基于网络药理学的“丹参-红花药对”抗骨质疏松分子机制研究  

Analysis of Anti-osteoporosis Molecular Mechanism of Herbal Pair Danshen and Honghua Based on Network Pharmacology

作　　者：张罡瑜 何琪 林瑞婷 温晓雯 杨均政 钟莎 曾嘉旭 王海彬[2,3] 陈鹏[2,3] Zhang Gangyu;He Qi;Lin Ruiting(The First Clinical Medical College,Chinese Medicine of Lingnan Medical Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The Lab of Orthopaedics and Traumatology,Chinese Medicine of Lingnan Medical Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Joint Orthopedics De partment,the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]广州中医药大学第一临床医学院,广州510405 [2]广州中医药大学岭南医学研究中心中医骨伤科实验室,广州510405 [3]广州中医药大学第一附属医院关节骨科,广州510405

出　　处：《华中科技大学学报（医学版）》2021年第3期284-291,319,共9页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81774339);国家自然科学基金青年基金资助项目(No.81603641)。

摘　　要：目的构建丹参-红花药对活性成分-作用靶点网络和蛋白相互作用网络,分析靶点涉及的生物学过程和通路,研究丹参-红花抗骨质疏松(osteoporosis,OP)的分子作用机制。方法通过TCMSP数据库筛选丹参-红花药对的潜在活性成分,用Swiss数据库预测其作用靶点,与Disgenet数据库获得的OP靶点相映射,得到丹参-红花药对抗OP的潜在靶点。采用Cytoscape软件构建"药物-活性成分-潜在靶点"网络,利用String数据库和Cytoscape构建蛋白质相互作用网络。使用David数据库对丹参-红花药对的作用靶点进行GO生物功能分析和KEGG通路富集分析。结果获得丹参和红花中具有类药性、口服吸收良好的潜在活性成分分别为65个和22个,其治疗OP的潜在靶点36个。其中成分Poriferast-5-en-3beta-ol、Poriferasterol、Flavoxanthin、Beta-sitosterol、Stigmasterol、Luteolin、Kaempferol、α-amyrin、5,6-dihydroxy-7-isopropyl-1,1-dimethyl-2,3-dihydrophenanthren-4-one、Przewalskin a、Salviolone、Phytoene、Phytofluene、Beta-carotene等能与5个及5个以上的靶点相连接,为丹参-红花药对治疗OP的主要活性成分。蛋白质网络分析显示,靶点基因ESR1、MAPK3、ERBB2、CYP19A1、CYP2B6的Degree值均大于中位数7的2倍以上。GO生物过程分析和KEGG通路富集分析显示,丹参-红花药对治疗OP主要涉及的生物过程有妊娠期乳腺分支、转录后基因沉默的负调控、RNA对基因沉默的负调控、前列腺生长、乳腺导管形态形成分支、花生四烯酸的代谢等过程,主要富集的通路为卵巢类固醇生成、甾类激素生物合成、催乳素信号通路、粘着连接、膀胱癌、雌激素信号通路等,表明丹参-红花可以通过参与调控多种生物学过程发挥治疗OP的作用。结论丹参-红花药对治疗OP具有多成分、多靶点、多途径的作用特点,该研究为进一步开展丹参-红花药对抗OP分子作用机制的研究以及新药开发等提供了新思路和Objective To construct the active ingredients and their potential targets and protein interaction network of the herbal pair Danshen(Salvia miltiorrhiza)and Honghua(Carthamus tinctorius L),analyze the biological processes and pathways involved in the target,and study the anti-osteoporosis molecular mechanism of the herbal pair Danshen and Honghua.Methods By using the traditional Chinese medicine system pharmacology platform(TCMSP),the potential active ingredient of the herb pair Danshen and Honghua was screened,and then the targets was predicted by Swiss database to obtain potential target to treat OP.Cytoscape software was used to construct the network of"drug-active ingredient-potential target",and David database was used to analyze the GO biological function and KEGG pathway enrichment of the target of Danshen and Honghua.Based on the above methods,the action mechanism of Danshen and Honghua in treating OP was explored.Results There were 65 potential active ingredients with drug-likeness and good absorption by oral administration.There were 36 potential targets among these.The main active ingredients could be connected to 5 or more targets,such as Poriferast-5-en-3 beta-ol,Poriferasterol,Flavoxanthin,Beta-sitosterol,Stigmasterol,Luteolin,Kaempferolα-amyri,5,6-dihydroxy-7-isopropyl-1,1-dimethyl-2,3-dihydrophenanthren-4-one,Przewalskin a,Salviolone,Phytoene,Phytofluene,Beta-carotene.The analysis of the protein network showed that the degree values of ESR1,MAPK3,ERBB2,CYP19A1 and CYP2B6 were more than twice the median of 7,which indicates that it has great significance for the treatment of OP.The GO biological function and KEGG pathway enrichment showed that there were many major related biological processes like mammary gland branching involved in pregnancy,negative regulation of posttranscriptional gene silencing,negative regulation of gene silencing by RNA,prostate gland development,branching involved in mammary gland duct morphogenesis,arachidonic and metabolic process.The main enrichment pathways showed tha

关 键 词：丹参-红花药对 骨质疏松 网络药理学 生物过程 信号通路 

分 类 号：R681.4[医药卫生—骨科学]