| 摘要: |
| 目的:通过网络药理学和分子对接技术探讨知柏地黄丸治疗特发性中枢性性早熟(ICPP)的作用机制。方法:基于中药
系统药理学数据库与分析平台(TCMSP)和文献研究挖掘知柏地黄丸中各个药物的活性成分,并利用TCMSP 数据库预测活性
成分作用靶点,通过全球蛋白质资源(UniProt)数据库对靶点蛋白进行校正。在GeneCards、在线孟德尔遗传(OMIM)、DisGeNET
数据库中获得ICPP 的疾病靶点。取药物靶点和疾病靶点的交集靶点并制作韦恩图,运用Cytoscape 3. 9. 1 软件制作“中药-活性
成分-靶点”网络并进行网络拓扑分析获取中药核心成分,利用STRING 数据库构建蛋白互作网络并导入Cytoscape 3. 9. 1 软件
中筛选出核心靶点。利用DAVID 数据库对交集靶点进行基因本体( GO) 和京都基因与基因组百科全书( KEGG) 分析;利用
AutoDockTools 和AutoDock Vina 脚本将得到的核心成分和核心靶点进行分子对接。结果:筛选得到知柏地黄丸复方中活性成
分114 个,相关靶点233 个,ICPP 疾病靶点1 628 个,交集靶点111 个。复方核心成分包括槲皮素、山奈酚、β-谷甾醇、脱水淫羊藿
素、豆甾醇等22 个,核心靶点包括AKT1、FOS、ESR1、IL6、EGFR 等14 个。GO 分析结果显示,交集靶点与基因表达的正向调节、
DNA 诱导转录的正向调节、RNA 聚合酶2 启动子转录正调节、突触后膜的组成、蛋白激酶结合等相关,KEGG 分析结果主要涉及到
AGE-RAGE 信号通路、癌症通路、内分泌抵抗、细胞衰老等信号通路。分子对接结果显示,核心成分与靶点具有较好的结合活性。
结论:知柏地黄丸治疗ICPP 具有多成分、多靶点、多通路的特点,为进一步研究知柏地黄丸治疗ICPP 的作用机制奠定了基础。 |
| 关键词: 知柏地黄丸 特发性中枢性性早熟 网络药理学 半柔性分子对接 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2024.04.009 |
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| 基金项目:北京中医药大学一流学科建设中医儿科学科项目,编号90070161020004。 |
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| Mechanism of Zhibai Dihuang Pills in the Treatment of Idiopathic Central Precocious Puberty Based onNetwork Pharmacology and Molecular Docking Technology |
| Luo Yuwei, Ma Xiaojing, Qu Manjiao, Zhang Tianjiao, Liu Yuqing |
| ((Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China)) |
| Abstract: |
| Objective: To explore the mechanism of Zhibai Dihuang pills in the treatment of idiopathic central precocious puberty
(ICPP) based on network pharmacology and molecular docking technology. Methods: Based on literature research and retrieval of
Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform ( TCMSP), the active components of Zhibai
Dihuang pills were obtained. TCMSP database was used to predict the target of active components, and the target protein was calibrated
by the UniProt database. GeneCards, Online Mendelian Inheritance in Man (OMIM) and DisGeNET databases were used to obtain
ICPP related target genes. Intersection targets of drug targets and disease targets were obtained to make Venn diagram. Cytoscape 3. 9. 1
was used to construct the “drug-active components-targets” network and perform topological analysis to obtain core components of
traditional Chinese medicine. STRING database was used to construct the protein-protein interaction network and screen out the key
targets. Intersection targets were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) by using DAVID
database. AutoDockTools and AutoDock Vina scripts were used to obtained core components and core targets for molecular docking.
Results: A total of 114 active components of Zhibai Dihuang pills and 233 related potential targets were screened out, with 1,628 ICPP
related target genes and 111 intersection targets. The 22 core components mainly included quercetin, kaempferol, β-sitosterol, icariin and
stigasterol, and the 14 core targets mainly included AKT1, FOS, ESR1, IL6 and EGFR. GO analysis results showed that intersection
targets were associated with positive regulation of gene expression, positive regulation of DNA-induced transcription, positive regulation of
RNA polymerase 2 promoter transcription, postsynaptic membrane composition and protein kinase binding. KEGG analysis mainly involved
signaling pathways such as advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE) signaling pathway,
cancer pathway, endocrine resistance,and cellular senescence. Molecular docking results showed that the core components had good
binding activity to the targets. Conclusion: Zhibai Dihuang pills has multi-component, multi-target and multi-pathway characteristics in the
treatment of ICPP, which lays foundation for further research on the mechanism of Zhibai Dihuang pills in the treatment of ICPP. |
| Key words: Zhibai Dihuang pills idiopathic central precocious puberty network pharmacology semi flexible molecular docking |
