ISSN 1674-3865  CN 21-1569/R
主管：国家卫生健康委员会
主办：中国医师协会
　　　辽宁省基础医学研究所
　　　辽宁中医药大学附属医院
中国中西医结合儿科学

中国中西医结合儿科学 ›› 2021, Vol. 13 ›› Issue (5): 436-443.

• 小儿中药应用研究 • 上一篇    下一篇

基于网络药理学探讨半夏厚朴药对治疗癫痫的作用机制研究

目的:探究半夏厚朴药对治疗癫痫的有效成分和作用机制，为临床癫痫的治疗提供理论依据。
方法:采用TCMSP数据库筛选半夏和厚朴的有效成分及其作用靶点；利用STRING数据库构建蛋白互作网络图并筛选半夏-厚朴药对治疗癫痫的核心靶点；通过DAVID数据库进行KEGG信号通路和生物过程富集分析；利用Cytoscape软件构建“有效成分-关键靶点通路”网络图；采用MOE对接模块的半柔性对接模块进行分子对接验证。
结果:本研究共收集到半夏和厚朴的化学成分共259个，共发现10个潜在有效成分作用于与癫痫相关的55个靶点和10条主要代谢通路。结果表明，半夏-厚朴药对可通过多个有效成分如黄芩素、黄芩苷和松柏苷等，多条通路如过氧化物酶体增殖物激活受体（PPAR）、类固醇激素生物合成和花生四烯酸代谢等，多个靶点如PPARA、PPARD和PPARG等降低神经元异常放电，减少癫痫发作。分子对接结果显示，癫痫治疗的代表性靶点PPAR与其对应的10个潜在有效成分均有良好的结合活性。
结论:半夏-厚朴在治疗癫痫方面呈现多成分、多靶点、多通路的特点，其有效成分通过与癫痫发生发展相关的多个靶点蛋白作用，调控多条生物通路，起到相须相使、协同增效的作用。本研究为半夏-厚朴药对药效成分挖掘、作用机制探究及临床合理使用提供了研究基础。   

  1. 519041 广东 珠海，遵义医科大学珠海校区生物工程系（杨燕，汪泽，曹永军，王朝群，何希瑞），基础医学部（任娟）
  • 出版日期:2021-10-25 发布日期:2021-12-06
  • 通讯作者: 何希瑞，E-mail:xiruihe6105194@163.com
  • 作者简介:杨燕（1983-），女，医学硕士，助理实验师。研究方向：中药药理学研究
  • 基金资助:
    遵义市科技计划项目青年人才专项［遵市科合HZ字（2020）78号］；遵义医学院学术新苗培养及创新探索专项基金（［2017］5733-038，［2018］5772-074，［2019］-017］）；遵义市科技计划项目［（2018）21］

Investigating the mechanism of Pinellia ternata-Mangnolia officinalis pair for epilepsy via network pharmacology

Objective:To investigate the active components and potential molecular mechanism of Pinellia ternata-Mangnolia officinalis pair in the treatment of epilepsy, and to provide a theoretical basis for clinical treatment of epilepsy. #br# Methods:The active components and their targets of P. ternata and M. officinalis were screened via the traditional Chinese medicine systems pharmacology platform(TCMSP) and therapeutic targets database. The protein interaction network was constructed with the STRING database to screen for core targets of P. ternata and M. officinalis in the treatment of epilepsy. The interactive active network map of "active component-keytarget-pathway" was constructed with Cytoscape software. Biological process and KEGG signal pathway enrichment analysis was performed by DAVID database. Finally, docking of the representative -active components with the core target of epilepsy was carried out using MOE software.#br# Results:Two hundred and fifty-nine components of P. ternata and M. officinalis were obtained. Data analysis showed that ten active components of P. ternataM. officinalis pair were identified, which acted on fifty-five potential targets as well as ten pathways related to epilepsy. Herb-component-target-pathway network analysis showed that baicalein, baicalin and coniferin, etc. were the main active components. These active components interacted with multiple targets and affected various biological pathways to reduce the abnormal electrical discharge of neurons and decrease the frequency of seizure. The targets involved in the treatment of epilepsy included PPARA, PPARD and PPARG, and the pathways included PPAR signaling, steroid hormone biosynthesis and arachidonic acid metabolism. Molecular docking results showed that PPAR, a representative target for the treatment of epilepsy, had good binding activity with these ten potential active components.#br# Conclusion:The active components of P. ternata-M. officinalis pair regulate multiple biological pathways by regulating and interacting with multiple target proteins related to the occurrence and development of epilepsy, showing the characteristics of being multi-component, multi-target and multiple biological pathways. The present study provides a research basis for the exploration of the active components P. ternata-M. officinalis pair, the study of mechanism of action and clinical rational use of this herb pair in future.   

  1. Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China
  • Online:2021-10-25 Published:2021-12-06

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摘要： 目的:探究半夏厚朴药对治疗癫痫的有效成分和作用机制，为临床癫痫的治疗提供理论依据。
方法:采用TCMSP数据库筛选半夏和厚朴的有效成分及其作用靶点；利用STRING数据库构建蛋白互作网络图并筛选半夏-厚朴药对治疗癫痫的核心靶点；通过DAVID数据库进行KEGG信号通路和生物过程富集分析；利用Cytoscape软件构建“有效成分-关键靶点通路”网络图；采用MOE对接模块的半柔性对接模块进行分子对接验证。
结果:本研究共收集到半夏和厚朴的化学成分共259个，共发现10个潜在有效成分作用于与癫痫相关的55个靶点和10条主要代谢通路。结果表明，半夏-厚朴药对可通过多个有效成分如黄芩素、黄芩苷和松柏苷等，多条通路如过氧化物酶体增殖物激活受体（PPAR）、类固醇激素生物合成和花生四烯酸代谢等，多个靶点如PPARA、PPARD和PPARG等降低神经元异常放电，减少癫痫发作。分子对接结果显示，癫痫治疗的代表性靶点PPAR与其对应的10个潜在有效成分均有良好的结合活性。
结论:半夏-厚朴在治疗癫痫方面呈现多成分、多靶点、多通路的特点，其有效成分通过与癫痫发生发展相关的多个靶点蛋白作用，调控多条生物通路，起到相须相使、协同增效的作用。本研究为半夏-厚朴药对药效成分挖掘、作用机制探究及临床合理使用提供了研究基础。

关键词: 癫痫, 半夏厚朴药对, 靶点预测, 网络药理学, 有效成分, 分子对接

Abstract: Objective:To investigate the active components and potential molecular mechanism of Pinellia ternata-Mangnolia officinalis pair in the treatment of epilepsy, and to provide a theoretical basis for clinical treatment of epilepsy. 
Methods:The active components and their targets of P. ternata and M. officinalis were screened via the traditional Chinese medicine systems pharmacology platform(TCMSP) and therapeutic targets database. The protein interaction network was constructed with the STRING database to screen for core targets of P. ternata and M. officinalis in the treatment of epilepsy. The interactive active network map of "active component-keytarget-pathway" was constructed with Cytoscape software. Biological process and KEGG signal pathway enrichment analysis was performed by DAVID database. Finally, docking of the representative -active components with the core target of epilepsy was carried out using MOE software.
Results:Two hundred and fifty-nine components of P. ternata and M. officinalis were obtained. Data analysis showed that ten active components of P. ternataM. officinalis pair were identified, which acted on fifty-five potential targets as well as ten pathways related to epilepsy. Herb-component-target-pathway network analysis showed that baicalein, baicalin and coniferin, etc. were the main active components. These active components interacted with multiple targets and affected various biological pathways to reduce the abnormal electrical discharge of neurons and decrease the frequency of seizure. The targets involved in the treatment of epilepsy included PPARA, PPARD and PPARG, and the pathways included PPAR signaling, steroid hormone biosynthesis and arachidonic acid metabolism. Molecular docking results showed that PPAR, a representative target for the treatment of epilepsy, had good binding activity with these ten potential active components.
Conclusion:The active components of P. ternata-M. officinalis pair regulate multiple biological pathways by regulating and interacting with multiple target proteins related to the occurrence and development of epilepsy, showing the characteristics of being multi-component, multi-target and multiple biological pathways. The present study provides a research basis for the exploration of the active components P. ternata-M. officinalis pair, the study of mechanism of action and clinical rational use of this herb pair in future.

Key words: Epilepsy, Pinellia ternata-Mangnolia officinalis pair, Target prediction, Network pharmacology, Active ingredients, Molecular docking