双黄连抗结肠癌活性组分中药的发现和验证  

Discovery and Verification of Multi-component Chinese Medicine with Anti-tumor Activity from Shuanghuanglian

作　　者：魏佩煌 张玮[1] 李城 陶仕英[1] 蔡程科[1] 李强[1] 李健[1] WEI Pei-huang;ZHANG Wei;LI Cheng;TAO Shi-ying;CAI Cheng-ke;LI Qiang;LI Jian(Bejing University of Chinese Medicine,Beiing 100029,China)

机构地区：[1]北京中医药大学,北京100029

出　　处：《中国实验方剂学杂志》2020年第15期69-74,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家“重大新药创制”科技重大专项(2011ZX09201-201-15);北京中医药大学在读研究生科研项目(2019-JYB-XS-0181)。

摘　　要：目的:应用网络药理学方法,从双黄连方剂中预测具有抗肿瘤活性的组分中药,并通过离体细胞实验与动物实验对其抗CT26结肠癌活性进行初步验证。方法:基于中药系统药理学数据库(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP),《中药活性成分分析手册》,药品生物信息学和化学信息学数据库(DrugBank),信号通路数据库(Reactome)及人类蛋白质参考数据库(Human protein reference database,HPRD),构建蛋白-蛋白相互作用网络(proteinprotein interactions network,PPI)和化合物靶标网络,挖掘化合物的药理作用,发现与PPI网络节点距离较短的化合物,确定组成中药的配伍。以CT26结肠癌细胞为实验材料,结合离体和在体实验初步验证组分中药的抗肿瘤作用。结果:从双黄连组分中预测并发现"黄芩苷、连翘酯苷A和绿原酸"3个化合物配伍具有潜在抗肿瘤活性。验证结果表明,细胞实验中,与空白组比较,双黄连组分中药能显著抑制CT26细胞的增殖和迁移(P<0.01);动物实验中,与荷瘤模型组比较,双黄连组分中药治疗组小鼠皮下肿瘤体积增长缓慢、肿瘤重量显著降低(P<0.01)。结论:结合数据库挖掘和化合物靶点网络构建、分析等方法从双黄连方剂中发现具有抗肿瘤活性的组分中药"黄芩苷、连翘酯苷A和绿原酸"。经验证,该组分中药具有较好的抗CT26结肠癌活性。Objective:The methods of network pharmacology were adopted to predict Multi-component Chinese Medicine(MCCM)with anti-tumor activity from Shuanghuanglian(SHL).Furthermore,the pharmaceutical activity of CT26 colon cancer was verified in vitro and in vivo.Method:Based on the Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),the Handbook of Active Components Analysis of Traditional Chinese Medicine,the Drugbank database,the Reactome database,and the Human protein reference database(HPRD),the protein-protein interactions network(PPI)and the drug target network were built and resolved.The data was mined to discover the pharmacological effect.The anti-tumor activity of components from SHL was determined based on the nearest distance rule between the compounds and the nodes of network.And then,the anti-tumor effect of the MCCM was verified in vitro and in vivo.Result:The 3 combined compounds,baicalin,forsythoside A and chlorogenic acid with the anti-tumor activity from SHL were predicted and discovered.The verification results showed that the combination of baicalin-forsythoside A-chlorogenic acid could significantly inhibit the cell proliferation and migration compared with the control group in vitro(P<0.01).Among CT26 bearing mice,the tumor volume and weight were significantly decreased after the combined administration of baicalin-forsythoside A-chlorogenic acid compared with the model group in vivo(P<0.01).Conclusion:By the methods of network pharmacology,the anti-tumor activities of component of from SHL were discovered.According to the verification in vitro and in vivo,the combination of baicalin-forsythoside A-chlorogenic acid could play better anti-CT26 tumor activity.

关 键 词：双黄连 组分中药 抗肿瘤 肠癌 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]