丹参饮治疗糖尿病心肌病的网络药理学研究

目的通过整合网络药理学和生物信息学方法,构建活性成分-作用靶点、蛋白-蛋白相互作用(PPI)、关键靶点相应的生物功能和通路网络,预测丹参饮治疗糖尿病心肌病的分子作用机制。方法采用中药系统药理学数据库和分析平台(TCMSP)数据库筛选及预测丹参饮的生物活性成分及其潜在作用靶点,同时检索PharmGKB等4个数据库挖掘糖尿病心肌病的相关靶点,对2种靶点进行PPI网络构建,交互处理得到丹参饮治疗糖尿病心肌病的关键靶点,并利用SystemsDock WebSite对其进行分子对接验证;运用DAVID(Version 6.8)平台对关键靶点进行Pathway分析,结合Omicshare数据库筛选核心通路并利用Reactome数据库进行注释。结果以口服生物利用度(OB)和类药性(DL)数值作为筛选标准,从丹参饮中共获得78个活性成分,涉及到506个丹参饮治疗糖尿病心肌病的可能靶点,这些靶点主要富集在磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)等多条信号通路上。结论本研究揭示了丹参饮治疗糖尿病心肌病可能的作用机制,体现了中药复方多成分、多靶点、多途径治疗疾病的特点,为进一步深入研究其作用机制提供了新思路。

Network pharmacology study on Danshen Decoction in treatment of diabetic cardiomyopathy

Objective Based on the network pharmacology and bioinformatics methods, the networks of active components-targets, protein-protein interactions, and the corresponding biological functions and pathways of key targets were established to predict the molecular mechanism of Danshen Decoction in the treatment of diabetic cardiomyopathy. Methods TCMSP database was used to screen and predict the bioactive components of Danshen Decoction and potential targets. Four databases including PharmGKB were searched for related targets of diabetic cardiomyopathy. The PPI network was constructed for the two types of targets. The key targets were obtained by interactive processing and verified by molecular docking by SystemsDock Web Site. Pathway analysis was performed on the key targets using the DAVID platform (Version 6.8), and the core pathway was screened by Omicshare database and annotated by using Reactome database. Results Taking oral bioavailability (OB) and drug-like (DL) as screening criteria, 78 active ingredients were screened from Danshen Decoction, involving 506 potential targets for treating of diabetic cardiomyopathy. These targets were mainly rich in PI3K-Akt, MAPK and other signaling pathways. Conclusion This study reveals the possible mechanism of Danshen Decoction in the treatment of diabetic cardiomyopathy, embodying the characteristics of multi-component, multi-target and multi-channel of Traditional Chinese Medicine compound, which provides a new idea for further research on its mechanism of action.