Recent Advances in Bioactive Flavonoids-based Nanotherapeutics as Promising Neuroprotectants in Epilepsy

Epilepsy is a prevalent neurological disorder that can be characterized by seizures and can be caused by abnormal electrical impulses in the brain. Various genetic, environmental, age-related, and lifestyle factors are associated with its pathogenesis, which causes neuronal cells to degenerate over time.

Epilepsy often results from an imbalance between excitatory neurotransmitters, such as glutamate, and inhibitory neurotransmitters, such as GABA. Abnormalities in glutamate receptors like N-methyl-D-aspartate (NMDA), and alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) can lead to excessive neuronal excitation, while dysfunctions in GABA receptors can result in insufficient inhibition, both of which can provoke seizures. Additionally, a variety of receptors and pathways like NF-κB, DAPK, Trκb, COX-2, etc. are associated with the expression of epilepsy. This disorder often faces various limitations in treatment with current anti-epileptic drugs (AEDs), such as drug resistance, adverse effects, and high costs. In context, flavonoids exhibit significant neuroprotective properties in epilepsy through various mechanisms such as antioxidant activity, anti-inflammatory effects, neurotransmitter systems, and receptor modulation.

Flavonoids communicate with different signaling pathways and adjust their activities, prompting valuable neuroprotective impacts. Essential flavonoids such as quercetin, rutin, apigenin, luteolin, genistein, fisetin, chrysin, vitexin, naringin, baicalin, catechin, morin, hesperetin, kaempferol, gallic acid, silibinin, wogonin, etc. have shown promising results in channel regulation, reduced oxidative stress and neuroinflammation, and neuronal excitability in experimental models of epilepsy. Given their inherent neuroprotective properties and ability to modulate multiple pathways involved in epilepsy, flavonoids hold considerable promise as multitargeted, accessible, and low-cost alternatives to conventional AEDs. Although there are challenges with target specificity and bioavailability, innovative approaches such as nanotechnology and chemical modifications are being developed to enhance these aspects.

Focusing on the mechanisms of action and neuroprotective benefits the paper highlights the promising role of flavonoids and flavonoid-based nanotherapeutics as a beneficial addition to epilepsy treatment strategies.