Epilepsy: Insights into Pathophysiology, Therapeutic Approaches, and the Emerging Role of Phytochemicals

ABSTRACT: The fourth most common cause of disease burden worldwide is epilepsy. A chronic neurological disorder marked by frequent, unprovoked seizures brought on by aberrant brain electrical activity. It affects more than 60 million people globally, has a significant detrimental impact on patients' life quality, and is linked to comorbid conditions like anxiety, depression, and cognitive impairment. About 30% of patients have drug-resistant epilepsy, which raises death rates and emphasises the need for alternative therapeutic approaches even though there are more than 30 antiepileptic medications (AEDs) that have received USFDA approval. The pathophysiology of epilepsy is examined in this study, with particular attention paid to ion channel dysregulation and neurotransmitter abnormalities, such as glutamate-mediated pathways and γ-aminobutyric acid (GABA). Along with the pharmacological targets and MOA of current AEDs, classification of epilepsy and seizures—including generalised, partial, and status epilepticus forms—is covered. The potential of plant-based phytochemicals as multitarget therapeutic agents is investigated in light of the shortcomings of existing treatments. Preclinical research shows how well these substances work to change important biochemical pathways and receptors, highlighting their potential as supplements or substitutes for traditional AEDs. Clarifying their modes of action, optimizing dosage, and ensuring safety still present difficulties. Given that 80% of epilepsy occurrences occur in low-income areas with limited access to effective treatments, this review highlights the critical need for accessible and reasonably priced therapeutics. Research on phytochemicals offers a viable way to fill up these gaps and could revolutionise the way epilepsy is managed globally. Alkaloids, Phenolics, Terpenoids, Flavonoids like quercetin, kaempferol, and luteolin have shown promise in reducing seizure frequency and protecting against neuronal damage.