Beneficial Role of Natural Polyphenols Against Epilepsy: Greasing the Wheels of Pharmacotherapy Research for Epilepsy

ABSTRACT Epilepsy is the most disabling neurological disease that affects all economic classes, age groups, regions, and races. Although many antiseizure drugs are approved for epilepsy treatment, they fail to work in about 30%–40% of patients. Thus, there is a great need to identify better pharmacological agents to treat epilepsy. Phytochemicals, including alkaloids, flavonoids, polyphenols, and terpenes, may be a promising option, as they have shown remarkable efficacy in alleviating neurological diseases in cellular, preclinical, and clinical studies. Polyphenols, including phenolic acids, flavonoids, lignans, and stilbenes, are abundant in several vegetables, beverages, fruits, and other plant‐derived products, and are gaining importance in the treatment of epilepsy. Polyphenols, alone or in synergy with other medicines, are used to treat epilepsy due to their potent antioxidant and anti‐inflammatory properties, as well as their metal‐ion chelating activities. This review article details the therapeutic potential of plant polyphenols in various preclinical models of epilepsy and epileptogenesis. In this review, we highlight the role of various polyphenols, including curcumin, resveratrol, epigallocatechin‐3‐gallate, naringenin, quercetin, hesperidin, ellagic acid, gallic acid, caffeic acid, proanthocyanidins, and apigenin, that inhibit neuronal damage and the progression of epilepsy. The neuroprotective and antioxidant roles of these natural polyphenols show promise for managing acute seizures and preventing epileptogenesis, as they can modulate signaling molecules of various pathways involved in the pathology of epilepsy. As mixed results were obtained regarding the antiepileptic or antiseizure potential of these molecules, additional mechanism‐based animal studies are required to determine, with greater certainty, the practical use of natural polyphenols in combating epilepsy.