Study on Mechanism of Nephrotoxicity of Tripterygii Radix et Rhizoma Based on Network Pharmacology

Jun-xia HAO; Zi-sen GAO; Hao GAO; Kai-shun BI; Jian WANG; Zuo-jing LI

doi:10.13422/j.cnki.syfjx.20191638

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Study on Mechanism of Nephrotoxicity of Tripterygii Radix et Rhizoma Based on Network Pharmacology

Data Mining | 更新时间：2021-02-09

- Study on Mechanism of Nephrotoxicity of Tripterygii Radix et Rhizoma Based on Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 16, Pages: 142-151(2019)
- 作者机构：
  
  沈阳药科大学　药学院，制药工程学院，医疗器械学院，沈阳　 110016
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191638
  CLC： R2-0; R285.5
- Received：23 March 2019，
  
  Published Online：08 May 2019，
  
  Published：20 August 2019
- 稿件说明：
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Jun-xia HAO, Zi-sen GAO, Hao GAO, et al. Study on Mechanism of Nephrotoxicity of Tripterygii Radix et Rhizoma Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 142-151.
DOI：

Jun-xia HAO, Zi-sen GAO, Hao GAO, et al. Study on Mechanism of Nephrotoxicity of Tripterygii Radix et Rhizoma Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(16): 142-151. DOI： 10.13422/j.cnki.syfjx.20191638.

摘要

目的：

通过建立雷公藤活性成分-作用靶点、蛋白相互作用、靶点相应的生物功能和通路网络，以及利用分子对接技术探讨雷公藤肾毒性的作用机制。

方法：

通过中药系统药理学数据库与分析平台(TCMSP)和毒性与基因比较数据库(CTD)筛选出雷公藤有毒候选化合物。用有机小分子生物活性数据PubChem数据库，将所有的候选化合物都转化为标准的Canonical SMILES格式，将SMILES格式文件导入SwissTargetPrediction平台，进行靶点预测，将TCMSP中相应化合物的靶点作为补充，用uniprot将蛋白转换为对应的基因名称，与从人类基因组注释数据库(GeneCards)中寻找到的肾脏相关基因蛋白进行比对，筛选出重合的蛋白作为雷公藤潜在的肾脏毒性靶点。采用Cytoscape软件构建雷公藤毒性候选成分-作用靶点网络。通过String数据库结合Cytoscape软件绘制蛋白相互作用网络，用DAVID生物信息资源对靶点生物功能及涉及的通路进行分析，最后用Glide软件对关键蛋白与雷公藤毒性候选成分的结合进行验证。

结果：

雷公藤中筛选得到30种有毒候选成分，涉及209个肾脏毒性作用靶点，网络分析结果表明雷公藤可通过氨基酸代谢、磷脂代谢、儿茶酚胺类物质代谢，抑制肾脏有机阴离子转运体Oatl，Oat2，Oat3的功能，以及诱导凋亡，并参与丝裂原活化蛋白激酶(MAPK)信号通路，JAK/STAT信号通路，血管内皮生长因子(VEGF)信号通路，Toll样受体信号通路，ERBB信号通路，Fc

RI信号通路，过氧化物酶体增殖剂激活受体(PPAR)信号通路等对肾脏产生毒性。

结论：

利用中药多成分-多靶点-多通路的特点，探究了雷公藤肾脏毒性作用机制，为进一步开展雷公藤肾脏毒性作用机制研究提供了新思路和新方法。

Abstract

Objective:

To explore the mechanism of renal toxicity of Tripterygii Radix et Rhizoma by establishing the active component-target

protein interaction

biological function and pathway network corresponding to the target

and using molecular docking technology.

Method:

The traditional Chinese medicine(TCM) systems pharmacology database(TCMSP) and the comparative toxicogenomics database (CTD) were used to screen The toxic candidate compounds.In PubChem database

convert all candidate compounds into standard Canonical SMILES format

SMILES format file import SwissTargetPrediction platform

target prediction

will be the target of the corresponding compounds in TCMSP supplement with uniprot converts protein antipodal gene name

and from the human genome database (GeneCards) seek to compare the renal related gene protein

overlapping proteins were screened as potential renal toxicity targets of Tripterygii Radix et Rhizoma.Cytoscape software was used to construct the candidate components-target network of Tripterygii Radix et Rhizoma.Cytoscape software was combined with String database to draw the protein interaction network

DAVID platform was used to analyze the biological function of the target and the pathways involved

and Glide software was used to verify the combination of the key protein and the candidate components of tripterygiumwildiitoxicity.

Result:

The screening of 30 kinds of candidates for toxic ingredients of Tripterygii Radix et Rhizoma

involving 209 renal toxicity targets

network analysis results showed that Tripterygii Radix et Rhizoma by amino acid metabolism

phospholipid metabolism

catecholamine metabolism

inhibiting renal organic anion transporter Oatl

Oat2

Oat3 function

and inducing apoptosis

and participate in the mitogen-activated protein kinase(MAPK) signaling pathways

JAK-STAT signaling pathway

vascular endothelial growth factor(VEGF)signaling pathways

Toll-like receptor signaling pathway

ERBB signaling pathway

RI signaling pathway

peroxisome proliferators-activated receptors(PPAR) signaling pathway such as toxic to the kidneys.

Conclusion:

The mechanism of kidney toxicity of Tripterygii Radix et Rhizoma was explored by using the characteristics of multi-component

multi-target and multi-pathway of TCM

which provided new ideas and methods for further research on the mechanism of kidney toxicity of Tripterygii Radix et Rhizoma.

关键词

Keywords

references

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