Clinical and Mechanistic Exploration of Ellagic Acid in Neurodegenerative Diseases: Targeted Neuroprotection Through Cellular and Molecular Mechanisms

ABSTRACT Neurodegenerative diseases (NDs) such as Parkinson's, Alzheimer's, and Huntington's diseases are complex due to their intricate pathophysiology and the lack of available treatments. NDs, identified with the loss of neurons and functional impairment, significantly impact global health. Researchers have identified the natural polyphenolic molecule ellagic acid (EA) as a potential neuroprotective agent. This review explores EA's clinical and molecular properties for NDs. It also evaluates its molecular processes, highlighting its antioxidant, antiapoptotic, and anti‐inflammatory properties that support its neuroprotective properties. EA has potent antioxidant properties because it effectively scavenges free radicals and enhances natural antioxidant defenses. It lowers oxidative stress, which is a major contributor to brain damage. It is also prominent for its powerful anti‐inflammatory properties, inhibiting the activation of microglia and astrocytes and decreasing the formation of proinflammatory cytokines. In addition, it reduces the expression of proapoptotic factors and the overexpression of antiapoptotic proteins. EA has effects on neuronal survival and function by regulating signaling pathways such as NF‐κB, Nrf2, and MAPK. It summarizes clinical trials evaluating EA's safety and effectiveness in treating NDs as a potential therapeutic intervention. In addition, it emphasizes the therapeutic potential of EA in treating NDs by integrating molecular insights with clinical findings. Recent clinical research evaluates the safety and therapeutic effectiveness of EA in NDs. The review recommends further research on EA as a potential therapeutic agent, integrating molecular insights with clinical evidence to reduce NDs. Furthermore, it indicates that there are improvements in neuroinflammation reduction, cognitive function enhancement, and overall neuroprotection.