Screening of Antitumor Active Components and Key Targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma Based on PI3K/Akt Pathway

Xin YANG; Ya-hui LI; Si-jia PAN; Yao-feng LI; Xiang-yun CHEN; Chang-fu YANG

doi:10.13422/j.cnki.syfjx.20191026

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Screening of Antitumor Active Components and Key Targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma Based on PI3K/Akt Pathway

Data Mining | 更新时间：2021-02-09

- Screening of Antitumor Active Components and Key Targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma Based on PI3K/Akt Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 10, Pages: 170-179(2019)
- 作者机构：
  
  贵阳中医学院，贵阳　 550025
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191026
  CLC： R22; R242; R2-031; R285.5
- Received：22 October 2018，
  
  Published Online：12 February 2019，
  
  Published：20 May 2019
- 稿件说明：
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Xin YANG, Ya-hui LI, Si-jia PAN, et al. Screening of Antitumor Active Components and Key Targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma Based on PI3K/Akt Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(10): 170-179.
DOI：

Xin YANG, Ya-hui LI, Si-jia PAN, et al. Screening of Antitumor Active Components and Key Targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma Based on PI3K/Akt Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(10): 170-179. DOI： 10.13422/j.cnki.syfjx.20191026.

摘要

目的：

以附子-半夏化学成分为切入点，基于系统药理学筛选附子-半夏抗肿瘤的活性成分，为开发附子-半夏抗肿瘤的无毒活性成分提供理论依据。

方法：

借助Traditional Chinese Medicine Systems Pharmacology(TCSMP)平台构建附子-半夏小分子配体库；基于分子对接(SYBYL2.1，Tripos)将附子-半夏小分子与磷脂酰肌醇-3-激酶(phosphatidylinositol 3-kinase，PI3K)/蛋白激酶B(protein kinase B，Akt)信号通路中的关键靶标蛋白进行能量匹配；借助Cytoscape 3.5.1构建附子-半夏活性成分-靶标网络模型；基于Ligplot计算小分子与靶标蛋白形成的氢键、疏水作用和结构比对；附子-半夏抗肿瘤活性成分的理化性质基于SwissADME和admetSAR进行预测。

结果：

附子-半夏小分子活性成分25个，通过能量匹配发现半夏抗肿瘤的关键活性成分为11-二十碳烯酸，10，13-二十碳二烯酸，黄芩苷，12，13-环氧-9-羟基十九碳-7，10-二烯酸；附子抗肿瘤关键活性成分为deltoin，谷甾醇，neokadsuranic acid B，11，14-二十碳二烯酸。磷脂酰肌醇三激酶

(PI3K

)，类脂磷酸酶(PTEN)，3-磷酸肌醇依赖性蛋白激酶1(PDK1)为附子-半夏抗肿瘤的关键靶标蛋白。附子-半夏8个关键活性成分具有较低的CYP450抑制性，基本遵循Lipinski规则。

结论：

从分子层面筛选出附子-半夏抗肿瘤的无毒活性成分及关键靶点，为有效的使用有毒中药，打破有毒中药应用的局限性提供新思路。

Abstract

Objective:

Screen out the antitumor constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma base on system pharmacology with chemical constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma as study objects

in order to provide the theoretical basis for the development of antitumor and nontoxic activities of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma.

Method:

The small molecule ligand library of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma was built based on Traditional Chinese Medicine Systems Pharmacology(TCMSP)

energy of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma was matched with the key protein targets of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signal pathway by molecular docking (SYBYL2.1

Tripos)

the Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma-targets network model was established based on Cytoscape 3.5.1

and the physicochemical properties of the antitumor activity in Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma were predicted by using SwissADME and admetSAR.

Result:

There were 25 small molecule constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma. Through the energy match

key antitumor constituents of Pinelliae Rhizoma were gondoic acid

13-eicosadienoic

baicalin

13-epoxy-9-hydroxynonadeca-7

10-dienoic acid. Key antitumor constituents of Aconiti Lateralis Radix Praeparata were deltoin

sitosterol

neokadsuranic acid B

14-eicosadienoic acid. Phosphatidylinositol 3-kinase (PI3K

)

phosphatase and tensin homolog deleted on chromosome ten (PTEN)

phosphoinositide dependent protein kinase 1 (PDK1) were key antitumor targets of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma. There were 8 key antitumor constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma

which had a low CYP450 inhibition and basically followed the Lipinski rule.

Conclusion:

Antitumor nontoxic constituents of Aconiti Lateralis Radix Praeparata-Pinelliae Rhizoma and key targets are screened out from the molecular level

which provides the new ideas for the effective use of nontoxic traditional Chinese medicine(TCM) and breaks the restrictions in using nontoxic TCM.

关键词

Keywords

references

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