基于网络药理学和分子对接技术探讨败酱草-赤芍药对治疗结肠直肠癌的作用机制  

Mechanism of Herba Patriniae-Paeoniae Radix Rubra herb pair in the treatment of colorectal cancer based on network pharmacology and molecular docking

作　　者：邢亚东 武敏 罗凯文 孙大伟 常伟 XING Yadong;WU Min;LUO Kaiwen;SUN Dawei;CHANG Wei(College of Pharmacy,Bengbu Medical University,Bengbu,AnHui,233030,China;Internal Medicine Department,Suzhou First People's Hospital,Suzhou,Anhui,234000,China;Quality Control Laboratory,Anhui Golden Sun Biochemical Pharmaceutical Co.,LTD,Yingshang,Anhui,236000,China;Graduate School,Anhui Medical University,Hefei,AnHui,230032,China)

机构地区：[1]蚌埠医科大学药学院,安徽蚌埠233030 [2]宿州市第一人民医院内科,安徽宿州234000 [3]安徽金太阳生化药业有限公司检验室,安徽颖上2236000 [4]安徽医科大学研究生院,安徽合肥230032

出　　处：《甘肃中医药大学学报》2024年第5期54-64,共11页Journal of Gansu University of Chinese Medicine

基　　金：安徽省重点研究与开发计划(长三角科技创新联合攻关专项)项目(202104g01020017);2021年省级大学生创新创业训练计划项目(S202110367085);蚌埠医学院自然科学重点项目(2021byzd034)。

摘　　要：目的基于网络药理学和分子对接技术探讨败酱草-赤芍药对治疗结肠直肠癌(CRC)的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)检索并筛选败酱草、赤芍的有效成分及靶点,在GeenCards、DrugBank、BharmGKB数据库中查找CRC相关靶点;使用Cytoscape 3.8.0软件绘制有效成分-疾病-靶点可视化网络图,通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,得核心基因;利用R软件及相关软件包对结果进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,对得到的核心成分和核心靶点借助AutoDock Vina软件进行分子对接。结果从败酱草-赤芍药对中挖掘出有效成分42种,潜在靶点1486个,CRC相关靶点2976个,最终得到药物和疾病共有靶点143个;治疗疾病的重要靶点有骨髓瘤细胞癌基因(MYC)、丝裂原活化蛋白激酶(MAPK)14、原癌基因蛋白(FOS)、缺氧诱导因子1α(HIF1A)、MAPK1,主要作用于p53、磷脂酰肌醇-3-激酶(PI3K-Akt)、白细胞介素-17(IL-17)、肿瘤坏死因子(TNF)等信号通路;分子对接结果显示,败酱草-赤芍药对的主要化合物和核心靶点之间结合能均小于-7 kcal/mol,结合良好。结论败酱草-赤芍可能通过调节MYC、MAPK14、FOS、HIF1A、MAPK1等靶点发挥抗肿瘤、抗炎、抗病毒、抗氧化等功效,从而发挥治疗CRC的作用。Objective To investigate the mechanism of Herba Patriniae-Paeoniae Radix Rubra herb pair in the treatment of colorectal cancer(CRC)using network pharmacology and molecular docking techniques.Methods The active components and targets of Herba Patriniae-Paeoniae Radix Rubra were identified through TCMSP,while CRC-related targets were obtained from GeenCards,DrugBank,and BharmGKB databases.Cytoscape 3.8.0 software was utilized to visualize the active ingredient-target network,and the protein-protein interaction(PPI)network was constructed using STRING database to identify core genes.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed using R software,followed by molecular docking using AutoDock Vina software.Results A total of 42 active ingredients,1486 potential targets,and 2976 CRC-related targets were identified for the Herba Patriniae-Paeoniae Radix Rubra herb pair.Ultimately,143 drug-disease targets were obtained.Key targets for treating CRC included myeloma cell oncogene(MYC),mitogen-activated protein kinase(MAPK)14,proto-oncogene protein(FOS),hypoxia-inducing factor 1α(HIF1A),MAPK1,as well as their involvement in signaling pathways such as p53,phosphatidylinositol-3-kinase(PI3K-Akt),interleukin-17(IL-17),tumor necrosis factor(TNF).Molecular docking results indicated favorable binding between the main compounds and core targets with a free binding energy less than-7 kcal/mol.Conclusion It is suggested that Herba Patriniae-Paeoniae Radix Rubra herb pair may exert anti-tumor,anti-inflammatory,antiviral,and antioxidant effects by regulating MYC,MAPK14,FOS,HIF1A,and MAPK1 among other key targets in order to effectively treat CRC.

关 键 词：结肠直肠癌 败酱草 赤芍 网络药理学 分子对接 作用机制 

分 类 号：R285.6[医药卫生—中药学] R273.535[医药卫生—中医学]