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

  
@article{APS10871,
	author = {Yu Wang and Xiao-yun Qiu and Jia-ying Liu and Bei Tan and Fei Wang and Min-juan Sun and Xu-hong Jiang and Xu-ming Ji and Ceng-lin Xu and Yi Wang and Zhong Chen},
	title = {(+)-Borneol enantiomer ameliorates epileptic seizure via decreasing the excitability of glutamatergic transmission},
	journal = {Acta Pharmacologica Sinica},
	volume = {44},
	number = {8},
	year = {2023},
	keywords = {},
	abstract = {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 (10 μM) 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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/10871}
}