Identification of Guaifenesin-Andrographolide as a Novel Combinatorial Drug Therapy for Epilepsy Using Network Virtual Screening and Experimental Validation
机构：[1]State Key Laboratory of Bioreactor Engineering, Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.[2]CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.[3]Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from West Yunnan, College of Pharmacy, Dali University, Dali 671000, China.[4]Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200092, China.[5]Key Laboratory of Tropical Biological Resources of Ministry of Education, College of Pharmacy, Hainan University, Haikou 570228, Hainan, China.
Combinatorial drug therapy has attracted substantial attention as an emerging strategy for the treatment of diseases with complex pathological mechanisms. We previously developed a potentially universal computational screening approach for combination drugs and used this approach to successfully identify some beneficial combinations for the treatment of heart failure. Herein, this screening approach was used to identify novel combination drugs for the treatment of epilepsy in an approved drug library. The combination of guaifenesin-andrographolide was first discovered as a promising therapy with synergistic anticonvulsant activities in maximal electroshock (MES)- and subcutaneous pentylenetetrazol (sc-PTZ)-induced epilepsy models in vivo. The studies of network analysis, fluorescence imaging, and N-methyl-d-aspartate (NMDA)-induced cytotoxicity further revealed that guaifenesin-andrographolide might synergistically affect NMDA receptors and then alleviate the pathogenesis of epilepsy. Therefore, we report that the combination of guaifenesin-andrographolide exerts effects against epilepsy through a novel synergistic mechanism and is thus a potential treatment for epilepsy, providing a promising mechanism for the design of novel combinatorial drug treatments against epilepsy.
基金：
This work was supported by the National Natural Science
Foundation of China (82104068, 22107030, 22037002,
81872747, and 81825021), the Innovative Research Team of
Highlevel Local Universities in Shanghai, the National Special
Fund for State Key Laboratory of Bioreactor Engineering
(2060204), Innovation Program of Shanghai Municipal
Education Commission (2021-01-07-00-02-E00104), and
Shanghai Frontier Science Research Base of Optogenetic
Techniques for Cell Metabolism (2021 Sci & Tech 03 28).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|3 区医学
小类|3 区神经科学3 区药物化学3 区生化与分子生物学
最新[2023]版：
大类|3 区医学
小类|3 区生化与分子生物学3 区药物化学3 区神经科学
第一作者：
第一作者机构：[1]State Key Laboratory of Bioreactor Engineering, Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Bioreactor Engineering, Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.[2]CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.[3]Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from West Yunnan, College of Pharmacy, Dali University, Dali 671000, China.[4]Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200092, China.[5]Key Laboratory of Tropical Biological Resources of Ministry of Education, College of Pharmacy, Hainan University, Haikou 570228, Hainan, China.[*1]CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China[*2]State Key Laboratory of Bioreactor Engineering, Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China[*3]Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from West Yunnan, College of Pharmacy, Dali University, Dali 671000, China[*4]Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200092, China[*5]Key Laboratory of Tropical Biological Resources of Ministry of Education, College of Pharmacy, Hainan University, Haikou 570228 Hainan, China
推荐引用方式(GB/T 7714)：
Huang Yunyuan,Xu Haiyan,Wang Pei,et al.Identification of Guaifenesin-Andrographolide as a Novel Combinatorial Drug Therapy for Epilepsy Using Network Virtual Screening and Experimental Validation[J].ACS chemical neuroscience.2022,13(7):978-986.doi:10.1021/acschemneuro.1c00774.
APA：
Huang Yunyuan,Xu Haiyan,Wang Pei,Gu Rurong,Li Xiaokang...&Li Jian.(2022).Identification of Guaifenesin-Andrographolide as a Novel Combinatorial Drug Therapy for Epilepsy Using Network Virtual Screening and Experimental Validation.ACS chemical neuroscience,13,(7)
MLA：
Huang Yunyuan,et al."Identification of Guaifenesin-Andrographolide as a Novel Combinatorial Drug Therapy for Epilepsy Using Network Virtual Screening and Experimental Validation".ACS chemical neuroscience 13..7(2022):978-986
