金钱草治疗胆囊相关疾病作用机制的网络药理学研究

Study on Network Pharmacology of the Mechanism of Lysimachia christinae in the Treatment of Cholecyst Related Disease

目的:采用网络药理学方法探究金钱草治疗胆囊相关疾病的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP),以"类药五原则"和"口服吸收利用度(OB)>30%"为标准筛选金钱草活性成分,预测相关靶点,并利用Cytoscape 3.2.1软件构建活性成分-靶点网络;在数据库TTD、OMIM、PharmGKB、DrugBank和GAD中,以"胆石症""胆结石""胆囊炎"和"胆管炎"为关键词预测相关靶点,构建疾病-靶点网络,并与活性成分作用靶点融合,获得治疗靶点,使用数据库DAVID对靶点进行通路富集分析,以靶点与活性成分进行分子对接,以此筛选出金钱草发挥治疗作用的主要成分。结果:筛选获得金钱草中具有类药性、口服吸收较好的27种成分;通过网络构建、融合得到金钱草作用靶点33个,通路富集分析得到相关通路7条,主要涉及癌症通路、ABC转运体通路等;金钱草活性成分中对接得分排序前4位的分别是山柰酚、金合欢素、橙皮素和异鼠李素,主要作用于ABCC3、ABCB1、ABCC2、ABCB4靶点。结论:金钱草主要通过ABC转运体通路发挥治疗胆囊相关疾病的作用。

OBJECTIVE:To explore the mechanism of Lysimachia christinae in the treatment of cholecyst related diseases by network pharmacology. METHODS:The active ingredients of L. christinae were screened through TCMSP database with“Lipinski rule”and“Oral bioavailability >30%”rules,and their related targets were predicated correspondingly,then compound-target network were constructed by Cytoscape 3.2.1 software. Disease related targets were predicted by searching TTD database,OMIM database,PharmGKB database,DrugBank database and GAD database with“cholelithiasis”“gallstones”“cholecystitis”and “cholangitis”as keywords. Then,the network of disease-target was constructed and merged with active ingredient target to obtain therapeutic target. After pathway enrichment analysis of therapeutic target were performed by utilizing the DAVID database, molecular docking between target and active ingredient was also conducted in order to screen the main active ingredients of L. christinae. RESULTS:Twenty-seven active ingredients with good oral absorption and drug-like properties were screened from L. christinae. Thirty-three targets were attained after constructing and merging the network. Seven pathways,mainly related to cancer pathway and ABC transporter pathway were achieved. Top 4 active ingredients of L. christinae in the list of docking score were kaempferin,acacia,hesperetin and isorhamnetin,which acted on ABCC3,ABCB1,ABCC2,ABCB4 target. CONCLUSIONS:L. christinae treat cholecyst related diseases through ABC transporter pathway.