Abstract
The anticonvulsive potential of proteins extracted from Orthosiphon stamineus leaves (OSLP) has never been elucidated in zebrafish (Danio rerio). This study thus aims to elucidate the anticonvulsive potential of OSLP in pentylenetetrazol (PTZ)-induced seizure model. Physical changes (seizure score and seizure onset time, behavior, locomotor) and neurotransmitter analysis were elucidated to assess the pharmacological activity. The protective mechanism of OSLP on brain was also studied using mass spectrometry-based label-free proteomic quantification (LFQ) and bioinformatics. OSLP was found to be safe up to 800 µg/kg and pre-treatment with OSLP (800 µg/kg, i.p., 30 min) decreased the frequency of convulsive activities (lower seizure score and prolonged seizure onset time), improved locomotor behaviors (reduced erratic swimming movements and bottom-dwelling habit), and lowered the excitatory neurotransmitter (glutamate). Pre-treatment with OSLP increased protein Complexin 2 (Cplx 2) expression in the zebrafish brain. Cplx2 is an important regulator in the trans-SNARE complex which is required during the vesicle priming phase in the calcium-dependent synaptic vesicle exocytosis. Findings in this study collectively suggests that OSLP could be regulating the release of neurotransmitters via calcium-dependent synaptic vesicle exocytosis mediated by the “Synaptic Vesicle Cycle” pathway. OSLP’s anticonvulsive actions could be acting differently from diazepam (DZP) and with that, it might not produce the similar cognitive insults such as DZP.
Highlights
Epilepsy is a chronic non-communicable disease of the brain that affects around 70 million people of all ages worldwide and accounts for about 1% of the global burden of disease
The OSLP-treated groups, 50, 100, 200, and 400 μg respectively, showed slight preferences for the bottom half of tank when compared to the vehicle control (VC) group (Figure 2b–e)
The OSLP 800 μg group (Figure 2f) showed a similar swimming pattern to the VC group as they swam throughout the whole tank with no apparent preference for any part of the tank
Summary
Epilepsy is a chronic non-communicable disease of the brain that affects around 70 million people of all ages worldwide and accounts for about 1% of the global burden of disease. Epilepsy has a high prevalence and an estimated five million people are diagnosed with epilepsy each year. Epilepsy is characterized by recurrent seizures due to brief disturbances in the electrical functions of the brain. It involves brief episodes of involuntary movement that lead to changes in sensory perception, motor control, behavior, autonomic function, or sometimes loss of consciousness [1].
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