"Behavioral rescue: Naringenin's neuroprotective effects against PTZ-induced seizures by mitigating oxidative stress and neuroinflammation in zebrafish larvae"

Abstract

Epilepsy is a complex neurological disorder affecting approximately 70 million people worldwide, accounting for about 1% of the global population. Despite significant advancements in pharmaceutical therapies, the molecular mechanisms underlying epileptogenesis remain poorly understood, leading to symptomatic treatment being ineffective for about 30% of patients. Recent evidence implicates oxidative stress and neuroinflammation in the pathophysiology of epilepsy. Traditional Chinese Medicine (TCM) has been used for millennia across Asia and beyond to treat conditions such as cancer, cardiovascular disorders, and neurological diseases, owing to its proven effectiveness. Naringenin is a traditional Chinese component commonly found in citrus fruits and is a naturally occurring flavonoid. The present investigation aimed to examine the neuroprotective properties of Naringenin in mitigating PTZ-induced seizures in zebrafish larvae. Zebrafish were administered Naringenin (50 µM) for 24 hours at 6 days post-fertilization (dpf), followed by exposure to 15 mM PTZ for 30 minutes. The study assessed c-fos expression and synaptic activity, oxidative damage, antioxidant defence mechanisms, apoptosis, and levels of nrf2, ho-1, and nqo-1 in the head regions of zebrafish larvae. Additionally, the expression of inflammatory cytokines (cox-2, tnfα, il-1β, and il-6) was evaluated. Naringenin pretreatment restored c-fos expression and synaptic activity in epileptic zebrafish larvae. The study observed high levels of oxidative damage, reduced antioxidant defences, and increased apoptosis in the larvae with epilepsy. Specifically, levels of nrf2, ho-1, and nqo-1 were decreased in the head regions of the epileptic zebrafish larvae. Naringenin administration mitigated oxidative stress, reduced neuronal apoptosis, and increased the expression of nrf2, ho-1, and nqo-1. Additionally, during seizures, inflammatory cytokines such as cox-2, tnfα, il-1β, and il-6 were upregulated, but naringenin pretreatment was shown to mitigate this effect. The findings collectively underscore the potential neuroprotective effects of Naringenin against PTZ-induced seizures. Naringenin modulates behavioural patterns, reduces oxidative stress, and dampens neuroinflammation, highlighting its promise as a therapeutic agent in epilepsy management. The study provides a foundation for further research into the mechanisms by which Naringenin exerts its protective effects and its potential clinical applications in treating epilepsy.

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