The Therapeutic Relevance of Urolithins, Intestinal Metabolites of Ellagitannin-Rich Food: A Systematic Review of In Vivo Studies

Abstract

The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a growing trend in urolithin research pertaining to its pharmacological properties. The purpose of this systematic review is to collate and synthesise all available data on urolithin’s therapeutic ability, to highlight its potential as a pharmaceutical agent, and prospective direction on future research. Methods: This systematic review was written based on the PRISMA guideline and was conducted across Ovid via Embase, Ovid MEDLINE, Cochrane Central Register for Controlled Trials, and Web of Science Core Collection. Results: A total of 41 animal studies were included in this systematic review based on the appropriate keyword. The included studies highlighted the neuroprotective, anti-metabolic disorder activity, nephroprotective, myocardial protective, anti-inflammatory, and musculoskeletal protection of urolithin A, B, and its synthetic analogue methylated urolithin A. The Sirt1, AMPK, and PI3K/AKT/mTOR signalling pathways were reported to be involved in the initiation of autophagy and mitochondrial biogenesis by urolithin A. Conclusions: This review methodically discusses the therapeutic prospects of urolithins and provides scientific justification for the potential development of urolithin A as a potent natural mitophagy inducer for anti-ageing purposes.

Urolithin A improves Alzheimer’s disease cognition and restores mitophagy and lysosomal functions

“…UA at dose from 250 mg to 2000 mg in humans [26] and 1-450 mg/kg in mice [79] has been reported to be safe. UA increased muscle strength and physical performance in a 6 min walk test in elderly humans after four months of supplementation [80].…”

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

“…Urolithins include several penta-, tetra-, tri-, di-, and monohydroxylated compounds dependent on the level of hydroxylation on the ellagitannins from the diet promoted by gut bacteria, mainly Gordonibacter urolithinfaciens and Gordobacter pamelaceae, on the ellagitannins from the diet [149]. Other gut bacteria that can participate in the production of urolithins are the Ellagibacteris isourilithinifaciens and strains of Bifidobacteria, mainly Bifidobacterium pseudocatenulatum [150]. The main dietary sources of ellagitannins include pomegranate (Punica granatum L., Lythraceae botanical family) fruits, several nuts, mainly walnuts (Juglans regia L., Junglandaceae botanical family), and several species of raspberries, mainly red raspberries (Rubus idaeus L., Rosaceae family) and black raspberries (Rubus occidentalis L.), and black tea (Camelia sinensis (L.) Kuntze, Theaceae botanical family).…”

Urolithin A Ameliorates Athletic Ability and Intestinal Microbiota in Sleep Deprivation from the Perspective of the Gut‐Muscle Axis

“…[ 8 ] It exhibits a wide range of beneficial bioactive properties including anti‐ageing, anti‐metabolic disorder, and immunomodulatory activities. [ 9 ] In the human stomach and small intestine, the absorbed ellagic tannins are hydrolyzed into ellagic acid, and then converted into urolithins with high bioavailability by the intestinal microbiota. [ 10 ] UA could modulate favorably the gut microbiota [ 11 ] and maintain gut barrier integrity through inflammation‐related signaling pathways.…”