摘要
目的:探讨华虎内攻汤治疗垂体腺瘤的有效成分、靶点及其潜在的分子机制。方法:利用TCMSP数据库筛选华虎内攻汤的活性成分及靶点蛋白,通过OMIM和Gene-Cards数据库获得垂体腺瘤靶点,使用韦恩工具来识别华虎内攻汤活性成分和垂体腺瘤之间的交集靶点,将交集靶点导入STRING构建蛋白质-蛋白质相互作用(Protein-Protein Interaction,PPI)网络,再将数据导入Cytoscape软件中进行分析,得到关键基因,并取前十位构建活性成分-靶点网络图。运用Metascape数据库进行基因本体(Gene Ontology,GO)和基因百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,最后运用Autodock进行分子对接验证。结果:获得华虎内攻汤活性成分276个,相关靶点1 206个,获得1 137个垂体腺瘤相关靶点,得到交集靶点239个。对交集靶点进行PPI网络分析,获得前十位核心作用靶点(TP53、GAPDH、Akt1等);通过前十位核心靶点与活性成分作活性成分-靶点网络图,筛选出最相关的活性成分11个,KEGG富集分析显示,这些靶点可能通过PI3K-Akt信号通路、P53信号通路等10条信号通路进行调节;GO富集分析表明,汤剂可能通过调节激素水平、细胞增殖等影响生物过程,影响受体复合物、蛋白激酶复合物的细胞组分,调节蛋白激酶活性、与p53结合等分子功能;最后结合KEGG富集通路及PPI网络,选择TP53靶蛋白与活性成分embinin分子对接,结合能为-5.28 kcal/mol,通过ASN、GLY、GLU 3个氨基酸残基相连接。结论:华虎内攻汤可能通过调节TP53、Akt1、STAT3等靶点,调控P53信号通路、PIK3-Akt信号通路、JAK-STAT信号通路对垂体腺瘤产生作用。
Objective:To explore the active components,targets,and potential molecular mechanisms of Hua-Hu-Nei-gong Decoction in the treatment of pituitary adenomas.Methods:Active components and target proteins of Hua-Hu-Nei-gong Decoction were screened using the TCMSP database.Pituitary adenoma targets were obtained from the OMIM and GeneCards databases.Venn tools were used to identify intersecting targets between Hua-Hu-Nei-gong Decoction's active components and pituitary adenomas.The intersecting targets were imported into STRING to construct a PPI network.The data was further analyzed using Cytoscape software to identify key genes,and the top ten genes were used to construct an active component-target network.GO and KEGG enrichment analyses were conducted using the Metascape database and finally molecular docking validation using Autodock.Results:A total of 276 active components and 1206 related targets were identified for Hua-Hu-Nei-gong Decoction,along with 1137 pituitary adenoma-related targets,yielding 239 intersecting targets.PPI network analysis of these intersecting targets revealed the top ten core targets(TP53,GAPDH,Akt1,etc).An active component-target network was created using the top ten core targets,identifying the 11 most relevant active components.KEGG enrichment analysis indicated that these targets might regulate the PI3K-Akt signaling pathway,P53 signaling pathway,and other pathways.GO enrichment analysis suggested that the decoction might influence biological processes by regulating hormone levels and cell proliferation,affecting cellular components of receptor complexes and protein kinase complexes,and regulating molecular functions suchas protein kinase activity and binding to p53.Finally,combining KEGG enrichment pathways and the PPI network,TP53 was selected for molecular docking with the active component embinin,showing a binding energy of-5.28 kcal/mol and interactions involving ASN,GLY,and GLU amino acid residues.Conclusion:Hua-Hu-Nei-gong Decoction may exert its effects on pituitary adenomas by regulating targets such as TP53,Akt1,and STAT3,and modulating the P53 signaling pathway,PI3K-Akt signaling pathway,and JAK-STAT signaling pathway.
作者
渠羽飞
刘祺
QU Yufei;LIU Qi(Shihezi University School of Medicine,Shihezi,Xinjiang 832002,China;Department of Neurosurgery,the First Affiliated Hospital of Shihezi University,Shihezi,Xinjiang 832008,China)
出处
《农垦医学》
2025年第3期231-236,共6页
Journal of Nongken Medicine
关键词
垂体腺瘤
网络药理学
华虎内攻汤
分子对接
Pituitary adenoma
Network pharmacology
Hua-hu-nei-gong decoction
Molecular docking
