)基礎(chǔ),分別屬于環(huán)烯醚萜類、黃酮類和苯丙素類化合物。建立的杜仲化合物-軟骨退變靶點(diǎn)作用網(wǎng)絡(luò)中共有76個(gè)節(jié)點(diǎn)(包含70個(gè)杜仲化合物節(jié)點(diǎn)和6個(gè)靶點(diǎn)節(jié)點(diǎn))和200條邊,每個(gè)靶點(diǎn)的平均化合物數(shù)目為14個(gè),平均每個(gè)化合物能與2.9個(gè)靶點(diǎn)作用。IL-1β、MMP-1、TNF-α、MMP-3、ADAMTS-4、TGF-β1、UNPD197620(環(huán)烯醚萜類化合物)、UNPD20544(環(huán)烯醚萜類化合物)、UNPD197619(環(huán)烯醚萜類化合物)、UNPD156594(環(huán)烯醚萜類化合物)、UNPD67874(黃酮類化合物)、UNPD117238(黃酮類化合物)和UNPD182417(環(huán)烯醚萜類化合物)具有較高的度和介數(shù)值。結(jié)論:杜仲延緩軟骨退變的主要藥效物質(zhì)基礎(chǔ)為環(huán)烯醚萜類和黃酮類化合物,其作用機(jī)制可能是通過抑制軟骨中IL-1β、TNF-α的表達(dá)來減少軟骨中MMPs和ADAMTS的表達(dá),同時(shí)促進(jìn)TGF-β1的表達(dá),從而減少軟骨破壞、促進(jìn)軟骨修復(fù),最終延緩軟骨退變的進(jìn)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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備注/Memo

備注/Memo:
基金項(xiàng)目:國家自然科學(xué)基金面上項(xiàng)目(81573801); 福建省自然科學(xué)基金項(xiàng)目(2015J01338) 通訊作者:劉獻(xiàn)祥 E-mail:liuxianxiang@163
更新日期/Last Update: 2018-05-02