2. Academic Validation
  3. Jujuboside B inhibits febrile seizure by modulating AMPA receptor activity

Jujuboside B inhibits febrile seizure by modulating AMPA receptor activity

  • J Ethnopharmacol. 2023 Mar 25:304:116048. doi: 10.1016/j.jep.2022.116048.
Baohua Jin 1,  Wanjun Bai 2,  Jiaojiao Zhao 1,  Xia Qin 1,  Han Guo 1,  Yahui Li 1,  Jie Hao 1,  Siruan Chen 1,  Zuxiao Yang 1,  Hui Bai 3,  Zongmao Zhao 4,  Qingzhong Jia 5,  Changzheng Dong 6,  Zhuo Huang 7,  Dezhi Kong 8,  Wei Zhang 9
Affiliations

Affiliations

  • 1 Department of Pharmacology, Institution of Chinese Integrative Medicine, Hebei Medical University, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei, 050017, China.
  • 2 Department of Pharmacology, Institution of Chinese Integrative Medicine, Hebei Medical University, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei, 050017, China; Department of Pharmacology, Hebei General Hospital, Shijiazhuang, 050051, China.
  • 3 Department of Cardiac Ultrasound, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050017, China.
  • 4 Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050017, China.
  • 5 Department of Pharmacology, Center for Innovative Drug Research and Evaluation, Institute of Medical Science and Health, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei Province, 050017, China.
  • 6 Department of Neurosurgery, Hebei General Hospital, Shijiazhuang, Hebei, 050017, China.
  • 7 Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 8 Department of Pharmacology, Institution of Chinese Integrative Medicine, Hebei Medical University, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei, 050017, China. Electronic address: [email protected].
  • 9 Department of Pharmacology, Institution of Chinese Integrative Medicine, Hebei Medical University, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei, 050017, China. Electronic address: [email protected].
PMID: 36549370 DOI: 10.1016/j.jep.2022.116048
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 [CA2+]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.

Keywords

AMPA receptor; Febrile seizure; Jujuboside B; Neuronal excitability.

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