基于GEO数据库结合网络药理学及分子对接逆向挖掘干预肝癌的中药

doi:10.3976/j.issn.1002-4026.20230082

摘要/Abstract

摘要：

基于GEO(gene expression omnibus)数据库结合网络药理学及分子对接,从分子水平逆向挖掘具有抗肝癌活性的中药。通过GEO、GeneCards、OMIM和TTD等疾病靶点数据库获取肝癌的重要靶点。利用STRING平台获取核心靶点,结合TCMIP(integrative pharmacology-based research platform of traditonal Chinese medicine)和TCMID(traditional Chinese medicine integraive database)数据库筛选核心成分,采用TCMSP(traditonal Chinese medicine system pharmacology database and analysis platform)数据库筛选核心中药,通过分子对接和细胞实验验证筛选结果。从疾病靶点数据库得到398个肝癌的重要靶点,进一步筛选出8个核心靶点、11个核心成分和1味核心中药葛根;分子对接结果表明葛根的3个核心成分(槲皮素、黄岑素、豆甾醇)可以与部分核心靶点(CDK1、CDC20)自发地结合;细胞实验结果表明葛根提取物可以有效抑制肝癌细胞HepG2的增殖。该结果可以为葛根的研究与开发提供参考,为葛根抗肝癌活性成分的挖掘提供理论依据。

关键词: 葛根, 抗肝癌活性成分, 网络药理学, 分子对接, GEO数据库

Abstract:

Based on the gene expression omnibus(GEO) database, combined with network pharmacology and molecular docking technology, we aimed to conduct reverse network pharmacology research from a molecular level to identify Chinese medicine with anti-hepatocellular carcinoma (HCC) activity. Relevant targets of HCC were acquired from databases including GEO, GeneCards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The core targets were identified using the String platform, and the core constituents were screened from the TCMIP(integrative pharmacology-based research platform of traditonal Chinese medicine) and TCMID(traditional Chinese medicine integraive database) databases. The core traditional Chinese medicine (TCM) was ultimately selected through the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP). Molecular docking technology and cellular experiments were employed to identify relevant screening results. A total of 398 important targets for HCC were found from the disease target databases, from which 8 core targets, 11 core constituents, and 1 core TCM (Puerariae Lobatae Radix) were further screened. Molecular docking results showed that three core constituents (quercetin, genistein, and coumestrol) from kudzu root could spontaneously bind with some core targets (CDK1 and CDC20), and cell experiments demonstrated that the extract from Puerariae Lobatae Radix could effectively inhibit the proliferation of HepG2 liver cancer cells. This study may provide a reference for the research and development of Puerariae Lobatae Radix and offer a theoretical basis for the discovery of its anti-HCC active ingredients.

Key words: Puerariae Lobatae Radix, antiliver cancer activity, network pharmacology, molecular docking, gene expression omnibus

中图分类号:

R285

魏泽坤, 杨雨洁, 刘双, 王燕, 董红敬, 刘春梅. 基于GEO数据库结合网络药理学及分子对接逆向挖掘干预肝癌的中药[J]. 山东科学, 2024, 37(3): 39-47.

WEI Zekun, YANG Yujie, LIU Shuang, WANG Yan, DONG Hongjing, LIU Chunmei. Reverse mining of Chinese medicine for intervention of liver cancer based on GEO database combined with network pharmacology and molecular docking technology[J]. Shandong Science, 2024, 37(3): 39-47.

图/表 5

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化学成分	核心靶点蛋白结合能/(kJ·mol^-1)
化学成分	CDK1	CDC20
黄岑素	—	-12.099 9
豆甾醇	-20.892 1	—
槲皮素	-14.988 7	—