Neuroprotective Role of Flavonoids: Implications for Natural Epilepsy Therapy-A Systematic Review.

INTRODUCTION: Epilepsy is a chronic neurological disorder characterised by recurrent, unprovoked seizures due to abnormal neuronal hyperexcitability and dysfunction. Despite the availability of several Antiepileptic Drugs (AEDs), approximately one-third of epilepsy patients are drugresistant and often experience adverse effects. This has led to the search for plant- derived bioactive compounds such as flavonoids, which have been reported to have widespread neuroprotective effects. This study aims to evaluate the neuroprotective role of flavonoids and their therapeutic implications in the management of epilepsy. MATERIALS AND METHODS: A systematic literature search was conducted on electronic databases such as PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar with PRISMA guidelines. Relevant literature on the neuroprotective effects of flavonoids and their applications in epilepsy was reviewed. Both in vitro and in vivo studies on the anticonvulsant and neuroprotective effects of flavonoids in chemically and electrically induced epilepsy models were analyzed to obtain relevant information on the mechanisms of action and molecular targets of flavonoids, frequency of seizures, neurobehavioral effects, and histopathological effects. RESULTS: The studies clearly demonstrate that flavonoids exert anticonvulsant and neuroprotective effects through multiple mechanisms. These include reducing oxidative stress by enhancing endogenous antioxidant enzymes, suppressing pro-inflammatory cytokines, modulating GABAergic and glutamatergic neurotransmission, inhibiting voltage-gated ion channels, stabilising mitochondrial function, and decreasing apoptotic signalling. Several studies report decreased seizure severity, increased seizure latency, and preservation of hippocampal neuronal integrity following flavonoid administration. DISCUSSION: According to the data compiled in this review, flavonoids have broad-spectrum neuroprotective effects by modulating several molecular targets linked to epileptogenesis. This multitargeted profile may provide benefits above traditional therapies and is consistent with the intricate biology of epilepsy. However, there is little translational and clinical confirmation in the present body of evidence, which is primarily preclinical. Variations hamper standardization and limit comparative analysis of flavonoid content, dosage regimens, and experimental design. Further research is required to establish therapeutic usefulness, particularly regarding bioavailability, pharmacokinetics, and possible drug- herb interactions. CONCLUSION: Flavonoids demonstrate significant multi-target neuroprotective potential in experimental models of epilepsy. This article focuses on various aspects, such as the mechanisms of action and neuroprotective benefits of various flavonoids against epilepsy. The article highlights the promising role of various flavonoids and the potential of nanotherapeutic flavonoids against epilepsy.