|
| 基于网络药理学探讨骨碎补抗骨质疏松的分子作用机制 |
| Exploration into molecular mechanism of Drynariae Rhizoma for the treatment of osteoporosis based on network pharmacology |
| |
| DOI：10.3969/j.issn.1006-7108.2019.08.006 |
| 中文关键词: 中医中药 骨碎补 骨质疏松 网络药理学 生物过程 信号通路 |
| 英文关键词:Rhizoma Drynariae osteoporosis network pharmacology biological process KEGG pathway |
| 基金项目:国家自然基金（81774339）；国家自然基金青年项目（81603641）；广东省科技项目（2017A020213030）. |
|
| 摘要点击次数: 1739 |
| 全文下载次数: 505 |
| 中文摘要: |
| 目的 构建骨碎补活性成分-作用靶点网络和蛋白相互作用网络，分析靶点涉及的生物过程和通路，研究骨碎补抗骨质疏松（osteoporosis，OP）的潜在机制。方法 通过TCMSP数据库筛选骨碎补的活性成分，用Swiss数据库预测其靶点，与Disgenet数据库获得的OP靶点相映射，得到骨碎补抗OP的潜在靶点。利用Cytoscape构建“骨碎补-活性化合物-潜在靶点”网络，采用String数据库和Cytoscape构建蛋白相互作用网。利用David数据库进行GO生物功能和KEGG通路富集分析。结果 得到骨碎补活性成分18个，其治疗OP的潜在靶点24个。成分豆甾醇（stigmasterol）、β-谷甾醇（beta-sitosterol）、黄烷酮（Eriodyctiol (flavanone)）、山奈酚（kaempferol）、柚皮素（naringenin）、圣草酚（eriodictyol）和环木菠萝烷醇（cycloartenone）能与5个以上靶点相连，为骨碎补抗OP的主要成分。靶点CYP19A1与成分连接次数为8次，对骨碎补抗OP具有重要意义； CYP1B1为4次，MMP1、CA2、CYP17A1、ESR1、MMP13、LDLR、CYP1A1、MMP2均为3次，对骨碎补抗OP有较大意义。GO生物过程和KEGG富集分析显示，骨碎补抗OP主要涉及氧化还原过程（oxidation-reduction process）、基因表达正调控（positive regulation of gene expression）、类固醇代谢）steroid metabolic process）、RNA聚合酶Ⅱ启动子的转录起始（transcription initiation from RNA polymerase II promoter）等生物学过程，通过调节代谢通路（Metabolic pathways）、类固醇激素生物合成（Steroid hormone biosynthesis）、卵巢类固醇生成（Ovarian steroidogenesis）、癌症通路（Pathways in cancer）等通路发挥抗OP作用。结论 本研究体现骨碎补多成分、多靶点、多途径的作用特点，为阐释其治疗OP的作用机制提供了科学依据，为进一步开展骨碎补抗OP分子作用机制的研究以及新药开发等提供了新思路和新方法。 |
| 英文摘要: |
| Objective To explore the molecular mechanism of Drynariae Rhizoma for treating osteoporosis by constructing the active ingredients-targets network and protein interactions network. In this network the biological process and relevant pathways of key targets were analysed. Methods The main active ingredients of Drynariae Rhizoma were screened by TCMSP with limitation index and targets were predicted through Swiss database. After Mapping the targets of Drynariae Rhizoma to the OP disease targets obtained from the Disgenet database, the key targets for the treatment of OP were obtained. Cytoscape software was used to construct the active components- potential targets network of Drynariae Rhizoma. The protein interactions network was constructed by using String database and Cytoscape software. GO- biological process and KEGG pathways of the key targets were analyzed by DAVID. Results Eighteen active ingredients and twenty four key targets of Rhizoma Drynariae for OP treatment were screened. Among the active ingredients, Stigmasterol, beta-sitosterol, Eriodyctiol (flavanone), kaempferol, naringenin, eriodictyol and cycloartenone can link to more than five targets, suggesting that they might be the main active ingredient of Rhizoma Drynariae in treating OP. The number of connections between target CYP19A1 and the component is 8 times, which is of great significance for Rhizoma Drynariae in treating OP; CYP1B1 was 4 times, and MMP1, CA2, CYP17A1, ESR1, MMP13, LDLR, CYP1A1 and MMP2 were all 3 times, indicating that they have great significance for Rhizoma Drynariae in treating OP. GO- biological process and KEGG pathways enrichment analysis showed that the mechanisms with Rhizoma Drynariae in treating OP mainly involves oxidation-reduction process, positive regulation of gene expression, steroid metabolic process, transcription initiation from RNA polymerase II promoter, regulation of metabolic pathways, steroid hormone biosynthesis, ovarian steroidogenesis, pathways in cancer and other signaling pathways to play its anti-osteoporosis effect. Conclusion This study shows the multi-component, multi-target and multi-pathway characteristics of Rhizoma Drynariae, providing a scientific basis for explaining its mechanism of action in treating OP, as well as, new ideas and clues for further research on the mechanisms of the anti-osteoporosis effects of Rhizoma Drynariae. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|