Molecular Mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma in Treatment of Retinitis Pigmentosa

Hou-pan SONG; Mei-yan ZENG; Jun PENG; Xiao-juan CHEN; Xin-yi CHEN; Wei-bo HE; Yi-jing YANG; Xiong CAI; Qing-hua PENG

doi:10.13422/j.cnki.syfjx.20191205

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Molecular Mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma in Treatment of Retinitis Pigmentosa

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- Molecular Mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma in Treatment of Retinitis Pigmentosa
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 14, Pages: 199-206(2019)
- 作者机构：
  
  1.湖南中医药大学　中医诊断研究所，长沙　 410208；
  2.湖南中医药大学　中医学院，长沙　 410208；
  3.湖南中医药大学　中医药防治眼耳鼻咽喉疾病湖南省重点实验室，长沙　 410208；
  4.湖南中医药大学　第一附属医院，长沙　 410007
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191205
  CLC： R2-0; R22; R285.5
- Published：20 July 2019，
  
  Published Online：01 March 2019，
  
  Received：05 December 2018，
- 稿件说明：
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Hou-pan SONG, Mei-yan ZENG, Jun PENG, et al. Molecular Mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma in Treatment of Retinitis Pigmentosa. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(14):199-206(2019)
DOI：

Hou-pan SONG, Mei-yan ZENG, Jun PENG, et al. Molecular Mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma in Treatment of Retinitis Pigmentosa. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(14):199-206(2019) DOI： 10.13422/j.cnki.syfjx.20191205.

摘要

目的：

基于网络药理学和生物信息学方法探讨枸杞子-丹参(LFSMR)药对治疗视网膜色素变性(RP)的分子机制。

方法：

通过中药系统药理学数据库和分析平台(TCMSP)筛选和预测LFSMR药对可能的入血活性成分和作用靶点；通过疾病基因数据库挖掘视网膜色素变性相关的基因靶点；采用功能蛋白联合网络数据库(STRING)绘制成分-靶点和疾病-靶点的蛋白质-蛋白质交互作用(PPI)网络，并取这两个网络的交集；运用注释、可视化和整合发现数据库(DAVID)对交集网络进行基因本体和京都基因与基因组百科全书(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LFSMR相关的活性成分390个，根据药代动力学参数筛得活性成分110个，进一步筛选获得19个入血活性成分，并检索出与这些成分相关的靶点208个；从疾病基因数据库获得与RP直接相关的基因206个；成分靶点和疾病靶点PPI网络取交集后得到79个基因；这些基因主要涉及蛋白自体磷酸化、转录调节、细胞增殖等生物学过程，分子功能主要涉及三磷酸腺苷结合、转录因子活性、核心启动子结合等，富集于核质、转录因子复合物、细胞核、细胞质等区域，主要与神经营养素信号通路，细胞周期相关通路，Wnt信号通路有关；进一步分析筛选得到LFSMR治疗RP的8个关键性基因靶点。

结论：

LFSMR药效作用的物质基础为多孔甾醇、丹参酮Ⅱ

等19个入血活性成分，其治疗RP的关键靶点包括E2F转录因子1(E2F1)，视网膜母细胞瘤基因1(RB1)等8个基因，主要作用机制与调控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

Objective:

To explore the molecular mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma (FLRSM) in the treatment of retinitis pigmentosa (RP) based on network pharmacology and bioinformatics.

Method:

Possible intake active components and targets of FLRSM were screened out and predicted by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP). Gene targets related to RP were mined through disease gene databases. Protein-protein interaction (PPI) network of component-targets and disease-targets were mapped by functional protein association networks (STRING)

and the intersection of the two networks was obtained. The gene ontology and kyoto encyclopedia of genes and genomes(KEGG) pathway of the intersection network were analyzed by the database for annotation

visualization and integrated discovery(DAVID). CytoHubba analysis was used to screen out the key targets.

Result:

A total of 390 active ingredients related to FLRSM were retrieved from TCMSP. According to pharmacokinetic parameters

110 active ingredients were screened out

19 active ingredients were further screened out

and 208 targets related to these constituents were retrieved. Totally 206 genes directly related to RP were obtained from the disease gene databases. And 79 genes were obtained from the intersection of PPI networks of component targets and disease targets. These genes mainly involved in biological processes

such as protein autophosphorylation

transcriptional regulation and cell proliferation

and the molecular functions mainly involved adenosine triphosphate binding

transcription factor activity

core promoter binding

and were enriched in nuclear

transcription factor complex

nucleus

cytoplasm and other regions. It was mainly related to neurotrophin signaling pathway

cell cycle related pathway and Wnt signaling pathway. And 8 key gene targets for FLRSM treatment of RP were identified by further screening.

Conclusion:

The material basis of pharmacodynamic action of FLRSM involves 19 active ingredients

such as porous sterol and tanshinone Ⅱ

. The key targets of FLRSM in the treatment of RP include 8 genes

such as E2F transcription factor 1(E2F1) and retinoblastoma gene1(RB1). The main mechanism is related to the regulation of neurotrophin signaling pathways

cell cycle related pathways and other signaling networks.

关键词

视网膜色素变性枸杞子丹参网络药理学生物信息学分子机制

Keywords

retinal pigmentationLycii FructusSalviae Miltiorrhizae Radix et Rhizomanetwork pharmacologybioinformaticsmolecular mechanism

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