Appeal of Urolithins from Synthesis to Biological Activities.

Urolithins (Uros), a series of natural polyphenols derived from ellagic acid through gut bacteria metabolism, have gathered significant attention due to their diverse bioactivities such as maintaining mitochondrial health and anti-inflammatory and antioxidative effects. However, the ability to metabolize Uros varies among individuals. This Review provides a comprehensive insight into the synthesis, encapsulation and bioactivities of Uros, focusing on their biotransformation in vivo. We highlight the critical role of gut microbiota in the biotransformation of urolithins, including primary bacterial species such as Gordonibacter urolithinfaciens, Enterocloster bolteae and Enterococcus faecium. Furthermore, the therapeutic potential of Uros in alleviating neurodegenerative diseases, cancer, and Duchenne muscular dystrophy is discussed. Finally, several encapsulation strategies for enhancing the solubility and bioavailability of Uros are summarized. Future research direction includes identifying key genes involved in Uros biotransformation, elucidating the bioactive mechanisms of Uros, and improving their bioavailability. In conclusion, we synthesized biosynthetic pathways and bioactive properties of Uros for better utilization in health management.