Cardiotoxicity of Aconiti Kusnezoffii Radix Based on Network Toxicology

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

doi:10.13422/j.cnki.syfjx.20191425

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Cardiotoxicity of Aconiti Kusnezoffii Radix Based on Network Toxicology

Data Mining | 更新时间：2021-02-09

- Cardiotoxicity of Aconiti Kusnezoffii Radix Based on Network Toxicology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 19, Pages: 161-169(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.20191425
  CLC： R22; R242; R2-031; R285.5;R287
- Received：21 October 2018，
  
  Published Online：04 April 2019，
  
  Published：05 October 2019
- 稿件说明：
移动端阅览
Jun-xia HAO, Zi-sen GAO, Hao GAO, et al. Cardiotoxicity of Aconiti Kusnezoffii Radix Based on Network Toxicology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(19): 161-169.
DOI：

Jun-xia HAO, Zi-sen GAO, Hao GAO, et al. Cardiotoxicity of Aconiti Kusnezoffii Radix Based on Network Toxicology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(19): 161-169. DOI： 10.13422/j.cnki.syfjx.20191425.

摘要

目的：

通过建立草乌活性成分-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草乌心脏毒性的作用机制。

方法：

通过中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology

TCMSP)和毒性与基因比较数据库(Comparative Toxicogenomics Database，CTD)筛选出草乌有毒候选成分。依据反向药效团匹配(PharmMapper)方法预测草乌毒性候选成分的作用靶点，与从人类基因数据库(GeneCards)中寻找到的心脏相关基因蛋白进行比对，筛选出重合的蛋白作为草乌的潜在的心脏毒性靶点。采用Cytoscape软件构建草乌毒性候选成分-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平台对靶点生物功能及涉及的通路进行分析，最后用Discover Studio软件对关键蛋白与草乌毒性候选成分的结合进行验证。

结果：

草乌中筛选得到6种有毒候选成分，涉及27个心脏毒性作用靶点，网络分析结果表明靶点主要是通过参与心脏磷代谢，磷酸化的监管等磷相关的代谢和调节，以及通过FKBP1A，TGFB2，INSR等靶点对心脏的代谢，发育及形态产生重要的影响，进而产生心脏毒性。

结论：

利用中药多成分-多靶点-多通路的特点，探究了草乌心脏毒性作用机制，并预测了其可能存在的毒性，为进一步开展草乌心脏毒性作用机制研究提供了新思路和新方法。

Abstract

Objective:

The mechanism of action of cardiac toxicity of Radix Aconiti Agrestis was explored by establishing the active components-targets network of Radix Aconiti Agrestis

protein interaction network

the biological function and pathway network of targets

and using molecular docking technology.

Methods:

The Traditional Chinese Medicine Systems Pharmacology(TCMSP) database and the Comparative Toxicogenomics Database(CTD) were used to filtrate the toxic candidates of Radix Aconiti Agrestis. Predicting the functional targets of toxic candidates of Radix Aconiti Agrestis by PharmMapper and compared with the cardiac related gene proteins found in the human gene database (GeneCards)

and the overlapping proteins were selected as potential cardiac toxicity targets of Radix Aconiti Agrestis. The Cytoscape software was used to construct the network between toxic candidate components and targets. The protein interaction network was mapped by the String database combined with Cytoscape software. The biological functions of the targets and the involved pathways were analyzed with the DAVID platform.The binding of the key proteins with certain toxic candidate components of Radix Aconiti Agrestis was verified by Discover Studio software finally.

Results:

There were six candidates for toxic ingredients

which involving 27 cardiac toxicity targets. Network analysis results show that the targets were mainly by participating in the heart of phosphorus metabolism

regulation and other related phosphorus metabolism and regulation of phosphorylation and FKBP1A

TGF4-

INSR targets to have an important impact on the metabolism

development and form of the heart

and further to have cardiac toxicity.

Conclusion:

Based on the characteristics of the multi-component

multi-target and multi-pathway of traditional Chinese medicine

the mechanism of cardiac toxicity of Radix Aconiti Agrestis was explored and its possible toxicity was predicted

which provided a new idea and method for further research on the mechanism of cardiac toxicity of Radix Aconiti Agrestis.

关键词

Keywords

references

田玥．草乌的毒性研究现状 [J]．医学信息， 2015 ， 28 ( 1 )： 371 - 371 ．

段斌．草乌中毒患者的急救探讨 [J]．中国医疗前沿， 2009 ， 4 ( 19 )： 31，33 ．

Kim S C , HA Y R , Kim Y S , et al . An outbreak of Caowu-intoxication after drinking home-brewed alcohol [J]. Ko Mcl , 2008 , 19 ( 3 ): 339 - 345 .

XIAO K , YAN G Y , WANG L , et al . Toxicity of Caowu on in vitro cultured rat embryos [J]. J Sichuan Univer: Med Sci Edit , 2008 , 39 ( 3 ): 441 .

CHAN T Y , Tomlinson B , Tse L K , et al . Aconitine poisoning due to Chinese herbal medicines: a review . [J]. Vet Hum Toxicol , 1994 , 36 ( 5 ): 452 - 455 .

范骁辉，赵筱萍，金烨成，等．论建立网络毒理学及中药网络毒理学研究思路 [J]．中国中药杂志， 2011 ， 36 ( 21 )： 2920 - 2922 ．

刘睿，李新宇，李亚卓，等．网络毒理学及其在中药毒性成分预测中的应用研究 [J]．药物评价研究， 2018 ， 41 ( 5 )： 709 - 715 ．

张舒涵，李晋奇．乌头碱心脏毒性作用机制的研究进展 [J]．中西医结合心脑血管病杂志， 2018 ， 16 ( 10 )： 1366 - 1370 ．

师帅，胡元会，吴华芹，等． “丹参-三七”药对作用机制的网络药理学探讨 [J]．中国实验方剂学杂志， 2018 ， 24 ( 18 )： 192 - 197 ．

程菲，姜红堃． TBX1基因可能通过调控TGF-β2基因的表达参与心脏发育及先天性心脏病的发生 [J]．中国中西医结合儿科学， 2018 ， 10 ( 1 )： 36 - 39 ．

豆亚伟．儿童围心脏手术期强化胰岛素治疗的方法及机制研究 [D]．西安：第四军医大学， 2008 ．

付锋．缺血后心肌胰岛素抵抗促发缺血性心力衰竭及其机制 [D]．西安：第四军医大学， 2015 ．

刘鑫馗，吴嘉瑞，张丹，等．基于网络药理学的附子-干姜药对治疗心力衰竭的作用机制分析 [J]．中国实验方剂学杂志， 2017 ， 23 ( 21 )： 212 - 219 ．

吴秀君，郭涛．细胞色素P450 2C8基因多态性及其对药物代谢影响的研究进展 [J]．中国临床药理学杂志， 2013 ， 29 ( 3 )： 234 - 237 ．

杨晓珊． CYP450酶与BCRP、MRP2外排转运蛋白对单酯型及醇胺型乌头生物碱处置的作用和机制 [D]．广州：南方医科大学， 2014 ．

杨欣，李亚辉，钱海兵，等．基于网络药理学及分子对接分析熊果酸抗类风湿性关节炎的分子机制 [J]．中国实验方剂学杂志， 2018 ， 24 ( 18 )： 207 - 214 ．

陆彤，蒋彬．心肌细胞钙离子通道 [J]．中国心脏起搏与心电生理杂志， 2008 ， 22 ( 6 )： 477 - 482 ．

肖凯，王莉，刘玉清，等．草乌的体外胚胎发育毒性研究 [J]．毒理学杂志， 2007 ， 21 ( 4 )： 317 ．

王文文，田杰，郑敏，等． TGF-β2对心肌细胞H9C2转录因子表达的影响及其组蛋白H3乙酰化调控机制 [J]．第三军医大学学报， 2013 ， 35 ( 7 )： 639 - 643 ．

邓建英．圆锥动脉干畸形与视黄酸信号传导通路关系的研究进展 [J]．国际儿科学杂志， 2014 ， 41 ( 1 )： 29 - 32 ．

杨俊平，方五旺．血管紧张素转换酶2与心血管疾病 [J]．安徽医药， 2013 ， 17 ( 5 )： 861 - 863 ．

林琳，李阳，刘云奇，等． CTSB对人脐静脉血管内皮细胞系增殖及凋亡的影响 [J]．现代生物医学进展， 2016 ， 16 ( 4 )： 611 - 615 ．

李建良，梁慧，蔡淑珍，等．基于网络药理学探讨蒙药诃子解草乌心脏毒的机制研究 [J]．药学学报， 2018 ， 53 ( 10 )： 1670 - 1679 ．

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