Molecular Docking of Volatile Oily Constituents of Chinese Herbal Medicine Asari Radix et Rhizoma and CYP1A2 Enzyme

Qiao YU; Yu-hong CHEN; Hui JU; Rui SHEN; Xiao-di KOU; Ai-hong YANG

doi:10.13422/j.cnki.syfjx.20200506

您当前的位置：

首页 >

文章列表页 >

Molecular Docking of Volatile Oily Constituents of Chinese Herbal Medicine Asari Radix et Rhizoma and CYP1A2 Enzyme

Pharmacy Fundamentals | 更新时间：2021-02-09

- Molecular Docking of Volatile Oily Constituents of Chinese Herbal Medicine Asari Radix et Rhizoma and CYP1A2 Enzyme
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 9, Pages: 202-207(2020)
- 作者机构：
  
  天津中医药大学　中药学院，天津　 301617
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20200506
  CLC： R2-0; R22; R285.5
- Received：18 August 2019，
  
  Published Online：19 November 2019，
  
  Published：05 May 2020
- 稿件说明：
移动端阅览
Qiao YU, Yu-hong CHEN, Hui JU, et al. Molecular Docking of Volatile Oily Constituents of Chinese Herbal Medicine Asari Radix et Rhizoma and CYP1A2 Enzyme[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(9): 202-207.
DOI：

Qiao YU, Yu-hong CHEN, Hui JU, et al. Molecular Docking of Volatile Oily Constituents of Chinese Herbal Medicine Asari Radix et Rhizoma and CYP1A2 Enzyme[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(9): 202-207. DOI： 10.13422/j.cnki.syfjx.20200506.

摘要

目的：

研究细辛中黄樟醚、肉豆蔻醚、甲基丁香酚、细辛脑四种挥发油成分以及黄樟醚活性中间体和肉豆蔻醚活性中间体同CYP1A2酶的作用方式。

方法：

通过“Cocktail”探针底物法筛选细辛挥发油成分对CYP1A2，CYP2D6，CYP2E1，CYP3A4和CYP2C19 5种人肝微粒体酶的抑制作用。采用半柔性分子对接的方式研究挥发油成分及中间体与CYP1A2酶的结合能力。

结果：

结果表明挥发油成分对CYP1A2具有较强的抑制作用。分子对接评分结果分别为3.048 7 kcal·mol

-1

(黄樟醚)，6.016 4 kcal·mol

-1

(肉豆蔻醚)，16.969 2 kcal·mol

-1

(甲基丁香酚)，16.013 8 kcal·mol

-1

(细辛脑)，23.923 3 kcal·mol

-1

(黄樟醚活性中间体)和25.594 3 kcal·mol

-1

(肉豆蔻醚活性中间体)。

结论：

分子对接结果表明黄樟醚中间体和肉豆蔻醚中间体与CYP1A2酶的结合能力最强。进一步确定了黄樟醚和肉豆蔻醚是CYP1A2酶的基于机制性抑制剂，与本课题组前期的IC

-shift及谷胱甘肽捕获实验的结果一致。

Abstract

Objective:

To study the mechanisms of action of four volatile oil components (safrole

myristicin

methyleugenol and asarone) and the reactive metabolites of safrole and myristicin with CYP1A2.

Method:

The inhibitory effects of the volatile oil components of Asari Radix et Rhizoma on the human liver microsomal enzymes CYP1A2

CYP2D6

CYP2E1

CYP3A4 and CYP2C19 were screened by the " Cocktail" probe substrate method. The ability of the volatile oil components and intermediates in binding to CYP1A2 enzyme was studied by means of semi-flexible molecular docking.

Result:

The screening results showed that the components had a strong inhibitory effect on CYP1A2.Molecular docking scores were 3.048 7 kcal·mol

-1

(safrole)

6.016 4 kcal·mol

-1

(myristicin)

16.969 2 kcal·mol

-1

(methyleugenol)

16.013 8 kcal·mol

-1

(asarone)

23.923 3 kcal·mol

-1

(safrole reactive metabolites) and 25.594 3 kcal·mol

-1

(myristicin reactive metabolites).

Conclusion:

Molecular docking results indicate that safrole metabolic intermediate and myristicin metabolic intermediate have the strongest ability in binding to CYP1A2 enzyme. This study further confirms that safrole and myristicin are the mechanism-based inhibitors of CYP1A2 enzyme

which is consistent with the results of previous IC

-shift and glutathione capture experiments.

关键词

Keywords

references

丁香，赵万秋，蔡林．中药细辛的现代临床应用研究 [J]．临床合理用药杂志， 2015 , 8 ( 30 ): 177 - 179 .

李明，周强，杨丽娜，等．基于历代中医文献的细辛证治规律与常用剂量探索 [J]. 中国实验方剂学杂志， 2018 , 24 ( 8 ): 23 - 28 .

M JOHANNA , B OLUSHEYI , G C KITE , et al . Medicinally used asarum species: high-resolution LC-MS analysis of aristolochic acid analogs and in vitro toxicity screening in HK-2 cells [J]. Front Pharmacol , 2017 , 8 ( 215 ): 1 - 9 .

高皓，贾党生，郝俊霞，等．基于网络分析细辛毒理学 [J]．中国实验方剂学杂志， 2019 , 25 ( 10 ): 180 - 187 .

陈成伟 . 药物性肝损伤的研究进展及我国存在的问题 [J]．临床肝胆病杂志， 2018 , 34 ( 6 ): 10 - 14 .

K T SUK , D J KIM . Drug-induced liver injury: present and future [J]. Clin Mol Hepatol , 2012 , 18 ( 3 ): 249 - 257 .

E S BJORNSSON , O M BERGMANN , H K BJORNSSON , et al . Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of iceland [J]. Gastroenterology , 2013 , 144 ( 7 ): 1419 - 1425 .

C ZHANG , F CHENG , W LI , et al . In silico prediction of drug induced liver toxicity using substructure pattern recognition method [J]. Mol Inform , 2016 , 35 ( 3/4 ): 136 - 144 .

J HADEM , F TACKE , T BRUNS , et al . Etiologies and outcomes of acute liver failure in Germany [J]. Clin Gastroenterol H , 2012 , 10 ( 6 ): 664 - 669 .

H K HO , J C Y CHAN , K D HARDY , et al . Mechanism-based inactivation of CYP450 enzymes: a case study of lapatinib [J]. Drug Metab Rev , 2015 , 47 ( 1 ): 21 - 28 .

N TAKAHASHI , SUBEHAN , S KADOTA . Mechanism-based CYP2D6 inactivation by acridone alkaloids of Indonesian medicinal plant Lunasia amara [J]. Fitoterapia , 2012 , 83 ( 4 ): 774 - 779 .

郝俊霞，高梓森，高皓，等．基于网络药理学的雷公藤肾毒性机制探讨 [J]．中国实验方剂学杂志， 2019 , 25 ( 16 ): 142 - 151 .

S Y HUANG , Y Q ZOU . Advances and challenges in protein-ligand docking [J]. Int J Mol Sci , 2010 , 11 ( 8 ): 3016 - 3034 .

汪祺，王亚丹，杨建波，等．基于分子对接及体外抑制实验预测芹菜素潜在药物相互作用 [J]．中国中药杂志， 2019 ， 44 ( 18 )： 4043 - 4047 .

雒银珍，赵博文，陈茜，等．基于分子模拟技术的豨莶通栓制剂调脂作用机制及剂型选择研究 [J]．中国中药杂志， 2019 ， 44 ( 7 )： 1436 - 1441 .

E FONTANA , P M DANSETTE , S M POLI . Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity [J]. Curr Drug Metab , 2005 , 6 ( 5 ): 413 - 454 .

A H YANG , X HE , J X CHEN , et al . Identification and characterization of reactive metabolites in myristicin-mediated mechanism-based inhibition of CYP1A2 [J]. Chem Biol Interact , 2015 , 237 : 133 - 140 .

A H YANG , L ZHANG , D X ZHI , et al . Identification and analysis of the reactive metabolites related to the hepatotoxicity of safrole [J]. Xenobiotica , 2018 , 48 ( 11 ): 1164 - 1172 .

李曼华，孙昊鹏，尤启冬 . CYP1A2抑制剂预测模型的建立及评价 [J]．中国药科大学学报， 2013 , 44 ( 5 ): 401 - 409 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway

Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure

Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity

Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics

Screening of Anti-breast Cancer Active Ingredients in Famous Classical Formula Yanghetang

Related Author

HE Junhui

JIA Chunlian

LAI Kedao

ZHOU Guili

ZHOU Rongfei

LI Yi

LI Dongmei

XIE Jiaxiu

Related Institution

Key Laboratory of Chemistry and Engineering of Forest Products， National Ethnic Affairs Commission， Guangxi Key Laboratory of Chemistry and Engineering of Forest Products/Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products， School of Chemistry and Chemical Engineering， Guangxi Minzu University

Guangxi Key Laboratory of Chinese Medicine Quality Standard， Guangxi Institute of Chinese Medicine and Pharmaceutical Science

Guangxi Medical University

State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs， Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences

Jiangxi Province Key Laboratory of Traditional Chinese Medicine（TCM） Pharmacology，Institute of TCM Health Industry，China Academy of Chinese Medical Sciences

AI问答

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰