基于网络药理学与分子对接技术探讨四氢姜黄素对肝细胞癌作用的分子机制  

Molecular mechanism of tetrahydrocurcumin in hepatocellular carcinoma based on network pharmacology and molecular docking

作　　者：包卓聪 王庆庆 贾辉 陆瑶 时娜 张艳 Bao Zhuocong;Wang Qingqing;Jia Hui;Lu Yao;Shi Na;Zhang Yan(Shenyang Medical College Graduate School,Shenyang 110034,China;Shenyang Medical College of Oral Medicine,Shenyang 110034,China;Shenyang Medical College,Faculty of Traditional Chinese Medicine,Shenyang 110034,China;Key Laboratory for the Study of Human Population Specificity and Important Disease Phenotypes in Liaoning Province,Shenyang 110034,China;School of International Education,Shenyang Medical College,Shenyang 10034,China)

机构地区：[1]沈阳医学院研究生院,辽宁沈阳110034 [2]沈阳医学院口腔医学院,辽宁沈阳110034 [3]沈阳医学院中医药学院,辽宁沈阳110034 [4]辽宁省人类族群特异性及重要疾病表型组学研究重点实验室,辽宁沈阳110034 [5]沈阳医学院国际教育学院,辽宁沈阳110034

出　　处：《实用药物与临床》2023年第10期877-883,共7页Practical Pharmacy and Clinical Remedies

基　　金：辽宁省教育厅科学研究项目;沈阳医学院科技基金项目(20171004);沈阳医学院硕士研究生科技创新基金项目(Y20220509)。

摘　　要：目的 通过网络药理学靶点预测方法结合分子对接技术,探讨四氢姜黄素抗肝细胞癌(HCC)的作用机制。方法 从多个数据库中获得四氢姜黄素或HCC潜在作用靶点;通过在线富集分析平台Metascape,将核心靶点进行GO功能和KEGG通路富集分析以及可视化处理,了解四氢姜黄素治疗肝细胞癌可能涉及的生物过程与信号通路;采用SYBYL2.0软件进行半柔性分子对接实验,以验证药物分子与其核心靶点的结合活性。结果 四氢姜黄素与HCC共同靶点77个;核心靶点共16个,包括TP53、EGFR、PIK3CA等;潜在作用靶点KEGG分析的97条通路包括PI3K-AKT信号通路、HIF-1信号通路等。GO富集分析表明,四氢姜黄素参与细胞对化学压力的反应、细胞对氧含量降低的反应等。分子对接结果显示,四氢姜黄素与多个疾病关键靶点具有较高的结合能力,对接评分较高的为四氢姜黄素与PIK3CA靶点蛋白。结论 四氢姜黄素能够通过多靶点、多通路达到治疗肝细胞癌的目的,本研究为进一步研究四氢姜黄素抗肝细胞癌的作用机制提供了参考。Objective To explore the mechanism of action of tetrahydrocurcumin(THC)against hepatocellular carcinoma(HCC)through a combination of network pharmacological targeting prediction and molecular docking.Methods Potential action targets of THC or HCC were obtained from multiple databases.To understand the potential biological processes and signaling pathways involved in the treatment of HCC with THC,core targets were enriched for GO function and KEGG pathway,as well as visualization via the online enrichment analysis platform Metascape.Semi-flexible molecular docking was performed using SYBYL 2.0 software to validate the binding activity of drug molecules to core targets.Results There were 77 co-targets of THC and HCC.Sixteen core targets included TP53,EGFR,PIK3CA,etc.The 97 pathways analyzed for potential target KEGG included PI3K-AKT signaling pathway and HIF-1 signaling pathway.GO enrichment analysis showed that THC was involved in cell responses to chemical stress and cell responses to reduced oxygen levels.Molecular docking showed high binding ability of THC to multiple disease-critical targets,with high docking scores for THC and PIK3CA target proteins.Conclusion THC can be used in the treatment of HCC through multiple targets and pathways,providing a reference for further investigation in the mechanism of action of THC against HCC.

关 键 词：肝细胞癌 四氢姜黄素 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]