Jujuboside B inhibits febrile seizure by modulating AMPA receptor activity. (25th March 2023)

• Record Type: Journal Article
• Authors: Jin, Baohua; Bai, Wanjun; Zhao, Jiaojiao; Qin, Xia; Guo, Han; Li, Yahui; Hao, Jie; Chen, Siruan; Yang, Zuxiao; Bai, Hui; Zhao, Zongmao; Jia, Qingzhong; Dong, Changzheng; Huang, Zhuo; Kong, Dezhi; Zhang, Wei
• Is Part Of: Journal of ethnopharmacology. Volume 304(2023)
• Publication Date: 2023-03-25
• Subjects: Jujuboside B -- Febrile seizure -- AMPA receptor -- Neuronal excitability; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.116048
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Febrile seizure is a common neurologic disorder with limited treatment occurring in infants and children under the age of five. Jujuboside B (JuB) is a main bioactive saponin component isolated from the Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen (ZSS), seed of Ziziphus jujuba Mill, which has been proved to exhibit neuroprotective effects recently. Aim of the study: In this study, we aimed at elucidating the effect of JuB on suppressing febrile seizure and the potential mechanisms. Methods: Electroencephalogram (EEG) recording was used to monitor the severity of febrile seizures. The JuB in the brain was identified by mass spectrometry. Neuronal excitability was investigated using patch clamp. Results: JuB (30 mg/kg) significantly prolonged seizure latency and reduced the severity in hyperthermia-induced seizures model mice. Hippocampal neuronal excitability was significantly decreased by JuB. And JuB significantly reduced the excitatory synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-iso-xazolepropionic acid receptor (AMPAR), including evoked excitatory postsynaptic currents (eEPSCs), and miniature EPSCs (mEPSCs) in hippocampal neurons. Furthermore, JuB also significantly inhibited recombinant GluA1 and GluA2 mediated AMPA current in HEK293 cell and decreased the upregulation of [Ca 2+ ]i induced by AMPA in primary cultured cortex neurons. Conclusions: JuB suppressed the excitability of hippocampal neurons by inhibiting the activity of AMPAR and reducing the intracellular free calcium, thereby relieving febrile seizures. Graphical abstract: Image 1 Highlights: Jujuboside B (JuB) could relieve febrile seizures in mice model. JuB suppressed the excitability of hippocampal neurons. JuB inhibited AMPAR currents, and the synaptic transmission mediated by AMPAR. JuB reduced the intracellular free calcium in cultured primary neuron.