基于整合药理学策略的交泰丸治疗糖尿病的潜在机制分析

段灿灿; 吴先; 穆文碧; 杨沙; 陈启洪; 陈宽; 张建永

doi:10.13422/j.cnki.syfjx.20190807

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基于整合药理学策略的交泰丸治疗糖尿病的潜在机制分析

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- 基于整合药理学策略的交泰丸治疗糖尿病的潜在机制分析
- Potential Mechanism of Jiaotaiwan for Diabetes Based on Integrative Pharmacology Method
- 中国实验方剂学杂志 2019年25卷第8期页码：133-140
- 作者机构：
  
  1.遵义医科大学　基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室，贵州　遵义　 563003；
  2.遵义医科大学　药学院，贵州　遵义　 563009
- 作者简介：
  
  段灿灿，硕士，讲师，从事中药复方作用机制研究，E-mail: duancancan2008@126.com
  张建永，博士，副教授，从事中药系统生物学研究，E-mail: zhangjianyong2006@126.com
- 基金信息：
  
  国家自然科学基金项目(81560736;81803838);贵州省教育厅科技拔尖人才支持项目(黔教合KY字[2017]078);贵州省中药管理局课题项目(QZYY-2015-153);遵义医学院硕士启动基金项目(F-726)
- DOI：10.13422/j.cnki.syfjx.20190807
  中图分类号： R2-0;R22;R285.5;R289
- 收稿日期：2018-09-19，
  
  网络出版日期：2019-01-04，
  
  纸质出版日期：2019-04-20
- 稿件说明：
移动端阅览
段灿灿, 吴先, 穆文碧, 等. 基于整合药理学策略的交泰丸治疗糖尿病的潜在机制分析[J]. 中国实验方剂学杂志, 2019,25(8):133-140.

Can-can DUAN, Xian WU, Wen-bi MU, et al. Potential Mechanism of Jiaotaiwan for Diabetes Based on Integrative Pharmacology Method[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(8): 133-140.
段灿灿, 吴先, 穆文碧, 等. 基于整合药理学策略的交泰丸治疗糖尿病的潜在机制分析[J]. 中国实验方剂学杂志, 2019,25(8):133-140. DOI： 10.13422/j.cnki.syfjx.20190807.

Can-can DUAN, Xian WU, Wen-bi MU, et al. Potential Mechanism of Jiaotaiwan for Diabetes Based on Integrative Pharmacology Method[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(8): 133-140. DOI： 10.13422/j.cnki.syfjx.20190807.

摘要

目的：

交泰丸为中医治疗失眠的经典方剂，目前临床采用异病同治理念治疗糖尿病，且有较好的疗效，明确其潜在作用机制具有重要意义。

方法：

该研究基于整合药理学策略及平台(integrative pharmacology platform of traditional Chinese medicine TCMIP)研究交泰丸的作用靶点及机制等，构建其治疗糖尿病的核心靶点网络，进一步对获取靶点进行基因功能及通路富集分析，构建可视化的“交泰丸-活性成分-核心靶点-关键通路”的多层次关联网络。

结果：

共得到交泰丸中活性成分28个。这些成分治疗糖尿病涉及核心靶点187个，包括疾病靶点15个，如精氨酸加压素受体2(vasopressin V2 receptor

AVPR2)，受体活性修饰蛋白1(receptor activity-modifying protein 1

RAMP1)，受体活性修饰蛋白1(receptor activity-modifying protein 3

RAMP3)，胰岛素受体(insulin receptor

INSR)及胰岛素样生长因子受体1(insulin-like growth factor 1 receptor

IGF1R)等；潜在药物靶点71个，如细胞周期蛋白依赖性激酶9 (cyclin-dependent kinase 9

CDK9)，葡萄糖激酶(glucokinase

GCK)，核转录因子-

B抑制剂

(NF-kappa-B inhibitor alpha

NF-

)，核转录因子-

B p100亚型(NF-kappa-B p100 subunit

NFKB2)及缺氧诱导因子1

(hypoxia inducible factor-1 alpha

HIF1

)等。

结论：

交泰丸治疗糖尿病的机制涉及活化腺苷酸环化酶活性、细胞胰高血糖素反应、激活丝裂原活化蛋白激酶(mitogen-activated protein kinase

MAPK)活性、内分泌系统、促性腺激素释放激素(gonadotropin-releasing hormone

GnRH)信号通路、趋化因子及磷脂酰肌醇三激酶-丝氨酸/苏氨酸激酶(phosphatidylinositol 3-kinase-serine/threonine kinases

PI3K-Akt)等生物过程和信号通路等。该研究为深入探讨交泰丸治疗糖尿病的潜在机制提供了科学依据。

Abstract

Objective:

Jiaotaiwan is a classic prescription in traditional Chinese medicine for insomnia. Modern clinical research has proved its anti-diabetes effect by "the same treatment for different diseases" theory

so it is necessary to study its pharmacological mechanism for anti-diabetes effect.

Method:

In this study

the integrative pharmacology platform of traditional Chinese medicine (TCMIP) was used to explore the potential target and mechanism of Jiaotaiwan

and construct its core target network for diabetes. Then the enrich analysis of GO and KEGG on key targets was conducted to build the visual multilayer association network of "Jiaotaiwan-active composition-core target-key pathway" .

Result:

28 active ingredients were obtained from Jiaotaiwan in this study. Its anti-diabetes effect was relevant to 187 core targets

including 15 known disease targets such as vasopressin V2 receptor (AVPR2)

receptor activity-modifying protein 1 (RAMP1)

receptor activity-modifying protein 3 (RAMP3)

insulin receptor (INSR)

and insulin-like growth factor 1 receptor (IGF1R); as well as 71 predictive drug targets such as cyclin-dependent kinase 9 (CDK9)

glucokinase (GCK)

NF-kappa-B inhibitor alpha (NFKBIA)

NF-kappa-B p100 subunit (NFKB2)

and hypoxia inducible factor-1 alpha (HIF1A).

Conclusion:

The anti-diabetes mechanism of Jiaotaiwan may be associated with activation of adenylate cyclase activity

cellular response to glucagon stimulus

activation of mitogen-activated protein kinase (MAPK) activity

endocrine system

gonadotropin-releasing hormone (GnRH) signaling pathway

Chemokine signaling pathway

phosphatidylinositol 3-kinase-serine/threonine kinases (PI3K-Akt) signaling pathway and other related biological processes and pathways. This study provides a scientific evidence for further study of the anti-diabetes mechanism of Jiaotaiwan.

关键词

Keywords

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