文献类型：期刊文献

英文题名：Identification of Guaifenesin-Andrographolide as a Novel Combinatorial Drug Therapy for Epilepsy Using Network Virtual Screening and Experimental Validation

作者：Huang, Yunyuan[1];Xu, Haiyan[2];Wang, Pei[2];Gu, Rurong[2];Li, Xiaokang[1];Xu, Yixiang[1];Wang, Jiqun[1];Qiao, Sicong[1];Shi, Donglei[1];Gao, Zhaobing[2];Li, Jian[1,3,4,5]

机构：[1]East China Univ Sci & Technol, Shanghai Frontier Sci Res Base Optogenet Tech Cel, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Pharm,State Key Lab Bioreactor Engn,Shanghai, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China;[3]Dali Univ, Yunnan Key Lab Screening & Res Anti Pathogen Plan, Coll Pharm, Dali 671000, Peoples R China;[4]Tongji Univ, Clin Med Sci & Tech Innovat Ctr, Shanghai Peoples Hosp 10, Sch Med, Shanghai 200092, Peoples R China;[5]Hainan Univ, Coll Pharm, Minist Educ, Key Lab Trop Biol Resources, Haikou 570228, Hainan, Peoples R China

年份：2022

卷号：13

期号：7

起止页码：978

外文期刊名：ACS CHEMICAL NEUROSCIENCE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000785794700011)】；

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：英文

外文关键词：epilepsy; combination drug; anticonvulsant activity; synergistic mechanism; guaifenesin; andrographolide

摘要：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 druglibrary. The combination of guaifenesin-andrographolide wasfirst discovered as a promising therapy with synergistic anticonvulsantactivities in maximal electroshock (MES)- and subcutaneous pentylenetetrazol (sc-PTZ)-induced epilepsy models in vivo. Thestudies of network analysis,fluorescence imaging, andN-methyl-D-aspartate (NMDA)-induced cytotoxicity further revealed thatguaifenesin-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