Abstract
Recently, alternative therapies are gaining popularity in the treatment of epilepsy. The present study aimed to find out the antiepileptic potential of quercetin, catechin, and kaempferol. In vivo and in silico experiments were conducted to investigate their therapeutic potential. 25 mg/kg/day of pentylenetetrazole was administered for 4 weeks after epilepsy was induced in the rats; this was followed by the behavioral studies and histological analysis of rat brain slices. Binding affinities of kaempferol, quercetin, and catechin were assessed by performing in silico studies. Kaempferol, quercetin, and catechin were found to have the highest binding affinity with the synaptic vesicle 2A (SV2A) protein, comparable to standard levetiracetam (LEV). The mRNA levels of SV2A, as well as the expression of TNF, IL 6, IL 1 beta, NFkB, IL 1Ra, IL 4, and IL 10, were investigated using qPCR. Our results indicate for the first time that SV2A is also a transporter of understudied phytoflavonoids, due to which a significant improvement was observed in epileptic parameters. The mRNA levels of SV2A were found to be significantly elevated in the PF-treated rats when compared with those of the control rats with epilepsy. Additionally, downregulation of the pro-inflammatory cytokines and upregulation of the anti-inflammatory cytokines were also noted in the PF-treated groups. It is concluded that kaempferol, quercetin, and catechin can effectively decrease the epileptic seizures in our chronic epilepsy rat model to a level that is comparable to the antiepileptic effects induced by levetiracetam drug.
Highlights
Epilepsy is a neurological disorder that is characterized by recurrent malicious seizures, which are varied in occurrence and severity (Szilágyi et al, 2014)
First-generation antiepileptic drugs (AEDs) include: carbamazepine, phenobarbital, and valproic acid, while lamotrigine, vigabatrin, tiagabine, topiramate, gabapentin, and levetiracetam (LEV) are classified as second-generation drugs (Ahmad et al, 2017). These drugs exert their antiepileptic effects by modulating ionotropic glycine amino butyric acid (GABA)-A, glutamate receptors, synaptic vesicle 2 A (SV2A) transporters, and ion channels such as Na+, Ca++, and K+ (Noachtar et al, 2008; Leclercq et al, 2020)
After the in silico studies confirmed the binding of PFs with the SV2A receptor, the in vivo studies were performed in the chronic epilepsy rat model to establish the proof of concept as well as find confirmation of our in silico study
Summary
Epilepsy is a neurological disorder that is characterized by recurrent malicious seizures, which are varied in occurrence and severity (Szilágyi et al, 2014). First-generation AEDs include: carbamazepine, phenobarbital, and valproic acid, while lamotrigine, vigabatrin, tiagabine, topiramate, gabapentin, and levetiracetam (LEV) are classified as second-generation drugs (Ahmad et al, 2017). These drugs exert their antiepileptic effects by modulating ionotropic GABA-A, glutamate receptors, synaptic vesicle 2 A (SV2A) transporters, and ion channels such as Na+, Ca++, and K+ (Noachtar et al, 2008; Leclercq et al, 2020). This eventually results in the fluctuation of the firing properties of neurons (Verrotti et al, 2020). PTZ antagonizes the glycine amino butyric acid (GABA)-A receptor that leads to the development of seizures in rats (Hansen et al, 2004; Badawi et al, 2021)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
