基于网络药理学方法探究中药肉桂治疗糖尿病的作用机制

doi:10.3976/j.issn.1002-4026.2020.06.007

摘要/Abstract

摘要： 运用网络药理学方法和生物信息学技术，预测中药肉桂治疗糖尿病的药效成分及关键靶点，分析其作用机制。通过中药系统药理学数据库与分析平台（Traditional Chinese Medicine System Pharmacology Database and Analysis Platform，TCMSP）以及文献检索，确定肉桂的有效成分并筛选出肉桂对应靶点蛋白；利用GeneCards数据库筛选糖尿病相关基因，构建中药肉桂的成分-靶点网络和蛋白质-蛋白质相互作用（protein-protein interaction,PPI）网络；利用DAVID(Database for Annotation, Visualization and Integrated Discovery)和STRING数据库进行基因本体（gene ontology，GO）功能富集分析和京都基因和基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析；最后，将部分药效成分与关键靶点进行分子对接验证。通过筛选，得到32个有效成分作用于131个相关靶点，核心基因有INS、AKT1、IL6、TNF、VEGFA等20个，GO和KEGG分析肉桂主要参与RNA聚合酶II启动子对转录的正调控等生物过程及糖尿病并发症中的AGE-RAGE信号通路、IL-17信号通路等发挥治疗作用。对10个关键成分进行分子对接得出，肉桂中的原花青素B1和槲皮素与INS、IL6、VEGFA、TNF有较好的亲和力。本研究初步阐释了肉桂治疗糖尿病的作用机制，有利于指导临床用药。

关键词: 肉桂, 糖尿病, 网络药理学, 分子对接技术

Abstract: To predict the active components and key targets of Cinnamomi Cortex in the treatment of diabetes and analyze its mechanisms using bioinformatics technology and network pharmacology. The effective compounds and the corresponding target proteins of Cinnamomi Cortex were determined and screened using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP) database and a literature search. Diabetes-related genes were obtained from the GeneCards Database, and the compound-target network and the protein-protein interaction (PPI) network were constructed. Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were conducted using the Database for Annotation, Visualization and Integrated Discovery(DAVID) and STRING databases. Molecular docking was performed between active components and key targets. Overall, 32 active components were found to act on 131 related targets and 20 core genes such as INS, AKT1, IL6, TNF, and VEGFA. GO and KEGG analysis showed that Cinnamomi Cortex was mainly involved in biological processes such as positive regulation of transcription by RNA polymerase II promoter, as well as pathways covering the AGE/RAGE signaling pathway in diabetic complications and IL-17 signaling pathway. The results of molecular docking of 10 key components showed that quercetin and procyanidin B1 in Cinnamomi Cortex had better affinity with INS, IL6, VEGFA, and TNF. This study preliminarily explained the mechanism of Cinnamomi Cortex in in treatment of diabetes, which will be helpful to guide the clinical use of drugs.

Key words: Cinnamomi Cortex, diabetes, network pharmacology, molecular docking

中图分类号:

R285.5

王珺, 苏本正, 蒋海强, 孙雨, 杨钰涵, 崔宁, 于宗渊. 基于网络药理学方法探究中药肉桂治疗糖尿病的作用机制[J]. 山东科学, 2020, 33(6): 44-54.

WANG Jun, SU Ben-zheng, JIANG Hai-qiang, SUN Yu, YANG Yu-han, CUI Ning, YU Zong-yuan. Exploration of the mechanisms of Cinnamomi Cortex in the treatment of diabetes based on network pharmacology[J]. Shandong Science, 2020, 33(6): 44-54.

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