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Jujuboside B inhibits febrile seizure by modulating AMPA receptor activity
Baohua Jin1, Wanjun Bai2, Jiaojiao Zhao1
1Department 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.
Insights
Jujuboside B (JuB) effectively suppresses febrile seizures in mice by reducing neuronal excitability and inhibiting alpha-amino-3-hydroxy-5-methyl-4-iso-xazolepropionic acid receptor (AMPAR) activity, offering a potential new treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Traditional Chinese Medicine
Background:
- Febrile seizures are common in young children and have limited treatment options.
- Jujuboside B (JuB), a saponin from Ziziphi Spinosae Semen (ZSS), exhibits neuroprotective properties.
Purpose of the Study:
- To investigate the anticonvulsant effects of JuB on febrile seizures.
- To elucidate the underlying mechanisms of JuB's action on neuronal excitability.
Main Methods:
- Electroencephalogram (EEG) was used to monitor seizure activity in a hyperthermia-induced seizure model in mice.
- Patch clamp electrophysiology assessed neuronal excitability and synaptic transmission in hippocampal neurons.
- Mass spectrometry identified JuB in brain tissue.
Main Results:
- JuB (30 mg/kg) significantly increased seizure latency and reduced seizure severity.
- JuB decreased hippocampal neuronal excitability by inhibiting alpha-amino-3-hydroxy-5-methyl-4-iso-xazolepropionic acid receptor (AMPAR) mediated excitatory synaptic transmission.
- JuB inhibited AMPA-induced currents and intracellular calcium increase in neurons.
Conclusions:
- JuB suppresses febrile seizures by reducing hippocampal neuronal excitability.
- Inhibition of AMPAR activity and subsequent reduction in intracellular calcium are key mechanisms.
- JuB shows promise as a therapeutic agent for febrile seizures.
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.
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