Urolithin A and its dietary precursors: mechanisms underlying the improvement of cognitive dysfunction

Cognitive dysfunction, driven by psychiatric and functional factors, toxic factors, neurodegenerative diseases and cerebrovascular diseases, metabolic diseases, and other systemic diseases, represents a significant global health challenge with limited pharmacological interventions. Emerging evidence highlights Urolithin A (UroA)-a gut microbiota-derived polyphenol of dietary ellagitannins (ETs) and ellagic acid (EA) -as a highly promising neuroprotective candidate. Current research has found that UroA and its derivatives have an effect against cognitive dysfunction. However, there is currently a lack of comprehensive reviews. This review provides a comprehensive insight of aetiology and pathogenesis of cognitive dysfunction, with a specific focus on how UroA and its precursors intercept these pathological trajectories, while evaluating the source and metabolism of Urolithin A. And we deeply dissect its mechanisms against cognitive dysfunction, particularly its capacity to mitigate neuroinflammation, restore autophagy, modulate the gur-brain axis and so on. Moreover, we address current knowledge gaps and focus on future perspectives.