Neuroprotective Potential of Ellagic Acid: A Critical Review

Abstract

ABSTRACT Ellagic acid (EA) is a dietary polyphenol present in various fruits, vegetables, herbs, and nuts. It exists either independently or as part of complex structures, such as ellagitannins, which release EA and several other metabolites including urolithins following absorption. During the past few decades, EA has drawn considerable attention because of its vast range of biological activities as well as its numerous molecular targets. Several studies have reported that the oxidative stress–lowering potential of EA accounts for its broad-spectrum pharmacological attributes. At the biochemical level, several mechanisms have also been associated with its therapeutic action, including its efficacy in normalizing lipid metabolism and lipidemic profile, regulating proinflammatory mediators, such as IL-6, IL-1β, and TNF-α, upregulating nuclear factor erythroid 2-related factor 2 and inhibiting NF-κB action. EA exerts appreciable neuroprotective activity by its free radical–scavenging action, iron chelation, initiation of several cell signaling pathways, and alleviation of mitochondrial dysfunction. Numerous in vivo studies have also explored the neuroprotective attribute of EA against various neurotoxins in animal models. Despite the increasing number of publications with experimental evidence, a critical analysis of available literature to understand the full neuroprotective potential of EA has not been performed. The present review provides up-to-date, comprehensive, and critical information regarding the natural sources of EA, its bioavailability, metabolism, neuroprotective activities, and underlying mechanisms of action in order to encourage further studies to define the clinical usefulness of EA for the management of neurological disorders.