Urolithins: Promising nutritional interventions for mild cognitive impairment

Urolithins, a class of metabolites produced by the gut microbiota from dietary ellagic acid and ellagitannins, are abundant in various medicinal plants and foods, such as the formulation triphala, pomegranates, walnuts, and strawberries. Among them, urolithin A and urolithin B are the most abundant and have been the most extensively studied for their biological activities. The rising number of mild cognitive impairment (MCI) cases emphasizes the critical need for discovering effective strategies to prevent or address the initial stages of cognitive decline. It is especially essential to investigate and explore novel potential alternatives for intervention. This review is among the first to systematically consolidate evidence on the benefits of urolithins across diverse non-Alzheimer's disease MCI models, including schizophrenia-like and sleep deprivation models, with a particular emphasis on the critical translational challenge of individual metabotype variation. Urolithins exhibited considerable promise as potential nutritional interventions for MCI, highlighting the need for further research, especially clinical trials, to fully explore their therapeutic benefits. The main mechanisms through which urolithins may protect against MCI involve the modulation of oxidative stress, neuroinflammation, mitochondrial function, gut microbiota, and the inhibition of cholinesterase and monoamine oxidase. In summary, urolithins have demonstrated promising potential as nutritional interventions for MCI due to their pleiotropic bioactive properties. Certainly, additional studies are essential to comprehensively assess the safety profile and pharmacokinetics of urolithins in the human body. Such research is crucial for evaluating the long-term safety, effectiveness, and overall therapeutic potential of urolithins as possible treatments for MCI. • Urolithins are gut-microbiota metabolites from various medicinal plants and foods. • This review first consolidates evidence on urolithins in non-AD MCI models. • Potential mechanisms include reducing oxidative stress and neuroinflammation. • They also affect mitochondrial function, gut microbiota, and inhibit key enzymes. • Highlighted as novel nutritional strategies, supporting cognitive health.