title: Saikosaponin a mediates the anticonvulsant properties in the HNC models of AE and SE by inhibiting NMDA receptor current and persistent sodium current.
abstract: Epilepsy is one of the most common neurological disorders, yet its treatment remains unsatisfactory. Saikosaponin a (SSa), a triterpene saponin derived from Bupleurum chinensis DC., has been demonstrated to have significant antiepileptic activity in a variety of epilepsy models in vivo. However, the electrophysiological activities and mechanisms of the antiepileptic properties of SSa remain unclear. In this study, whole-cell current-clamp recordings were used to evaluate the anticonvulsant activities of SSa in the hippocampal neuronal culture (HNC) models of acquired epilepsy (AE) and status epilepticus (SE). Whole-cell voltage-clamp recordings were used to evaluate the modulation effects of SSa on NMDA-evoked current and sodium currents in cultured hippocampal neurons. We found that SSa effectively terminated spontaneous recurrent epileptiform discharges (SREDs) in the HNC model of AE and continuous epileptiform high-frequency bursts (SE) in the HNC model of SE, in a concentration-dependent manner with an IC(50) of 0.42 µM and 0.62 µM, respectively. Furthermore, SSa significantly reduced the peak amplitude of NMDA-evoked current and the peak current amplitude of I(NaP). These results suggest for the first time that the inhibitions of NMDA receptor current and I(NaP) may be the underlying mechanisms of SSa's anticonvulsant properties, including the suppression of SREDs and SE in the HNC models of AE and SE. In addition, effectively abolishing the refractory SE implies that SSa may be a potential anticonvulsant candidate for the clinical treatment of epilepsy.
authors.affiliation: Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guang Zhou, People's Republic of China.
authors.forename: Yun-Hong
authors.initials: YH
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Yong
authors.initials: Y
authors.lastname: Bao
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Li
authors.forename: San-Jue
authors.initials: SJ
authors.lastname: Hu
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Xing
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002478:Cells, Cultured; D004594:Electrophysiology; D004827:Epilepsy / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D016194:Receptors, N-Methyl-D-Aspartate; D012503:Saponins; D009828:Oleanolic Acid; D012964:Sodium; C025759:saikosaponin D