摘要
目的本研究目的是通过网络药理学及分子对接方法探寻龙葵-肿节风药对治疗胃癌的作用机制。方法通过TCMSP数据库收集龙葵-肿节风药对活性成分;在TTD、DrugBank、Pharmgkb等疾病靶点数据库搜索汇总出胃癌基因靶点。利用Cytoscape软件构建“龙葵-肿节风药对活性成分—胃癌交集靶点”关系网络图。使用String数据库构建靶点蛋白相互作用网络(PPI)并用Cytoscape软件筛选出得出核心靶点。同时利用基因本体(GO)和京都基因与基因组百科全书(KEGG)富集从宏观角度分析核心靶点,并通过Autodock软件进行分子对接验证主要成分-核心靶点结合活性。结果我们确定了龙葵-肿节风药对主要的药物活性成分主要是槲皮素和β-谷甾醇;核心靶点分别为AKT1、TNF、IL6、TP53和IL1B。KEGG富集分析表明,PI3K-Akt信号通路及炎症相关信号通路可能是重要的通路。GO分析提示主要涉及的生物过程包括对激素的反应、细胞对氮化合物的反应、对异生刺激的反应等;参与的分子功能包括转录因子结合、蛋白质均二聚活性、蛋白质结构域特异性结合等;涉及的细胞组分主要是膜筏、转录调节复合体、质膜蛋白复合物等。分子对接结果表明,主要活性与核心靶点具有良好的结合活性。结论研究表明,龙葵-肿节风药对可能主要通过作用于AKT1、TNF、IL6、TP53和IL1B等靶点,进而调控PI3K-Akt通路、炎症等相关通路,从多靶点、多通路发挥治疗胃癌的作用。本研究为后续开展龙葵-肿节风药对抗胃癌的体内外实验研究奠定了基础。
Objective The purpose of this study is to explore the mechanism of Solanum nigrum-Herba Sarcandrae(LK-ZJF)to treat gastric cancer through network pharmacology and molecular docking methods.Methods LK-ZJF′s active ingredients were collected through TCMSP database and disease gene targets were searched in TTD,DrugBank,Pharmgkb,and so on.The network diagram of the relationship of LK-ZJF′s active ingredients and intersection targets of gastric cancer was constructed using Cytoscape software.The String database was used to build the target protein interaction network(PPI)and select the core targets with Cytoscape software.At the same time,gene ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)enrichment were used to analyze core targets from a macro perspective,and molecular docking possibilities were verified by Autodock software.Results We determined that the main drug active components were quercetin andβ-sitosterol;the core targets were AKT1,TNF,IL6,TP53,and IL1B.KEGG enrichment analysis indicated that PI3K-Akt signaling pathway,inflammation-related signaling pathway may be important pathways.GO analysis suggests that the biological process involved include response to hormone,cellular response to nitrogen compound,cellular response to lipid,etc.And the molecular functions mainly involved include transcription factor binding,protein homodimerization activity,protein domain specific binding,etc.The cellular components involved are transcription regulator complex,membrane raft,plasma membrane protein complex,etc.Molecular docking results showed that the main activity has good binding activity with the core target.Conclusion Studies show that LK-ZJF may act on targets such as AKT1,TNF,IL6,TP53 and IL1B,and play multi-target and multi-pathway effects in treating gastric cancer by regulating PI3K-Akt pathway and inflammation-related pathways.
作者
陈丹媛
罗敏
高卓维
郝民琦
黄景彬
黄玉筠
朱亚莉
聂涛
陈锡传
龙德
林丽珠
CHEN Dan-yuan;LUO Min;GAO Zhuo-wei;HAO Min-qi;HUANG Jing-bin;HUANG Yu-yun;ZHU Ya-li;NIE Tao;CHEN Xi-chuan;LONG De;LIN Li-zhu(Shunde Hospital of Guangzhou University of Traditional Chinese Medicine(Shunde District Cancer Diagnosis and Treatment Center),Foshan,Guangdong 528300;Southern Medical University Southern Hospital Guangzhou 510000,Guangdong;Southern Medical University Integrated Traditional Chinese and Western Medicine Hospital,Guangzhou,Guangdong 510315;Longde of Provincial Famous Traditional Chinese Medicine Inheritance Studio,Foshan,Guangdong 528300;First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405,Guangdong)
出处
《现代消化及介入诊疗》
2023年第9期1117-1124,共8页
Modern Interventional Diagnosis and Treatment in Gastroenterology
基金
广东省自然科学基金区域联合基金项目(2019A1515110416)
广东省中医药局广东省中医师承“薪火工程”(2021[5]号)
龙德省名中医传承工作室项目
林丽珠省名中医传承工作室项目。
关键词
网络药理学
分子对接
龙葵
肿节风
PI3K-AKT信号通路
药对
Gastric cancer
Network Pharmacology
Molecular Docking
Solanum nigrum
Herba Sarcandrae
PI3K-Akt signaling pathway
Couplet medicines
