(+)-Borneol enantiomer ameliorates epileptic seizure via decreasing the excitability of glutamatergic transmission  

作　　者：Yu Wang Xiao-yun Qiu Jia-ying Liu Bei Tan Fei Wang Min-juan Sun Xu-hong Jiang Xu-ming Ji Ceng-lin Xu Yi Wang Zhong Chen 

机构地区：[1]Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province,Department of Neurology,The First Affiliated Hospital,School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,310053,China [2]Zhejiang Rehabilitation Medical Center,The Third Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,310061,China [3]Institute of Pharmacology&Toxicology,College of Pharmaceutical Sciences,School of Medicine,Zhejiang University,Hangzhou,310012,China

出　　处：《Acta Pharmacologica Sinica》2023年第8期1600-1611,共12页中国药理学报（英文版）

基　　金：supported by grants from the National Key R&D Program of China (2021ZD0202803 and 2020YFA0803902);the National Natural Science Foundation of China (82022071);the Natural Science Foundation of Zhejiang Province (LD22H310003);the Research Project of Zhejiang Chinese Medical University (2022JKJNTZ13).

摘　　要：Epilepsy is one common brain disorder,which is not well controlled by current pharmacotherapy.In this study we characterized the therapeutic potential of borneol,a plant-derived bicyclic monoterpene compound,in the treatment of epilepsy and elucidated the underlying mechanisms.The anti-seizure potency and properties of borneol were assessed in both acute and chronic mouse epilepsy models.Administration of(+)-borneol(10,30,100 mg/kg,i.p.)dose-dependently attenuated acute epileptic seizure in maximal-electroshock seizure(MES)and pentylenetetrazol(PTZ)-induced seizure models without obvious side-effect on motor function.Meanwhile,(+)-borneol administration retarded kindling-induced epileptogenesis and relieved fully kindled seizures.Importantly,(+)-borneol administration also showed therapeutic potential in kainic acid-induced chronic spontaneous seizure model,which was considered as a drug-resistant model.We compared the anti-seizure efficacy of 3 borneol enantiomers in the acute seizure models,and found(+)-borneol being the most satisfying one with long-term anti-seizure effect.In electrophysiological study conducted in mouse brain slices containing the subiculum region,we revealed that borneol enantiomers displayed different anti-seizure mechanisms,(+)-borneol(10μM)markedly suppressed the high frequency burst firing of subicular neurons and decreased glutamatergic synaptic transmission.In vivo calcium fiber photometry analysis further verified that administration of(+)-borneol(100 mg/kg)inhibited the enhanced glutamatergic synaptic transmission in epilepsy mice.We conclude that(+)-borneol displays broad-spectrum anti-seizure potential in different experimental models via decreasing the glutamatergic synaptic transmission without obvious side-effect,suggesting(+)-borneol as a promising anti-seizure compound for pharmacotherapy in epilepsy.

关 键 词：epilepsy anti-seizure drug (+)-borneol valproate SUBICULUM glutamatergic synaptic transmission 

分 类 号：R285.5[医药卫生—中药学]