[1]谭雪,许云腾,王圣杰,等.基于网络药理学方法探讨二至丸治疗骨质疏松症的有效成分、作用靶点及作用机制[J].中医正骨,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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基于网络药理学方法探讨二至丸治疗骨质疏松症的有效成分、作用靶点及作用机制()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第32卷
期数:
2020年12期
页码:
1-10
栏目:
基础研究
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:
谭雪1; 许云腾1; 王圣杰1; 王丽丽1; 付长龙2; 叶锦霞1; 郑春松1; 叶蕻芝2; 李西海2
(1.福建中医药大学中西医结合研究院,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):
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
关键词:
骨质疏松;  二至丸;  网络药理学
Keywords:
osteoporosis;  Erzhi Pill;  network pharmacology
摘要:
目的:探讨二至丸治疗骨质疏松症(osteoporosis,OP)的有效成分、作用靶点及作用机制。方法:在GEO数据库检索OP相关基因,同时在中药系统药理学数据库及分析平台检索二至丸的组成中药(女贞子、墨旱莲)的有效成分和药物靶点。利用PERL软件将检索到的OP相关基因与二至丸的药物靶点取交集,初步获得二至丸治疗OP的靶点。在此基础上利用Cytoscape软件建立二至丸治疗OP的有效成分-靶点网络进行分析,并利用R软件进行靶点基因GO功能富集分析和KEGG通路富集分析。最后使用PERL软件筛选出KEGG富集分析表达位于前20的信号通路和对应的靶点基因,利用Cytoscape软件构建二至丸治疗OP的信号通路-靶点关系网络进行分析。结果:在GEO数据库中筛选出2个与OP相关的基因芯片,分别为GSE35956和GSE56116,其共同的OP相关基因102个、共同上调基因34个、共同下调基因17个。利用PERL软件将2个芯片中的OP相关基因与二至丸的药物靶点取交集,共筛选出二至丸治疗OP的42个靶点,其中芯片GSE35956对应的靶点28个、芯片GSE56116对应的靶点16个。2个芯片对应的有效成分-靶点网络中,存在7个共同有效成分,分别为紫铆素、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个共同靶点,分别为谷胱甘肽s-转移酶mu1(glutathione S-transferase mu1,GSTM1)和GSTM2。靶点基因GO功能分析显示,靶点基因的分子功能主要包括谷胱甘肽结合、寡肽结合、谷胱甘肽转移酶活性、与修饰的氨基酸结合。靶点基因KEGG富集分析及信号通路-靶点关系网络显示,二至丸治疗OP的主要靶点基因包括CDKN1A、CHUK、MYC、RELA、GSTM1、GSTM2、FOS、IL4、CD40LG,其中CDKN1A、GSTM1、GSTM2、RELA、MYC、FOS是上调基因,CHUK、CD40LG、IL4是下调基因; 2个芯片中共同的靶点基因为GSTM1和GSTM2,且在2个芯片中都属于上调基因; 二至丸治疗OP的主要信号通路为与感染、心血管疾病、癌症、代谢、免疫相关的信号通路。结论:二至丸治疗OP的有效成分主要为黄酮类化合物,主要靶点为GSTM1和GSTM2,其作用机制可能是通过抑制或减轻氧化应激反应发挥治疗作用。
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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备注/Memo

备注/Memo:
基金项目:第四批全国中医优秀人才研修项目(国中医药人教发〔2017〕24号)
通讯作者:李西海 E-mail:lixihaifz@163.com
更新日期/Last Update: 2020-12-20