Milica Kojadinović

Over the past decade, research on urolithins has expanded significantly due to their role as mediators between polyphenol-rich diets and human health. Understanding the relationships between ellagitannin intake, gut microbiota composition, and urolithin production is essential for evaluating their biological effects and nutraceutical potential. The primary objective of this review is to critically summarise current knowledge on urolithins, bioactive metabolites derived from ellagitannins in plant-based foods, with a focus on their biosynthesis, bioavailability, protein interactions, and potential therapeutic applications. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify studies on urolithin biosynthesis, absorption, transport mechanisms, protein binding, and incorporation into extracellular vesicles. Relevant articles were critically analysed to synthesise current evidence and highlight emerging concepts. Key findings indicate that after absorption, urolithins bind to serum albumin, which facilitates their transport to target tissues, exerting anti-inflammatory and antioxidant actions. Recent evidence also shows that urolithins can be packaged into extracellular vesicles, suggesting novel mechanisms for intracellular transport and potential therapeutic applications. This review highlights gaps in current knowledge and proposes directions for future research to optimise their therapeutic potential.

Secondary polyphenol metabolites, urolithins (UROs), have anti-oxidative, anti-inflammatory, and antidiabetic properties. Therefore, their biological activity relies on blood transport via human serum albumin (HSA) and tissue distribution. The main goal we set was to investigate the interaction between HSA and different URO (URO A, URO B, URO C, URO D, and glucuronidated URO A and B) using a combination of multi-spectroscopic instrumental and in silico approaches. The fluorescence spectroscopy revealed that URO can quench the naturally occurring fluorescence of HSA in a concentration-dependent manner. The HSA fluorescence was quenched by both a static and dynamic mechanism. The results showed that free UROs bind to HSA with higher affinity than their conjugated forms. CD spectroscopy and FTIR revealed that the alpha-helical structure of HSA is preserved. The calculated Gibbs free energy change indicates that the URO–HSA complex forms spontaneously. There is a single binding site on the HSA surface. The molecular docking results indicated that unconjugated Uro binds to Sudlow I, while their conjugation affects this binding site, so in the conjugated form, they bind to the cleft. Docking experiments indicate that all UROs are capable of binding to both thyroxine recognition sites of ligand-bound HSA proteins. Examining interactions under the following conditions (298 K, 303 K, and 310 K, pH 7.4) is of great importance for determining the pharmacokinetics of these bioactive compounds, as the obtained results can be used as a basis for modulating the potential dosing regimen.

The intake and status of micronutrients represent a significant research area aimed at preventing and treating the progression of renal impairment. Polyunsaturated fatty acids (PUFA), play a significant role in cardiovascular health and renal function. The study aimed to investigate the relationship between dietary magnesium, zinc, and vitamin B6 intake and the status of PUFAs in serum and erythrocyte phospholipids among CKD (chronic kidney disease) patients. Data on magnesium, zinc, and vitamin B6 intake were obtained through two 24-hour dietary recall questionnaires voluntarily completed by patients (one for a regular workday and one for a weekend day). PUFA profiles were determined using gas chromatography. Only 5.4% of patients had an adequate dietary intake of magnesium, 32.1% and 23.6% of patients had the recommended intake of zinc and vitamin B6, respectively. The sum of EPA+DHA content in plasma phospholipids of our patients was 2.61%, representing a very low level. The mean value for omega-3 index in erythrocytes was 4.3%, that is according to literature data related to the moderate risk for cardiovascular diseases in CKD patients. The study revealed the positive correlations between dietary magnesium and zinc intake with PUFAs (n-6 PUFA for magnesium and n-3 PUFA for zinc) and estimated D-6 desaturase activity (for magnesium) in serum phospholipids in CKD patients. The study provides novel findings about inadequate dietary intake of magnesium, zinc, vitamin B6, and n-3 PUFA in CKD patients. Moreover, it highlights the role of dietary magnesium intake in metabolism of PUFA in CKD patients, but further studies are necessary to establish a precise relationship between these micronutrients and PUFAs in a larger sample of patients.

Background: Recent literature data highlights metabolic changes in amyotrophic lateral sclerosis (ALS). To explore possible early metabolic changes, we aimed to analyse the fatty acids (FA) composition of erythrocytes in newly diagnosed als patients and to see whether fatty acid levels correlate with the ALSFRS-R score or disease duration. Methods: The severity of motor function involvement was assessed by the ALSFRS-R scale at the initial evaluation. The fatty acid profile of erythrocyte membranes was analysed by gas-liquid chromatography. The study comprised 26 clinically diagnosed als patients, with mean ALSFRS-R 38±8. The control group included 26 healthy volunteers. Results: Significantly higher levels of palmitic acid and total saturated FAs were detected in als patients. In als patients, total monounsaturated FA, palmitoleic, vaccenic, and oleic acid were also significantly increased. The levels of eicosapentaenoic acid, docosapentaenoic acid, total polyunsaturated FA (PUFA) and n-6 PUFA were significantly lower in als patients. Additionally, a-linolenic acid, the precursor of the n-3 PUFA family, was not detected in als patients. We found no significant correlation between the ALSFRS-R score and the abundance of individual FAs analysed. A moderate negative correlation was found between disease duration and DHA level, and a positive correlation was detected with MUFA. Conclusion: Experimental evidence presented may contribute to shaping a beneficial nutritional intervention.

Pomegranate juice (PJ) has potential positive effects in patients with metabolic disturbances due to a high content of polyphenols. The objective of this study was to evaluate effects of a 2-week consumption of dietary doses of PJ on blood pressure, lipid metabolism, and oxidative stress markers in overweight patients with dyslipidemia. Twenty-four patients, 8 males and 16 females, 40–60 years of age, with established overweight and dyslipidemia were randomly assigned into intervention group, who consumed 300 mL of PJ daily for 2 weeks, or control group. After 2 weeks of juice intake, intervention group had significantly lower diastolic blood pressure, low-density lipoprotein cholesterol, aminotransferase, and activity of glutathione peroxidase. Furthermore, patients who consumed PJ had reduced percentage of docosahexaenoic acid (22:6n-3, DHA) in plasma phospholipids and increased estimated activity of stearoyl-CoA desaturase. In erythrocytes, we found a significant increase in the levels of dihomo-γ- linolenic acid (20:3n-6, DGLA) and DHA, as well as in estimated activity of Δ6 desaturase, and a decrease in estimated activity of Δ5 desaturase. These results show that even a short-term consumption of dietary doses of PJ exerts beneficial effects and affects lipid metabolism in overweight patients with dyslipidemia.