Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

Abstract

Oxidative stress is a state of excess of prooxidative species relative to the antioxidant defenses (enzymatic and nonenzymatic) in a living organism. The consequence of this imbalance is damage of the major cellular macromolecules (carbohydrates, lipids, proteins, and DNA), which further leads to a gradual loss of tissue and organ function. It has been shown that oxidative stress plays an important role in the pathogenesis of many chronic diseases (cardiovascular, metabolic, and neurodegenerative diseases and cancer) and in the process of aging. Thus, many strategies to combat oxidative stress have been proposed and tested. In this context, food rich in antioxidants has received great attention. Pomegranate, berries, and walnuts have been recognized as “superfood” particularly for their cardioprotective effects. The common characteristic of these foods is the high content of ellagitannins. Since tannins are not bioavailable, they have been neglected in nutrition science and even considered antinutrients for a long time. However, this view has changed dramatically once it was recognized that ellagic acid, released from ellagitannins in the gastrointestinal system, is further metabolized by colonic microbiota to bioavailable compounds—known as urolithins. Thus, urolithins (3,4-benzocoumarin derivatives) have emerged as novel natural bioactive compounds and are now the focus of extensive investigations. So far, urolithins were shown to be powerful modulators of oxidative stress and agents with potential anti-inflammatory, antiproliferative, and antiaging properties. Furthermore, a few synthetic derivatives of urolithins were recognized as lead compounds for new drug development. Available data on urolithin synthesis, physicochemical and pharmacokinetic characteristics, biological activity, and safety will be presented in this review.

Antitussive, Antioxidant, and Anti-Inflammatory Effects of a Walnut (Juglans regia L.) Septum Extract Rich in Bioactive Compounds

“…Other biomolecules found in WS that can be involved in the antioxidant and anti-inflammatory activities are the ellagitannins. In the gastrointestinal tract, ellagic acid, released from ellagitannins, is metabolized by the colonic microorganisms to urolithins, important modulators of oxidative stress and inflammatory action [ 46 ].…”

Physiological and Immune Functions of Punicalagin

“…As a result of this imbalance, important cellular macromolecules (lipids, carbohydrates, proteins and DNA) are damaged. Oxidative stress is also associated with the manifestation of many chronic diseases, such as metabolic, neurodegenerative, cardiovascular, lung, kidney and cancer diseases [ 53 , 54 ]. Several antioxidants have been described that have a beneficial effect against oxidative stress, including PUN, and metabolized EA and urolithins.…”

Pectin-Based Formulations for Controlled Release of an Ellagic Acid Salt with High Solubility Profile in Physiological Media

“…In addition, even upon high free EA intake, EA concentration in plasma was always quite low [ 11 ]. It has been demonstrated that in the grand intestine tract, EA undergoes an extensive metabolism by the gut microbiota providing urolithins, which are 25–80-fold more bioavailable and much better absorbed than EA [ 12 , 13 ]. Based on these data, interest has significantly increased in recent years for the development of delivery systems that might increase the solubility in water and bioavailability of EA, preserve its structural integrity, and warrant its controlled release at the physiological target [ 14 ].…”