Ellagitannins (ETs)

Ellagitannins are a complex and diverse class of hydrolyzable tannins characterized by a glucose core esterified with hexahydroxydiphenic acid (HHDP) units. They are potent dietary polyphenols found in high concentrations in pomegranates, berries, and walnuts [4, 7]. Upon ingestion, these compounds are not typically absorbed intact but are hydrolyzed to ellagic acid and subsequently metabolized by the gut microbiota into bioactive molecules known as urolithins [11, 12]. These metabolites circulate systemically and exert antioxidant, anti-inflammatory, and anti-proliferative effects by modulating signaling pathways such as NF-κB, MAPK, and Nrf2 [1, 21]. While ellagitannins are widely investigated for their therapeutic potential in treating cancer, metabolic syndrome, and cardiovascular diseases, they are considered dietary bioactive compounds or drug leads rather than biological targets like receptors or enzymes [5, 13]. Their clinical application is primarily challenged by low oral bioavailability and significant inter-individual variability in gut microbiota composition, which determines a person's "metabotype" and their ability to produce therapeutic urolithins [12, 14]. Consequently, most research focuses on their role as pleiotropic agents that hit multiple intracellular targets rather than a single specific receptor [20].

Other names

Hydrolyzable tanninsPunicalaginsSanguiinsGeraniinsHexahydroxydiphenic acid estersCorilagins

Ellagitannins function primarily via their gut microbiota-derived metabolites, urolithins, which inhibit NF-κB and MAPK inflammatory signaling, activate Nrf2-mediated antioxidant defenses, and promote SIRT1/AMPK-dependent mitophagy.