# Functional Food-Derived Urolithins: Molecular Mechanisms, Health Effects, and Interactomics with Proteins and Extracellular Vesicles

## TL;DR

This review explores urolithins, metabolites from plant foods, focusing on how they are made, transported, and their health benefits like anti-inflammatory effects.

## Contribution

The paper provides a comprehensive review of urolithin biosynthesis, transport mechanisms, and novel therapeutic applications via extracellular vesicles.

## Key findings

- Urolithins bind to serum albumin for transport and exhibit anti-inflammatory and antioxidant effects.
- Urolithins can be packaged into extracellular vesicles, suggesting new transport and therapeutic mechanisms.
- The review identifies knowledge gaps and proposes future research directions to enhance urolithin therapeutic potential.

## Abstract

Over the past decade, research on urolithins has expanded significantly due to their role as mediators between polyphenol-rich diets and human health. Understanding the relationships between ellagitannin intake, gut microbiota composition, and urolithin production is essential for evaluating their biological effects and nutraceutical potential. The primary objective of this review is to critically summarise current knowledge on urolithins, bioactive metabolites derived from ellagitannins in plant-based foods, with a focus on their biosynthesis, bioavailability, protein interactions, and potential therapeutic applications. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify studies on urolithin biosynthesis, absorption, transport mechanisms, protein binding, and incorporation into extracellular vesicles. Relevant articles were critically analysed to synthesise current evidence and highlight emerging concepts. Key findings indicate that after absorption, urolithins bind to serum albumin, which facilitates their transport to target tissues, exerting anti-inflammatory and antioxidant actions. Recent evidence also shows that urolithins can be packaged into extracellular vesicles, suggesting novel mechanisms for intracellular transport and potential therapeutic applications. This review highlights gaps in current knowledge and proposes directions for future research to optimise their therapeutic potential.