Rositsa Mihaylova, Viktoria Elincheva, Georgi Momekov, Rumyana Simeonova
The present review offers a comprehensive synthesis of the structural diversity, natural occurrence, and therapeutic promise of key ellagitannins (punicalagin, sanguiin H-6, corilagin, geraniin, oenothein B, chebulagic, and chebulinic acids) within the hydrolyzable ellagitannin pool. Distributed in medicinal and dietary plants long used in traditional medicine, ellagitannin-rich species serve as sources of both complex polyphenolic scaffolds and their bioactive metabolites, urolithins, which mediate many of their health-promoting effects. Special emphasis is placed on the multifaceted mechanisms that contribute to their potent antioxidant, anti-inflammatory, antimicrobial, and anticancer effects, extending to both non-communicable and communicable diseases. Despite their broad therapeutic spectrum, clinical translation is limited by challenges such as poor bioavailability, host-gut microbiota variability, and a lack of robust in vivo evidence. The review highlights future directions aimed at unlocking ellagitannins' potential, including microbiota-targeted strategies for urolithin production, the design of stable prodrugs and analogs, and innovative delivery platforms. By integrating phytochemical, mechanistic and translational insights, this article positions ellagitannins as promising candidates for the development of novel polyphenol-based interventions.