A Hybrid In Silico/In Vitro Target Fishing Study to Mine Novel Targets of Urolithin A and B: A Step Towards a Better Comprehension of Their Estrogenicity.

SCOPE: Urolithin A and B are gut metabolites of ellagic acid and ellagitannins associated with many beneficial effects. Evidence in vitro pointed to their potential as estrogenic modulators. However, both molecular mechanisms and biological targets involved in such activity are still poorly characterized, preventing a comprehensive understanding of their bioactivity in living organisms. This study aimed at rationally identifying novel biological targets underlying the estrogenic-modulatory activity of urolithins. METHODS AND RESULTS: The work relies on an in silico/in vitro target fishing study coupling molecular modeling with biochemical and cell-based assays. Estrogen sulfotransferase and 17ß-hydroxysteroid dehydrogenase are identified as potentially subject to inhibition by the investigated urolithins. The inhibition of the latter undergoes experimental confirmation either in a cell-free or cell-based assay, validating computational outcomes. CONCLUSIONS: The work describes target fishing as an effective tool to identify unexpected targets of food bioactives detailing the interaction at a molecular level. Specifically, it described, for the first time, 17ß-hydroxysteroid dehydrogenase as a target of urolithins and highlighted the need of further investigations to widen the understanding of urolithins as estrogen modulators in living organisms.

Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

BACKGROUND: A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. METHODS: Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. RESULTS: We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). CONCLUSIONS: The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.

Wheat aleurone polyphenols increase plasma eicosapentaenoic acid in rats.

METHODS: These studies were designed to assess whether wheat polyphenols (mainly ferulic acid [FA]) increased the very-long-chain omega-3 fatty acids (VLC n-3) [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in rats. Wheat aleurone (WA) was used as a dietary source of wheat polyphenols. Two experiments were performed; in the first one, the rats were fed WA or control pellets (CP) in presence of linseed oil (LO) to provide alpha-linolenic acid (ALA), the precursor of VLC n-3. In the second one, the rats were fed WA or CP in presence of control oil (CO) without ALA. The concentrations of phenolic acid metabolites in urine were also investigated. RESULTS: The urinary concentration of conjugated FA increased with WA ingestion (p<0.05). Plasma EPA increased by 25% (p<0.05) with WA in the CO group but not in the LO group. In contrast, there was no effect of WA on plasma DHA and omega-6 fatty acids (n-6). Finally, both n-3 and n-6 in the liver remained unchanged by the WA. CONCLUSION: These results suggest that WA consumption has a significant effect on EPA in plasma without affecting n-6. Subsequent studies are required to examine whether these effects may explain partly the health benefits associated with whole wheat consumption.

Effects of different maturity stages on antioxidant content of Ivorian Gnagnan (Solanum indicum L.) berries.

Gnagnan (Solanum indicum L.) is a spontaneous plant widely distributed in Ivory Coast. During ripening stages, Solanum indicum L. presents different colours (green, yellow and red) and is reported to contain several albeit poorly characterized antioxidant compounds. This paper describes in detail the antioxidant profile (ascorbic acid, carotenoids and polyphenols), antioxidant capacity (FRAP test and Folin-Ciocalteau assay) and the colour changes of Gnagnan berries at different ripening levels. Ascorbic acid content was similar in green and yellow berries, but significantly lower in red ones. Red berries showed a higher content of carotenoids compared to green and yellow ones. Regarding polyphenols, several phenolic acids and flavonoids were found in all berries. The content of caffeoylquinic acids, caffeic acid, flavonol glycosides and naringenin was higher in red berries, while the content of p-coumaric acid and feruloylquinic acids was similar among the three colours. The FRAP assay increased with the ripening process, whereas total polyphenols were similar among berries. Significant differences were found for the colorimetric indexes among products of different degrees of ripening. The present results show the important role of the ripening stage in increasing the antioxidant content of Gnagnan berries.