Exploring the effects of phenolic compounds to reduce intestinal damage and improve the intestinal barrier integrity: A systematic review of in vivo animal studies.

BACKGROUND & AIMS: The integrity of the intestinal barrier in the diseased is key to prevent further complications and disease such as sepsis and death, whereas, the role of food bioactive molecules (i. e. phenolic compounds (PCs) on the intestinal barrier, is still unknown. The current aim was to explore the benefits of the oral PC administration on the intestinal barrier integrity in animals. METHODS: The effects of PCs on the intestinal barrier integrity in in vivo animal models of intestinal inflammation were assessed up-to August 2020 from the PubMed, SCOPUS, and Cochrane Library databases under the PRISMA methodology. The risk of bias was assessed from ARRAY and SCYRCLE tools. RESULTS: From 1241 articles, 14 studies were included. In animals, oral resveratrol (n = 6) improves the intestinal barrier integrity and reduces intestinal damage. Additionally, grape seed extract (n = 2), curcumin (n = 1), genistein (n = 1), chlorogenic acid (n = 1), grape pomace (n = 1), olive leaf (n = 1) or cranberry extract (n = 1) improve the intestinal barrier integrity downregulating various inflammatory molecules (TNF-α, and other interleukins), and increasing the antioxidant enzymes in animals. Furthermore, resveratrol, quercetin, epigallocatechin, and other PCs improve the epithelial barrier integrity and pro-inflammatory molecule expression in the intestinal epithelia. CONCLUSIONS: The oral PC administration in animals improves the intestinal barrier integrity and function from three main mechanisms: 1) The reduction of pro-inflammatory molecules, 2) the improvement in tight-junction protein expression, and 3) the improvement of the antioxidant intracellular activity suggesting the potential use of PCs in the management of intestinal injury in humans, particularly for resveratrol, the most studied PC.

Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats.

Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone-quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were evaluated within the dose range tested. Following HT administration, dose-dependent effects were observed for the recovery of all the metabolites studied. At the lowest dose of 1 mg/kg, the glucuronidation pathway was the most relevant (25-30%), with lower recoveries for sulfation (14%), while at the highest dose of 100 mg/kg, sulfation was the most prevalent (75%). In addition, we report for the first time the formation of the mercapturate conjugate of HT in a dose-dependent manner. The biochemical data did not reveal significant toxic effects of HT at any of the doses studied. An increase in the GSH/GSSG ratio at the highest dose was observed indicating that the products of HT autoxidation are counteracted by glutathione, resulting in their detoxification. These results indicate that the metabolic disposition of HT is highly dependent on the dose ingested.

Biomarkers of food intake and metabolite differences between plasma and red blood cell matrices; a human metabolomic profile approach.

Untargeted metabolomic analyses of plasma and red blood cells (RBCs) can provide complementary information on biomarkers of food consumption. To assess blood collection differences in biomarkers, fasting blood was drawn from 10 healthy individuals using sodium citrate and lithium heparin as anticoagulants. Plasma and RBCs were separated into aqueous and lipid fractions to be analyzed using 1D and 2D (1)H NMR spectroscopy. Fatty acids were analyzed using gas chromatography-mass spectrometry (GC-MS). Polyphenols were extracted from plasma and RBCs by micro-elution solid-phase extraction and analyzed by ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). (1)H NMR demonstrated higher aqueous metabolites such as glucose in plasma compared to RBCs, while RBCs contained higher ADP-ATP, creatine and acetone than plasma. Lipoproteins and their subclasses were higher in plasma than in RBCs. Percentages of saturated fatty acids (SFA) 16 : 0, 17 : 0, 20 : 0, 24 : 0 and polyunsaturated fatty acids (PUFA) 22 : 6 n-3 (docosahexaenoic acid) and 20 : 4 n-6 (arachidonic acid) were higher in RBCs than in plasma (p < 0.05), while SFA 14 : 0, monounsaturated fatty acids (MUFA) 14 : 1 n-5, 16 : 1 n-7, 17 : 1 n-7 and 18 : 1 n-9 and PUFA 18 : 3 n-3, 18 : 2 n-6, 18 : 3 n-6 and 20 : 3 n-6 were higher in plasma than in RBCs (p < 0.05). Polyphenols differed in plasma from those of RBCs. Biomarker concentrations were lower in sodium citrate compared to lithium heparin plasma. In conclusion, metabolomic profiles generated by NMR spectroscopy, GC-MS and UPLC-MS/MS analyses of RBCs versus plasma show complementary information on several specific molecular biomarkers that could be applied in nutritional assessment.