枸杞子治疗视网膜色素变性分子机制的网络药理学研究（英文）

论文摘要

目的采用网络药理学和生物信息学方法探究枸杞子治疗视网膜色素变性（RP）的分子网络调控机制。方法通过中药系统药理学数据库和分析平台（TCMSP）检索枸杞子可能的入血活性成分和作用靶点;通过疾病综合数据库检索与RP相关的基因靶点;采用STRING构建枸杞子成分靶点和RP疾病靶点的蛋白质-蛋白质交互作用（PPI）网络,并提取这两个网络的交集;运用DAVID对交集网络进行基因本体和KEGG通路分析;采用cyto Hubba分析筛选关键靶点。结果在TCMSP数据库共检索出与枸杞子相关的化学成分188个,根据药代动力学参数OB和DL筛得活性成分45个,进一步筛选获得36个入血活性成分,这些成分可能作用于201个基因靶点;从疾病综合数据库获得与RP直接相关的靶基因206个;将成分靶点PPI网络和疾病靶点PPI网络提取交集,得到89个枸杞子治疗RP可能作用的候选基因;这些基因主要涉及细胞内信号转导、GTP酶细胞活性调控、细胞形态调控等生物学过程,分子功能主要涉及Rho鸟嘌呤核苷酸交换因子活性、GTP酶激活剂活性、受体信号蛋白丝氨酸/苏氨酸激酶活性等,富集于细胞质、细胞膜、高尔基体等区域,主要与细胞周期相关通路、神经营养素信号通路、Ras信号通路有关;进一步分析筛选得到枸杞子治疗RP的10个关键性基因靶点。结论枸杞子发挥药效作用的物质基础为环阿屯醇、十八碳-6,9-二烯酸乙酯等36个入血活性成分,其治疗RP的关键靶点包括RHO、PAK等10个基因,主要作用机制与调控Ras信号通路、神经营养素信号通路、细胞周期相关通路等信号网络有关。

论文目录

• 1 Introduction
• 2 Materials and Methods
•   2.1 Databases
•   2.2 Screening of active components from LF and the prediction of their targets
•   2.3 Retrieval of known genes specifically associated with RP
•   2.4 Gene target analysis of LF in the treatment of RP
•   2.5 Gene ontology and pathway enrichment analysis of LF in the treatment of RP
•   2.6 Screening of key targets for LF in the treatment of RP
• 3 Results
•   3.1 Screening of bioactive components from LF and the analysis of pharmacokinetic parameters
•   3.2 Prediction of action targets of LF and visual analysis of bioactive component-target network
•   3.3 Targets retrieval results related to RP occurrence and development
•   3.4 Construction of PPI network and screening of target genes for LF in the treatment of RP
•   3.5 Analysis of GO function enrichment of LF in the treatment of RP
•   3.6 Analysis of KEGG pathway enrichment of LF in the treatment of RP
•   3.7 Screening of key targets for LF in the treatment of RP
• 4 Discussion

文章来源

类型: 期刊论文

作者: 宋厚盼,曾梅艳,陈小娟,陈新怡,杨毅敬,周亚莎,田野,刘晓清,蔡雄,彭清华,彭俊

关键词: 枸杞子,网络药理学,视网膜色素变性,分子机制,靶点,信号通路

来源: Digital Chinese Medicine 2019年03期

年度: 2019

分类: 医药卫生科技

专业: 中药学

单位: 湖南中医药大学中医诊断研究所,湖南中医药大学中医学院,中医药防治眼耳鼻咽喉疾病湖南省重点实验室,湖南中医药大学第一附属医院眼科

基金: funding support from the National Natural Science Foundation of China (No. 81804150 and No. 81703920),Project funded by China Postdoctoral Science Foundation (No. 2019M662790),Natural Science Foundation of Hunan Province,China (No. 2019JJ50442 and No. 2019JJ40226),Research-based Learning and Innovative Experiment Program Project for Hunan University Students (No. 2017280),Scientific Research Project of Hunan Traditional Chinese Medicine Administration (No. 201780),Open Fund Project of Hunan Provincial Key Laboratory for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine (No. 2018YZD05),Open Fund of the Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine (No. 2018ZYX20 and No. 2018ZYX26)

分类号: R285

页码: 136-146

总页数: 11

文件大小: 1051K

下载量: 107