Urolithins: The Colon Microbiota Metabolites as Endocrine Modulators: Prospects and Perspectives

Abstract

Selective estrogen receptor modulators (SERMs) have been used in hormone related disorders, and their role in clinical medicine is evolving. Tamoxifen and raloxifen are the most commonly used synthetic SERMs, and their long-term use are known to create side effects. Hence, efforts have been directed to identify molecules which could retain the beneficial effects of estrogen, at the same time produce minimal side effects. Urolithins, the products of colon microbiota from ellagitannin rich foodstuff, have immense health benefits and have been demonstrated to bind to estrogen receptors. This class of compounds holds promise as therapeutic and nutritional supplement in cardiovascular disorders, osteoporosis, muscle health, neurological disorders, and cancers of breast, endometrium, and prostate, or, in essence, most of the hormone/endocrine-dependent diseases. One of our findings from the past decade of research on SERMs and estrogen modulators, showed that pomegranate, one of the indirect but major sources of urolithins, can act as SERM. The prospect of urolithins to act as agonist, antagonist, or SERM will depend on its structure; the estrogen receptor conformational change, availability and abundance of co-activators/co-repressors in the target tissues, and also the presence of other estrogen receptor ligands. Given that, urolithins need to be carefully studied for its SERM activity considering the pleotropic action of estrogen receptors and its numerous roles in physiological systems. In this review, we unveil the possibility of urolithins as a potent SERM, which we are currently investigating, in the hormone dependent tissues.

Medicinal Plants and Their Impact on the Gut Microbiome in Mental Health: A Systematic Review

“…Meanwhile, it is well known that ellagitannins are decomposed to ellagic acid and further to urolithins by gut microbiota, with different metabotypes that are capable of producing differing urolithin patterns [ 239 ]. Urolithins have been predicted in silico to pass the BBB [ 240 ], and they have shown the potential to exert neuroprotective effects mainly in cellular models, but their possible beneficial effects related to mental health still need to be studied systematically [ 241 ].…”

Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose

“…So far, various conditions (e.g., concentration, incubation time, conjugates, or free aglycones) for in vitro studies on urolithins have been used by different authors. It still remains questionable, however, to what extent the experiments yield physiologically relevant results [ 16 ]. Nevertheless, it is tempting to consider future treatment of podocytes (e.g., with nanoparticle carriers that would transport active urolithin aglycones directly to the target cells).…”

“…In humans, metabotype A is predominant [ 14 ]. The diverse biological properties of urolithins include antioxidant, anti-inflammatory, anti-cancer, neuroprotective, antiglycative and other activities [ 15 , 16 ] that are exerted by the modulation of signaling molecules, cell structure, and protein expression [ 17 ]. Moreover, following human trials [ 18 ], urolithins are considered safe, and UA has been recently approved by the US Food and Drug Administration (FDA) as generally recognized as safe (GRAS) for its use as an ingredient.…”

Recent Advances and Perspectives on the Health Benefits of Urolithin B, A Bioactive Natural Product Derived From Ellagitannins

“…Finally, the drug sensitivity of phase II metabolites of Uro on cancer cells has not been fully explained at a molecular level ( Tang et al, 2021 ; Vini et al, 2021 ). In addition, more animal studies with Uro B combined with other anticancer drugs should be conducted.…”