| 周雅,汪琪,孙庆珠,等.白术-白芍药对防治肝纤维化的网络药理学研究[J].浙江中医药大学学报,2021,45(9):1033-1041. |
| 白术-白芍药对防治肝纤维化的网络药理学研究 |
| The Treatment Mechanism of Atractylodes Macrocephala Koidz and Radix Paeoniae Alba Herb Pairs on Hepatic Fibrosis by Network Pharmacology |
| DOI：10.16466/j.issn1005-5509.2021.09.018 |
| 中文关键词: 白术 白芍 肝纤维化 网络药理学 靶点基因 作用机制 富集分析 信号通路 |
| 英文关键词: Atractylodes macrocephala Koidz Radix Paeoniae Alba liver fibrosis network pharmacology target genes functional mechanism feature enrichment signaling pathway |
| 基金项目:国家自然科学基金项目(81573700)；浙江省自然科学基金项目(LY16H280004) |
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| 中文摘要: |
| [目的]运用网络药理学方法分析白术-白芍药对治疗肝纤维化的有效活性成分，预测其作用靶点，并分析其可能的作用机制，为肝脾同治理论提供网络药理学依据。[方法]利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)筛选白术-白芍药对的活性成分及其对应靶点，结合人类基因组注释数据库(Human Genome Annotation Database，GeneCards)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man，OMIM)数据库筛选治疗肝纤维化的潜在作用靶点。利用网站Venny 2.1.0绘制韦恩图，然后通过Cytoscape 3.7.2软件和String数据库构建成分-靶点-疾病网络图和靶点间的蛋白互作(protein-protein interaction，PPI)网络，通过Metoscape平台对靶点进行基因本体(gene ontology，GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路与基因功能富集分析。[结果]经过筛选，共获得白术-白芍的 20个有效药物成分，与肝纤维化相关的关键化学成分9个，药对-肝纤维化的共同靶点53个，PPI关键靶点11个，蛋白激酶B1(protein kinase B1，AKT1)、白细胞介素-6(interleukin-6，IL-6)、丝裂原激活蛋白激酶8(mitogen activated protein kinase 8，MAPK8)、肿瘤坏死因子(tumor necrosis factor，TNF)是白术-白芍作用的关键靶点。GO富集分析结果包括生物过程(biological process，BP)条目20条、细胞组分(celluar component，CC)11条、分子功能(molecular function，MF)18条；KEGG富集分析发现相关信号通路18条，涉及糖尿病并发症中的晚期糖基化终末产物-糖基化终末产物受体(advanced glycosylation end product-receptor of advanced glycosylation end product，AGE-RAGE)信号通路、癌症信号通路、流体剪切应力和动脉粥样硬化通路、核因子-κB(nuclear factor-κB，NF-κB)信号通路、铂剂耐药通路、大肠癌通路、小细胞肺癌通路、肝细胞癌通路等。[结论]白术-白芍药对治疗肝纤维化具有多组分、多靶点、多途径的调控特点，本研究为深入探索肝纤维化的防治提供了新的思路。 |
| 英文摘要: |
| [Objective] To analyze the active components of Atractylodes macrocephala Koidz-Radix Paeoniae Alba in the treatment of liver fibrosis by network pharmacology， predict its action target and analyze its possible effective mechanism， so as to provide the basis of network pharmacology for the theory of simultaneous treatment of the liver and spleen. [Methods] The active components and corresponding targets of Atractylodes macrocephala Koidz and Radix Paeoniae Alba were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)， and the potential targets for the treatment of liver fibrosis were screened by the Human Genome Annotation Database(GeneCards) and Online Mendelian Inheritance in Man(OMIM) database. The Venny diagram was drawn by Venny 2.1.0， and then the component-target-disease network diagram and protein-protein interaction(PPI) network between targets were constructed by Cytoscape 3.7.2 software and String database.And gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway and gene function enrichment analysis were performed on the targets through Metoscape platform.[Results]Through screening， 20 effective chemical components of Atractylodes macrocephala Koidz and Radix Paeoniae Alba， 9 key chemical components related to liver fibrosis， 53 common targets of drug pair-liver fibrosis，and 11 key targets of PPI were obtained. The protein kinase B1(AKT1)， interleukin-6(IL-6)， mitogen activated protein kinase 8(MAPK8) and tumor necrosis factor(TNF) are the key targets of Atractylodes macrocephala Koidz-Radix Paeoniae Alba.The results of GO enrichment analysis included 20 biological processes(BP)， 11 cellular components(CC) and 18 molecular functions(MF); KEGG enrichment analysis obtained 18 related signaling pathways，involving advanced glycosylation end product-receptor of advanced glycosylation end product(AGE-RAGE) signaling pathway in diabetic complications， pathways in cancer， fluid shear stress and atherosclerosis pathway， nuclear factor-κB(NF-κB) signaling pathway， platinum drug-resistance pathway，colorectal cancer pathway， small cell lung cancer pathway， hepatocellular carcinoma pathway. [Conclusion]Atractylodes macrocephala Koidz-Radix Paeoniae Alba have the characteristics of multi-component， multi-target and multi-channel regulation in the treatment of liver fibrosis. This study provides a new way for further exploring the prevention and treatment of liver fibrosis. |
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