基于网络药理学探讨银杏叶抗肝癌的作用机制

To explore the mechanism of ginkgo folium against liver cancer based on network pharmacology

目的:基于网络药理学及分子对接方法探讨银杏叶治疗肝癌的活性成分、潜在靶点及作用机制。方法:采用TCMSP、Swiss Target Prediction、DrugBank和Genecards等数据库预测银杏叶的活性成分和肝癌相关疾病靶点,取交集后构建蛋白互作网络,使用String、Cytoscape3.9.1分析平台绘制“成分-疾病-靶点”PPI网络图,采用Metascape分析平台对核心靶点进行GO功能和KEGG通路富集分析,使用Chem BIO 3D和Auto Dock Tools进行分子对接,模拟化合物与疾病靶点间的结合活性。结果:银杏叶活性成分27种主要为黄酮类化合物,关联861个疾病靶点,肝癌疾病靶点1637个,78个银杏叶与肝癌交集靶点,可能通路10条,包括Proteoglycans in cancer、Endocrine resistance、Estrogen signaling pathway等;分子对接结果表明活性化合物与靶点亲和力较好。结论:银杏叶中木犀草素-4'-葡萄糖苷、毛茛黄素、香叶木素等可能是治疗肝癌的关键成分,体现了银杏叶多成分、多靶点治疗肝癌的特点,为今后银杏叶的深度研究与开发提供了参考思路。

Objective:To investigate the active ingredients,potential targets and mechanism of action of Ginkgo biloba in the treatment of hepatocellular carcinoma based on network pharmacology and molecular docking method.Methods:Using TCMSP,Swiss Target Prediction,DrugBank and Genecards databases to predict the active components of Ginkgo Folium and hepatocellular carcinoma related disease targets,the protein interaction network was constructed after the intersection,String and Cytoscape3.9.1 analysis platforms were used to map the PPI network of“composition-disease-target”,Metascape analysis platform was used to conduct GO function and KEGG pathway enrichment analysis for core targets,and Chem BIO 3D and Auto Dock Tools were used for molecular docking.The binding activity between the compound and the disease target was simulated.Results:The 27 active components of Ginkgo Folium were screened out,which was mainly flavonoids,and associated with 861 disease targets,1637 disease targets of liver cancer,and 78 intersection targets of ginkgo Folium and liver cancer.There were 10 possible pathways including Proteoglycans in cancer,Endocrine resistance,Estrogen signaling pathway,etc.The results of molecular docking showed that the affinity between the active compound and the target was good.Conclusion:Luteolin-4'-glucoside,Flavoxanthin,Diosmetin in Ginkgo Folium may be the key components in the treatment of liver cancer,it reflect the depth of ginkgo Folium multi-component and multi-target treatment characteristics of liver cancer,which provides a reference idea for in-depth research on development of Ginkgo Folium.