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

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

Automated summary

Combinatorial drug therapy is an emerging strategy for the treatment of diseases with complex pathological mechanisms. In this study, a computational screening approach was used to identify novel combination drugs for the treatment of epilepsy. The combination of guaifenesin-andrographolide was found to have synergistic anticonvulsant activities and alleviate the pathogenesis of epilepsy by affecting NMDA receptors.