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. 枸杞子治疗视网膜色素变性分子机制的网络药理学研究[J]. Digital Chinese Medicine, 2019, 2(3): 136-146. DOI: 10.1016/j.dcmed.2019.12.002
引用本文: 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. 枸杞子治疗视网膜色素变性分子机制的网络药理学研究[J]. Digital Chinese Medicine, 2019, 2(3): 136-146. DOI: 10.1016/j.dcmed.2019.12.002
SONG Hou-Pan, ZENG Mei-Yan, CHEN Xiao-Juan, CHEN Xin-Yi, YANG Yi-Jing, ZHOU Ya-Sha, TIAN Ye, LIU Xiao-Qing, CAI Xiong, PENG Qing-Hua, PENG Jun. A Network Pharmacology Approach to Uncover the Molecular Targets and Associated Potential Pathways of Lycii Fructus for the Treatment of Retinitis Pigmentosa[J]. Digital Chinese Medicine, 2019, 2(3): 136-146. DOI: 10.1016/j.dcmed.2019.12.002
Citation: SONG Hou-Pan, ZENG Mei-Yan, CHEN Xiao-Juan, CHEN Xin-Yi, YANG Yi-Jing, ZHOU Ya-Sha, TIAN Ye, LIU Xiao-Qing, CAI Xiong, PENG Qing-Hua, PENG Jun. A Network Pharmacology Approach to Uncover the Molecular Targets and Associated Potential Pathways of Lycii Fructus for the Treatment of Retinitis Pigmentosa[J]. Digital Chinese Medicine, 2019, 2(3): 136-146. DOI: 10.1016/j.dcmed.2019.12.002

枸杞子治疗视网膜色素变性分子机制的网络药理学研究

A Network Pharmacology Approach to Uncover the Molecular Targets and Associated Potential Pathways of Lycii Fructus for the Treatment of Retinitis Pigmentosa

  • 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cytoHubba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。

     

    Abstract:
    ObjectiveTo explore the molecular targets and associated potential pathways of Lycii Fructus (LF, Gou Qi Zi, 枸杞子) in the treatment of retinitis pigmentosa (RP) by the approaches of network pharmacology and bioinformatics.
    MethodsThe potential blood-entry active ingredients and targets of LF were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). RP-related gene targets were retrieved through disease comprehensive databases. Protein-protein interaction (PPI) network of LF component-targets and RP disease-targets was constructed by STRING, and the intersection of the 2 networks was extracted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of theintersection network were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID). CytoHubba was used to screen the key targets.
    ResultsA total of 188 chemical constituents related to LF was retrieved from TCMSP database. 45 active ingredients were screened according to pharmacokinetic parameters oral bioavailability (OB) and drug similarity (DL). 36 active ingredients were further screened and 201 targets related to these constituents were obtained. 206 target genes directly related to RP were obtained from the disease comprehensive databases, and 89 genes were obtained from the intersection of component-target and disease-target PPI network. These genes were mainly involved in intracellular signal transduction, GTPase activity regulation, cell morphology regulation, and other biological processes. Molecular functions were mainly related to Rho guanine nucleotide exchange factor activity, GTPase activator activity, receptor signal protein serine/threonine kinase activity and so on. They were enriched in the cytoplasm, cell membrane, Golgi apparatus, and other regions. The mechanism was related to cell cycle pathways, neurotrophin signaling pathways, Ras signaling pathways, and so on. 10 key gene targets of LF in the treatment of RP were screened.
    ConclusionsThe material basis for LF to exert its pharmacodynamic effect is 36 active ingredients such as cycloartenol, mandenol, and so on. The key targets of LF in the treatment of RP include 10 genes, such as Rho, PAK, and so on. The main mechanism is related to the regulation of the Ras signaling pathway, neurotrophin signaling pathway, cell cycle related pathway, and other signaling networks.

     

/

返回文章
返回