Polyphenol-rich Foods Research Articles

İnsülin Direncine Etki Eden Besinler

İnsülin direnci, başta diyabet ve metabolik sendrom olmak üzere birçok hastalığın oluşum sürecinde rol oynayabilen önemli bir aktördür. Fiziksel aktivite ve beslenme gibi değiştirilebilir yaşam koşulları ile insülin direnci oluşumunun önüne geçilebilmektedir. Bu derleme yazının amacı, insülin direnci oluşumu ve yönetimi sürecinde etkili olduğu düşünülen besinleri incelemek ve olası yararları üzerinde durmaktır. Bu bağlamda, derleme kapsamında polifenol içeriği yüksek besinler ile posadan zengin besinler değerlendirilmiştir. İnsülin direncine etki eden ve etki ettiği düşünülen pek çok besin olmasına karşılık, tartışmalı ve zıt çalışmalar mevcuttur. Bu nedenle tek bir besin üzerinde yoğunlaşmak yerine diyetteki besin çeşitliliğini arttırıp, sözü geçen besinlerin diyete uygun miktarlarda eklenmesi daha yararlı bir yaklaşım olacaktır.

Olive oil industry by-products. Effects of a polyphenol-rich extract on the metabolome and response to inflammation in cultured intestinal cell

Over the past years, researchers and food manufacturers have become increasingly interested in olive polyphenols due to the recognition of their biological properties and probable role in the prevention of various diseases such as inflammatory bowel disease. Olive pomace, one of the main by-products of olive oil production, is a potential low-cost, phenol-rich ingredient for the formulation of functional food. In this study, the aqueous extract of olive pomace was characterized and used to supplement human intestinal cell in culture (Caco-2). The effect on the cell metabolome and the anti-inflammatory potential were then evaluated. Modification in the metabolome induced by supplementation clearly evidenced a metabolic shift toward a “glucose saving/accumulation” strategy that could have a role in maintaining anorexigenic hormone secretion and could explain the reported appetite-suppressing effect of the administration of polyphenol-rich food. In both basal and inflamed condition, supplementation significantly reduced the secretion of the main pro-inflammatory cytokine, IL-8. Thus, our data confirm the therapeutic potential of polyphenols, and specifically of olive pomace in intestinal bowel diseases. Although intervention studies are needed to confirm the clinical significance of our findings, the herein reported results pave the road for exploitation of olive pomace in the formulation of new, value-added foods. In addition, the application of a foodomics approach allowed observing a not hypothesized modulation of glucose metabolism.

Grape Pomace: Antioxidant Activity, Potential Effect Against Hypertension and Metabolites Characterization after Intake.

Observational studies indicate that the intake of polyphenol-rich foods improves vascular health, thereby significantly reducing the risk of hypertension and cardiovascular disease (CVD). Therefore, the aim of this study was to analyse the remained potential of grape by-products from important Rhône Valley red wine cultivars: Grenache, Syrah, Carignan, Mourvèdre and Alicante. For that, six different extracts from grape pomaces, selected by their antioxidant activity, were studied in vivo during six weeks with spontaneously hypertensive rats (SHR). Extracts used in SHR1, SHR2 and SHR6 groups presented a « rebound effect » on systolic blood pressure, whereas the other extracts do not change it significantly. The bioavailability of Grenache (GRE1) (EA70) seed pomace extract (SHR1 group), Mouvendre (MOU) (EA70) skin pomace extract (SHR5 group) and Alicante (ALI) (EA70) skin pomace extract (SHR6 group) was studied by High Performance Liquid Chromatography with Photodiode Array detector and Electrospray Ionization Mass Spectrometer (HPLC-PDA-ESI-MSn) in urine, plasma and tissues to search differences on the metabolism of the different extracts intake.

Polyphenol-rich foods and risk of gestational diabetes: a systematic review and meta-analysis.

Animal studies have demonstrated anti-diabetic properties of several food-derived polyphenols, but data in humans remains unclear. This study aimed to review and meta-analyse evidence concerning the effect of the intake of several polyphenol-rich foods on gestational diabetes (GDM) risk. A systematic literature search was conducted in PubMed, Web of Science and Embase databases for observational studies on the association between dietary intake of foods/diets rich in polyphenols and GDM risk. Inclusion criteria were original research articles with full texts published in peer-reviewed English language journals, which investigated foods within the top 100 richest dietary sources of polyphenols and reported odds ratio/relative risk with their corresponding 95% confidence intervals. The quality of included studies was assessed using the Newcastle-Ottawa Scale. The intake of polyphenol-rich foods and dietary patterns in relation to GDM were pooled with fixed- and random-effects models. In total, 12 (10 cohort, 1 cross-sectional and 1 case-control) studies were included for the final systematic review, comprising 124,959 participants and including 5,786 women with GDM. Five studies found a significant, inverse association between the intake of polyphenol-rich foods or Mediterranean diet and GDM, whereas five studies reported no association and two exhibited a positive association. Meta-analyses further showed that the risk of GDM was about halved amongst women with the highest score of Mediterranean diet compared to those with the lowest score. The results suggest that dietary patterns rich in polyphenols may reduce the risk of GDM despite inconclusive evidence for polyphenol-rich food groups.

Ellagitannins from Pomegranate Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis in Rats while Enhancing Its Chemotoxicity against HT-29 Colorectal Cancer Cells through Intrinsic Apoptosis Induction

Worldwide, colorectal cancer (CRC) is a deleterious disease causing millions of death annually. 5-Fluorouracil (5-FU) is a first-line chemotherapy for CRC, but chemoresistance and gastrointestinal mucositis limit its efficacy. Polyphenol-rich foods are increasingly popular due to their potential beneficial roles in preventing and treating cancer. Ellagitannins are a group of phenolic compounds commonly found in pomegranate, strawberries, raspberries, etc. The objective of this study was to explore whether ellagitannins from pomegranate (PETs) could ameliorate 5-FU-induced intestinal mucositis and enhance the drug's efficacy against CRC. The results showed that PETs (100 mg/kg) counteracted 5-FU-induced intestinal mucositis in rats. The number of apoptotic cells per crypt was reduced from 1.50 ± 0.21 to 0.85 ± 0.18 ( P < 0.05). Moreover, PETs induced HT-29 CRC cell death through intrinsic apoptosis, as demonstrated by dissipation of mitochondrial membrane potential, increased Bax-to-Bcl-2 ratio, and cleavage of caspase 9 and caspase 3. PETs and 5-FU combination treatments exhibited synergistic cytotoxicity against HT-29 cells with a weighted combination index of 0.3494. PETs (80 μg/mL) and 5-FU (40 μg/mL) treatments for 48 h induced 14.03 ± 0.76% and 16.42 ± 1.15% of HT-29 cells to undergo apoptosis, while the combination treatment further increased apoptosis of cells to 34.00 ± 1.54% ( P < 0.05). Combination treatment of the cells also enhanced S phase cell cycle arrest as compared with PETs or 5-FU monotherapy ( P < 0.05). These results suggest that dietary ellagitannins from pomegranate could alleviate intestinal mucositis in rats induced by 5-FU while enhancing its toxicity against HT-29 cells through potentiation of apoptosis and cell cycle arrest.

Polyphenols and Microvascular Function in Humans: A Systematic Review.

Polyphenol-rich dietary sources are acknowledged to have potential cardiovascular health benefits, particularly in reducing cardiovascular disease risk. This systematic review sought to determine the effect of polyphenol-rich foods and beverages upon microvascular function, which is of considerable importance in its contribution towards the pathophysiology of microvascular-related complications but also in the future development of (macro-vessel) cardiovascular disease. Overall, consumption of polyphenol-rich foods and beverages demonstrate improved microvascular function, although this is dependent upon the polyphenol source, the dose of the product, the duration of consumption and the population group studied. Most subgroups reviewed suggest an overall beneficial effect on microvascular function, particularly grape-derived products, cocoa, tea, pine bark and Rutaceae aurantiae. Other groups remain equivocal and require further study due to the limited research performed to date. Polyphenols are abundant in the human diet and this systematic review demonstrates that they are an inexpensive, non-pharmacological approach for improving cardiovascular health in currently healthy individuals and in populations with microvascular dysfunction.

Polyphenols, Antioxidants and the Sympathetic Nervous System.

A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity, metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympathoexcitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic strategy to reduce the deleterious effects of increased adrenergic tone, particularly in essential hypertension.

Making Milk Less Allergenic

The formation of stable aggregates by food proteins is associated with allergenicity. In particular, amyloid formation by the fish allergen parvalbumin was recently shown to favor IgE binding and subsequent allergic recognition. Therefore, reducing amyloid content in an allergenic food might offer a direct way to make that food less likely to trigger an allergy. In this project, protein aggregation and amyloid formation were studied in milk using gel electrophoresis and fluorescence-based assays. The results suggested that ordinary pasteurized milk from the grocery store contained protein aggregates and specifically amyloid. Processing the milk as normally done during food preparation did not appreciably affect general aggregation or amyloid formation. However, the addition of some polyphenol-containing food products to the milk appeared to result in reduced amyloid levels. Moreover, cranberry juice also appeared to reduce amyloid formation by the milk protein casein. These results suggest that the addition of cranberry or other polyphenol-rich foods to milk products for young children may reduce the risk of milk allergy development by diminishing protein aggregation.

Efficacy of Nutritional Interventions on Inflammatory Markers in Haemodialysis Patients: A Systematic Review and Limited Meta-Analysis.

Low-grade chronic inflammation is prevalent in patients undergoing haemodialysis (HD) treatment and is linked to the development of premature atherosclerosis and mortality. The non-pharmacological approach to treat inflammation in HD patients through nutritional intervention is well cited. We aimed to assess the efficacy of different nutritional interventions at improving inflammatory outcomes in HD patients, based on markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). We searched PubMed, Cochrane Library, and Embase for randomized controlled trials (RCT) published before June 2017. Inclusion criteria included RCTs on adult patients on maintenance HD treatment with duration of nutritional interventions for a minimum 4 weeks. Risk of bias was assessed using the Jadad score. In total, 46 RCTs experimenting different nutritional interventions were included in the review and categorized into polyphenols rich foods, omega-3 fatty acids, antioxidants, vitamin D, fibres, and probiotics. Meta-analyses indicated significant reduction in CRP levels by omega-3 fatty acids (Random model effect: −0.667 mg/L, p < 0.001) and vitamin E (fixed model effect: −0.257 mg/L, p = 0.005). Evidence for other groups of nutritional interventions was inconclusive. In conclusion, our meta-analysis provided evidence that omega-3 fatty acids and vitamin E could improve inflammatory outcomes in HD patients.

Protection by different classes of dietary polyphenols against palmitic acid-induced steatosis, nitro-oxidative stress and endoplasmic reticulum stress in HepG2 hepatocytes

Polyphenol-rich functional foods have shown promise in ameliorating NAFLD but the relative effectiveness and mechanisms of different polyphenols are largely unknown. In a model of steatosis using HepG2 hepatocytes exposed to palmitic acid, we investigated the effect of selected polyphenols (resveratrol, quercetin, catechin, cyanidin, kuromanin) and berberine. Exposure to palmitic acid produced steatosis and intracellular ROS production, which were prevented by all of the polyphenols and berberine, at 10 µM. Palmitic acid produced a 245% increase in mRNA for inducible nitric oxide synthase (iNOS) that was almost completely prevented by all of the polyphenols (but not by berberine). Most of the polyphenols also partially inhibited palmitic acid-induced increases in markers of endoplasmic reticulum stress, and decreases in mitochondrial content and mitochondrial membrane potential. In conclusion, the polyphenols all similarly prevented steatosis, ROS generation and iNOS induction, and protected against ER stress and mitochondrial impairment.

A computationally driven analysis of the polyphenol-protein interactome

Polyphenol-rich foods are part of many nutritional interventions aimed at improving health and preventing cardiometabolic diseases (CMDs). Polyphenols have oxidative, inflammatory, and/or metabolic effects. Research into the chemistry and biology of polyphenol bioactives is prolific but knowledge of their molecular interactions with proteins is limited. We mined public data to (i) identify proteins that interact with or metabolize polyphenols, (ii) mapped these proteins to pathways and networks, and (iii) annotated functions enriched within the resulting polyphenol-protein interactome. A total of 1,395 polyphenols and their metabolites were retrieved (using Phenol-Explorer and Dictionary of Natural Products) of which 369 polyphenols interacted with 5,699 unique proteins in 11,987 interactions as annotated in STITCH, Pathway Commons, and BindingDB. Pathway enrichment analysis using the KEGG repository identified a broad coverage of significant pathways of low specificity to particular polyphenol (sub)classes. When compared to drugs or micronutrients, polyphenols have pleiotropic effects across many biological processes related to metabolism and CMDs. These systems-wide effects were also found in the protein interactome of the polyphenol-rich citrus fruits, used as a case study. In sum, these findings provide a knowledgebase for identifying polyphenol classes (and polyphenol-rich foods) that individually or in combination influence metabolism.

Phytochemical and Pharmacological Properties of Capparis spinosa as a Medicinal Plant.

Over the past decades, there has been increasing attention on polyphenol-rich foods including fruits and vegetables on human health. Polyphenols have been shown to possess some potential beneficial effects on human health and they are widely found in foods consumed by populations worldwide. Capparis spinosa (C. spinosa) is an important source of different secondary metabolites of interest to humankind. The traditional therapeutic applications of C. spinosa have been reported in Ancient Romans. Numerous bioactive phytochemical constituents have been isolated and identified from different parts (aerial parts, roots and seeds) of C. spinosa which are responsible alone or in combination for its various pharmacological activities. Therefore, this paper is a review of publications on the phytochemical and pharmacological properties of C. spinosa. There is insufficient evidence to suggest that C. spinosa or its extracts are able to improve the biomarkers of cardiovascular disease and diabetes. However, these studies used different parts of C. spinosa plant, methods of preparation and types of solvents, which cause the evaluation of activity of C. spinosa difficult and involve quite heterogeneous data. There is also evidence, although limited, to suggest benefits of C. spinosa in improving human health. Therefore, the relationship between C. spinosa and improved human health outcomes requires further study.

Biochemical and molecular perspectives on polyphenol rich food, probiotic food, and their combination

Biochemical and molecular perspectives on polyphenol rich food, probiotic food, and their combination

Effect of novel technologies on polyphenols during food processing

Abstract Lifestyles have changed the eating norm of people leading to chronic and degenerative maladies. In fact, prevailing use of highly processed and convenient-to-eat foods have reduced intake of polyphenol rich food importantly fruits and vegetables. Polyphenols are important component of our diet with good antioxidant and high anti-inflammatory properties. Therefore, industries have started to implement particular food processing techniques crucial to achieve food products having high amount of health promoted components with appropriate shelf life. Nowadays, emerging technologies such as high hydrostatic pressure, pulsed electric field, ultrasound, microwave, ohmic heating and irradiation are being studied as an alternative to conventional ones, obtaining promising results. Energy efficiency, environment conservation, processing time reduction and retention of nutritional properties are key benefits for using innovative food processing technologies. The present review will summarize the current knowledge about different novel food processing technologies on the retention of polyphenols.

Biological Mechanisms by Which Antiproliferative Actions of Resveratrol Are Minimized.

Preclinical and clinical studies have offered evidence for protective effects of various polyphenol-rich foods against cardiovascular diseases, neurodegenerative diseases, and cancers. Resveratrol is among the most widely studied polyphenols. However, the preventive and treatment effectiveness of resveratrol in cancer remain controversial because of certain limitations in existing studies. For example, studies of the activity of resveratrol against cancer cell lines in vitro have often been conducted at concentrations in the low μM to mM range, whereas dietary resveratrol or resveratrol-containing wine rarely achieve nM concentrations in the clinic. While the mechanisms underlying the failure of resveratrol to inhibit cancer growth in the intact organism are not fully understood, the interference by thyroid hormones with the anticancer activity of resveratrol have been well documented in both in vitro and xenograft studies. Thus, endogenous thyroid hormones may explain the failure of anticancer actions of resveratrol in intact animals, or in the clinic. In this review, mechanisms involved in resveratrol-induced antiproliferation and effects of thyroid hormones on these mechanisms are discussed.

Cocoa, Blood Pressure, and Vascular Function.

Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.

O35 An anthocyanin-rich blackcurrant extract induced NO-mediated relaxation in coronary artery rings and eNOS phosphorylation in cultured endothelial cells: Role of sodium-glucose cotransporters 1 and 2

Introduction The beneficial cardiovascular effect of polyphenol-rich food and beverages has been attributed, at least in part, to an improved vascular function through an increased endothelial formation of nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH), two major vasoprotective mechanisms. Black currant is a rich source of anthocyanins, and, in particular, of glucoside- and rutinoside-conjugated delphinidin and cyanidin. This study evaluated the role of sodium-glucose cotransporters (SGLT) 1 and 2 in the blackcurrant extract (BCE)-induced NO-mediated endothelium-dependent relaxation and activation of endothelial NO synthase (eNOS). Methods The reactivity of porcine coronary artery rings was assessed in organ chambers, and the expression and phosphorylation level of proteins in cultured porcine coronary artery endothelial cells by Western blot analysis. Results BCE (310.0 ± 0.1 mg gallic acid equivalent/g) was prepared from a blackcurrant juice containing 2.7 g gallic acid equivalent/L of polyphenols using a Sephadex LH-20 column. BCE caused potent concentration-dependent relaxations of coronary artery rings with endothelium, which were significantly reduced by the dual SGLT1 and SGLT2 inhibitor LX4211, and also to some extent by the SGLT2 inhibitor canagliflozin but not dapagliflozin. In contrast, LX4211 did not affect relaxations to bradykinin, sodium nitroprusside and epigallocatechin gallate. BCE induced the phosphorylation of eNOS at the activator site Ser1177 in cultured endothelial cells, which was significantly prevented by LX4211, dapagliflozin and canagliflozin. Conclusion These observations indicate that BCE is a potent activator of eNOS and inducer of NO-mediated vasorelaxation possibly subsequent to the entry of conjugated anthocyanins via SGLT1/2 into endothelial cells.

Apple and blackcurrant polyphenol-rich drinks decrease postprandial glucose, insulin and incretin response to a high-carbohydrate meal in healthy men and women

Postprandial glycemic responses to meals are inhibited by polyphenol-rich plant foods. Combinations of polyphenols may be particularly effective through complementary mechanisms. A randomized, controlled, double-blinded cross-over trial was conducted in healthy volunteers to test the hypothesis that apple and blackcurrant polyphenol-rich drinks would reduce postprandial blood glucose concentrations. Secondary outcomes included insulin and glucose-dependent insulinotropic polypeptide (GIP) secretion. Twenty men (mean age 26 y, SD 8) and 5 postmenopausal women (mean age 57 y, SD 3) consumed a placebo drink (CON) and 2 polyphenol-rich drinks containing fruit extracts: either 1200 mg apple polyphenols (AE), or 600 mg apple polyphenols+600 mg blackcurrant anthocyanins (AE+BE), in random order with a starch and sucrose meal. Incremental areas under the curve (iAUC) for plasma glucose concentrations were lower following AE+BE over 0–30 and 0–120 min compared with CON; mean differences (95% CI) −32 mmol/L·min (−41, −22, P<.0005) and −52 mmol/L min (−94, −9, P<.05), respectively. AE significantly reduced iAUC 0–30 min (mean difference −26 mmol/L min, −35, −18, P<.0005) compared with CON, but the difference over 120 min was not significant. Postprandial insulin, C-peptide and GIP concentrations were significantly reduced relative to CON. A dose response inhibition of glucose transport was demonstrated in Caco-2 cells, including total and GLUT-mediated transport, and SGLT1-mediated glucose transport was strongly inhibited at all doses in Xenopus oocytes, following 10 min incubation with 0.125–4 mg apple polyphenols/ml. In conclusion, ingestion of apple and blackcurrant polyphenols decreased postprandial glycemia, which may be partly related to inhibition of intestinal glucose transport.

Identification of Urinary Polyphenol Metabolite Patterns Associated with Polyphenol-Rich Food Intake in Adults from Four European Countries.

We identified urinary polyphenol metabolite patterns by a novel algorithm that combines dimension reduction and variable selection methods to explain polyphenol-rich food intake, and compared their respective performance with that of single biomarkers in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 475 adults from four European countries (Germany, France, Italy, and Greece). Dietary intakes were assessed with 24-h dietary recalls (24-HDR) and dietary questionnaires (DQ). Thirty-four polyphenols were measured by ultra-performance liquid chromatography–electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS-MS) in 24-h urine. Reduced rank regression-based variable importance in projection (RRR-VIP) and least absolute shrinkage and selection operator (LASSO) methods were used to select polyphenol metabolites. Reduced rank regression (RRR) was then used to identify patterns in these metabolites, maximizing the explained variability in intake of pre-selected polyphenol-rich foods. The performance of RRR models was evaluated using internal cross-validation to control for over-optimistic findings from over-fitting. High performance was observed for explaining recent intake (24-HDR) of red wine (r = 0.65; AUC = 89.1%), coffee (r = 0.51; AUC = 89.1%), and olives (r = 0.35; AUC = 82.2%). These metabolite patterns performed better or equally well compared to single polyphenol biomarkers. Neither metabolite patterns nor single biomarkers performed well in explaining habitual intake (as reported in the DQ) of polyphenol-rich foods. This proposed strategy of biomarker pattern identification has the potential of expanding the currently still limited list of available dietary intake biomarkers.

20 The polyphenol delphinidin induces antioxidant effects in human umbilical vein endothelial cells through activation of endogenous glutathione: importance of using relevant concentration in in vitro systems

Polyphenols are regarded to have a wide range of health-promoting effects. Increased consumption of polyphenol-rich food is known to be associated with numerous cardioprotective effects. Polyphenols have been shown to improve endothelial function, inhibit abnormal platelet aggregation, reduce inflammation and improve plasma lipid profiles. Moreover, polyphenols have been widely recognised as powerful antioxidants. Given that oxidative stress plays a key role in initiation and progression of atherosclerosis, antioxidant therapy with polyphenols has potential. However, the concentrations required to mediate sufficient antioxidant effect appear to be unattainable under in vivo conditions. Polyphenols are characterised by poor absorption, rapid degradation and extensive metabolism, culminating in poor bioavailability (~1 µM). In addition, they can also exhibit paradoxical pro-oxidant activities. Spectrophotometric and mass spectrometry (LC-MS/MS) analysis of the phenolic compound, delphinidin, confirmed its low stability and rapid degradation (t 1 / 2 ~30 min) under physiologically relevant conditions. Delphinidin degraded to smaller phenolics: gallic acid and phloroglucinol aldehyde. Moreover, both the parent compound and its main metabolite, gallic acid, generated oxygen-centred free radicals at concentrations≥10 µM, as determined by electron paramagnetic resonance spectrometry (EPR). Interestingly, the tested phenolics offered significant protection to human umbilical endothelial cells (HUVECs) against chemically induced oxidative stress. The protective effect of both phenolics were hormesic in profile; supraphysiological concentrations (100 µM) were cytotoxic, whereas physiologically relevant concentrations (100 nM – 1 µM) were protective against oxidative stress. The observed protection was associated with increased intracellular glutathione. The results confirm that physiologically relevant concentrations of delphinidin and its major metabolite, gallic acid, are sufficient to induce antioxidant benefits, but via an indirect, xenobiotic mechanism that induces upregulation of endogenous antioxidant capacity. The findings emphasis that stability, rate of absorption, distribution and metabolism of phenolic compound needs to be taken into consideration when designing in vitro studies to test their mechanism of action.