Insights Into Effects of Ellagic Acid on the Nervous System: A Mini Review

Multiple lines of evidence suggest that disease-related neurodegeneration seems to be a multifactorial process that involves different cytotoxic pathways converging in cell death. Neuropathological evidence indicates that neuroinflammation, excitotoxicity, redox-active metals, increased reactive oxygen and nitrogen species, abnormalities in the activity of the ubiquitin-proteasome system, impairments in endogenous antioxidant defense mechanisms, mitochondrial dysfunction, as well as a reduction in the expression of trophic factors in neuronal tissues might play a role in the pathobiology of disease. In addition, increased expression of proapoptotic proteins, which leads to neuronal cell death, plays an important role in the onset and progression of neurodegeneration. With respect to the inefficacy of single-target drugs for the treatment of numerous neurodegenerative disorders, much attention has been paid to natural products with pluripharmacological properties as well as negligible adverse effects. Ellagic acid is known as an important natural phenolic antioxidant, that is widely found in different fruits and vegetables. Recent studies have shown that ellagic acid may invoke a spectrum of cell signaling pathways to attenuate or slow down the development of neurodegenerative disorders. Ellagic acid possesses potent neuroprotective effects through its free radical scavenging properties, iron chelation, activation of different cell signaling pathways, and mitigation of mitochondrial dysfunction. The aim of this review is to critically summarize and analyze the available literature regarding the neuroprotective effects of ellagic acid with emphasis on its molecular mechanisms of action. In addition, we also discuss the biosynthesis, sources, bioavailability, and metabolism, of ellagic acid to provide as accurately as possible the much needed information for assessment of the overall protective effects of this compound in the central nervous system.