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[1]譚雪,許云騰,王圣杰,等.基于網絡藥理學方法探討二至丸治療骨質疏松癥的有效成分、作用靶點及作用機制[J].中醫(yī)正骨,2020,32(12):1-10.
　TAN Xue,XU Yunteng,WANG Shengjie,et al.A study of effective components,action targets and mechanism of action of Erzhi Wan(二至丸)for treatment of osteoporosis using network pharmacology approach[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2020,32(12):1-10.
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基于網絡藥理學方法探討二至丸治療骨質疏松癥的有效成分、作用靶點及作用機制()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第32卷
期數:
2020年12期
頁碼:
1-10
欄目:
基礎研究
出版日期:
2020-12-20

文章信息/Info

Title:
A study of effective components,action targets and mechanism of action of Erzhi Wan(二至丸)for treatment of osteoporosis using network pharmacology approach
作者:
譚雪1; 許云騰1; 王圣杰1; 王麗麗1; 付長龍2; 葉錦霞1; 鄭春松1; 葉蕻芝2; 李西海2
(1.福建中醫(yī)藥大學中西醫(yī)結合研究院,福建 福州 350122; 2.福建省中西醫(yī)結合老年性疾病重點實驗室,福建 福州 350122)
Author(s):
TAN Xue1; XU Yunteng1; WANG Shengjie1; WANG Lili1; FU Changlong2; YE Jinxia1; ZHENG Chunsong1; YE Hongzhi2; LI Xihai2
1.Academy of Integrated Medicine affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China2.Fujian Key Laboratory of Integrated Medicine on Geriatrics,Fuzhou 350122,Fujian,China
關鍵詞:
骨質疏松;  二至丸;  網絡藥理學
Keywords:
osteoporosis;  Erzhi Pill;  network pharmacology
摘要:
目的:探討二至丸治療骨質疏松癥(osteoporosis,OP)的有效成分、作用靶點及作用機制。方法:在GEO數據庫檢索OP相關基因,同時在中藥系統(tǒng)藥理學數據庫及分析平臺檢索二至丸的組成中藥(女貞子、墨旱蓮)的有效成分和藥物靶點。利用PERL軟件將檢索到的OP相關基因與二至丸的藥物靶點取交集,初步獲得二至丸治療OP的靶點。在此基礎上利用Cytoscape軟件建立二至丸治療OP的有效成分-靶點網絡進行分析,并利用R軟件進行靶點基因GO功能富集分析和KEGG通路富集分析。最后使用PERL軟件篩選出KEGG富集分析表達位于前20的信號通路和對應的靶點基因,利用Cytoscape軟件構建二至丸治療OP的信號通路-靶點關系網絡進行分析。結果:在GEO數據庫中篩選出2個與OP相關的基因芯片,分別為GSE35956和GSE56116,其共同的OP相關基因102個、共同上調基因34個、共同下調基因17個。利用PERL軟件將2個芯片中的OP相關基因與二至丸的藥物靶點取交集,共篩選出二至丸治療OP的42個靶點,其中芯片GSE35956對應的靶點28個、芯片GSE56116對應的靶點16個。2個芯片對應的有效成分-靶點網絡中,存在7個共同有效成分,分別為紫鉚素、槲皮素、山奈酚、β-谷甾醇、木犀草素、花旗松素和Lucidumoside D_qt; 存在2個共同靶點,分別為谷胱甘肽s-轉移酶mu1(glutathione S-transferase mu1,GSTM1)和GSTM2。靶點基因GO功能分析顯示,靶點基因的分子功能主要包括谷胱甘肽結合、寡肽結合、谷胱甘肽轉移酶活性、與修飾的氨基酸結合。靶點基因KEGG富集分析及信號通路-靶點關系網絡顯示,二至丸治療OP的主要靶點基因包括CDKN1A、CHUK、MYC、RELA、GSTM1、GSTM2、FOS、IL4、CD40LG,其中CDKN1A、GSTM1、GSTM2、RELA、MYC、FOS是上調基因,CHUK、CD40LG、IL4是下調基因; 2個芯片中共同的靶點基因為GSTM1和GSTM2,且在2個芯片中都屬于上調基因; 二至丸治療OP的主要信號通路為與感染、心血管疾病、癌癥、代謝、免疫相關的信號通路。結論:二至丸治療OP的有效成分主要為黃酮類化合物,主要靶點為GSTM1和GSTM2,其作用機制可能是通過抑制或減輕氧化應激反應發(fā)揮治療作用。
Abstract:
To explore the effective components,action targets and mechanism of action of Erzhi Wan(二至丸,EZW)for treatment of osteoporosis(OP).Methods:The OP-related genes were searched out from GEO databases,and the effective components and drug targets of EZW(Fructus Ligustri Lucidi and Ecliptae Herba)were screened out by retrieving Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The targets of EZW for treatment of OP were selected out through overlapping the retrieved OP-related genes with the drug targets of EZW using PERL software.The effective components-targets network of EZW for treatment of OP was built by using Cytoscape software,and GO function and KEGG pathway enrichment analysis were performed on target genes respectively by using R software.Finally,the top 20 signal pathways and their corresponding target genes obtained by KEGG enrichment analysis were screened out by using PERL software,and the signal pathway-target interaction network of EZW for treatment of OP was built by using Cytoscape software.Results:Two OP-related gene chips including GSE35956 and GSE56116 were searched out from GEO databases,and 102 common OP-related genes,34 common up-regulated genes and 17 common down-regulated genes were found in the 2 chips.Forty-two targets of EZW for treatment of OP were selected out through overlapping the OP-related genes in 2 chips with the drug targets of EZW by using PERL software,in which GSE35956 corresponded to 28 targets and GSE56116 corresponded to 16 targets.Seven common effective components including butin,quercetin,kaempferol,beta-sitosterol,luteolin,taxifolin and Lucidumoside D_qt and 2 common targets including glutathione S-transferase mu 1(GSTM1)and GSTM2 were found in the effective components-targets network that corresponded to the 2 chips.The results of GO function enrichment analysis on target genes demonstrated that the main molecular functions of target genes included glutathione binding,oligopeptide binding,glutathione transferase activity and modified amino acid binding.The results of KEGG pathway enrichment analysis on target genes and the signal pathway-target interaction network demonstrated that the main target genes of EZW for treatment of OP included CDKN1A,CHUK,MYC,RELA,GSTM1,GSTM2,FOS,IL4 and CD40LG,in which CDKN1A,GSTM1, GSTM2, RELA,MYC and FOS were up-regulated genes,while CHUK, CD40LG and IL4 were down-regulated genes.The common target genes were up-regulated genes GSTM1 and GSTM2 in the 2 chips.The main signal pathways of EZW for treatment of OP were the signal pathways which related to infection,cardiovascular disease,cancer,metabolism and immunity.Conclusion:The effective components of EZW are mainly flavonoids,and the main targets are GSTM1 and GSTM2 in treatment of OP.Its mechanism of action may be that it produce the therapeutic effects through inhibiting or alleviating the oxidative stress response.

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備注/Memo

備注/Memo:
基金項目:第四批全國中醫(yī)優(yōu)秀人才研修項目(國中醫(yī)藥人教發(fā)〔2017〕24號)
通訊作者:李西海 E-mail:[email protected]
更新日期/Last Update: 2020-12-20