Food-derived Polyphenols Research Articles

Co-assembled whey protein and proanthocyanidins as a promising biocarrier for hydrophobic pterostilbene: Fabrication, characterization, and cellular antioxidant potential

The usage of food-derived polyphenols with different polarities has been limited by their instability and incompatibility. Therefore, a biocarrier was developed by co-assembly of whey protein isolate (WPI) and hydrophilic proanthocyanidin (PC) for loading hydrophobic pterostilbene (PTE). Such biocarrier has superior affinity for PTE than WPI alone, as determined by encapsulation efficiency and loading capacity assay, fluorescence quenching analysis, and molecular docking, whereas the assembly process was characterized by particle size and zeta potential, 3-dimensional fluorescence, and scanning electron microscopy. Circular dichroism and Fourier transform infrared spectroscopy spectra confirmed the α-helix to β-sheet and random coil transition of proteins during the formation of nanocomplexes. Whey protein isolate acted as a mediator through altering the binding mode of PC and PTE, allowing them to perform significant synergistic effects in enhancing 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging and reducing H2O2-induced cell damage. This research may serve to develop new protein/polyphenol co-loading systems and offer a reliable nutritional fortification.

Insights on Dietary Polyphenols as Agents against Metabolic Disorders: Obesity as a Target Disease.

Obesity is a condition that leads to increased health problems associated with metabolic disorders. Synthetic drugs are available for obesity treatment, but some of these compounds have demonstrated considerable side effects that limit their use. Polyphenols are vital phytonutrients of plant origin that can be incorporated as functional food ingredients. This review presents recent developments in dietary polyphenols as anti-obesity agents. Evidence supporting the potential application of food-derived polyphenols as agents against obesity has been summarized. Literature evidence supports the effectiveness of plant polyphenols against obesity. The anti-obesity mechanisms of polyphenols have been explained by their potential to inhibit obesity-related digestive enzymes, modulate neurohormones/peptides involved in food intake, and their ability to improve the growth of beneficial gut microbes while inhibiting the proliferation of pathogenic ones. Metabolism of polyphenols by gut microbes produces different metabolites with enhanced biological properties. Thus, research demonstrates that dietary polyphenols can offer a novel path to developing functional foods for treating obesity. Upcoming investigations need to explore novel techniques, such as nanocarriers, to improve the content of polyphenols in foods and their delivery and bioavailability at the target sites in the body.

Identification and Functional Evaluation of Polyphenols That Induce Regulatory T Cells.

Regulatory T cells (Tregs) and CD4+/CD25+ T cells play an important role in the suppression of excessive immune responses, homeostasis of immune function, and oral tolerance. In this study, we screened for food-derived polyphenols that induce Tregs in response to retinaldehyde dehydrogenase (RALDH2) activation using macrophage-like THP-1 cells. THP-1 cells were transfected with an EGFP reporter vector whose expression is regulated under the control of mouse Raldh2 promoter and named THP-1 (Raldh2p-EGFP) cells. The THP-1 (Raldh2p-EGFP) cells were treated with 33 polyphenols after inducing their differentiation into macrophage-like cells using phorbol 12-myristate 13-acetate. Of the 33 polyphenols, five (kaempferol, quercetin, morin, luteolin and fisetin) activated Raldh2 promoter activity, and both quercetin and luteolin activated the endogenous Raldh2 mRNA expression and enzymatic activity. Furthermore, these two polyphenols increased transforming growth factor beta 1 and forkhead box P3 mRNA expression, suggesting that they have Treg-inducing ability. Finally, we verified that these polyphenols could induce Tregs in vivo and consequently induce IgA production. Oral administration of quercetin and luteolin increased IgA production in feces of mice. Therefore, quercetin and luteolin can induce Tregs via RALDH2 activation and consequently increase IgA production, suggesting that they can enhance intestinal barrier function.

Antibacterial activities of polyphenols against foodborne pathogens and their application as antibacterial agents.

Polyphenols are secondary metabolites produced in higher plants. They are known to possess various functional properties in the human body. Polyphenols also exhibit antibacterial activities against foodborne pathogens. Their antibacterial mechanism is based on inhibiting bacterial biofilm formation or inactivating enzymes. Food-derived polyphenols with such antibacterial activity are natural preservatives and can be used as an alternative to synthetic preservatives that can cause side effects, such as allergies, asthma, skin irritation, and cancer. Studies have reported that polyphenols have positive effects, such as decreasing harmful bacteria and increasing beneficial bacteria in the human gut microbiota. Polyphenols can also be used as natural antibacterial agents in food packaging system in the form of emitting sachets, absorbent pads, and edible coatings. We summarized the antibacterial activities, mechanisms and applications of polyphenols as antibacterial agents against foodborne bacteria.

Effects and underlying mechanisms of food polyphenols in treating gouty arthritis: A review on nutritional intake and joint health.

Gouty arthritis, one of the most severe and common forms of arthritis, is characterized by monosodium urate crystal deposition in joints and surrounding tissues. Epidemiological evidence indicates that gouty arthritis incidence is sharply rising globally. Polyphenols are found in many foods and are secondary metabolites in plant foods. The anti-inflammatory and antioxidant effects of food polyphenols have been extensively studied in many inflammatory chronic diseases. Research has suggested that many food polyphenols have excellent anti-gouty arthritis effects. The mechanisms mainly include (a) inhibiting xanthine oxidase activity; (b) reducing the levels of inflammatory cytokines and chemokines; (c) inhibiting the activation of signaling pathways and the NLRP3 inflammasome; and (d) reducing oxidative stress. This paper reviews the research progress and pathogenesis of gouty arthritis and introduces the mechanisms of food polyphenols in treating gouty arthritis, which aims to explore the potential of functional foods in the treatment of gouty arthritis. PRACTICAL APPLICATIONS: The incidence rate of gouty arthritis has increased sharply worldwide, which has seriously affected people's quality of life. According to the current research progress, food polyphenols alleviate gouty arthritis through anti-inflammatory and antioxidant effects. This paper reviews the research progress and molecular pathogenesis of gouty arthritis and introduces the mechanisms of food-derived polyphenols in the treatment of gouty arthritis, which is helpful to the prevention and treatment of gouty arthritis.

Molecular Mechanism of Food-Derived Polyphenols on PD-L1 Dimerization: A Molecular Dynamics Simulation Study.

In cancer immunotherapy, an emerging approach is to block the interactions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) using small-molecule inhibitors. The food-derived polyphenols curcumin (CC), resveratrol (RSV) and epigallocatechin gallate (EGCG) have anticancer immunologic functions, which, recently, have been proposed to act via the downregulation of PD-L1 expression. However, it remains unclear whether they can directly target PD-L1 dimerization and, thus, interrupt the PD-1/PD-L1 pathway. To elucidate the molecular mechanism of such compounds on PD-L1 dimerization, molecular docking and nanosecond molecular dynamics simulations were performed. Binding free energy calculations show that the affinities of CC, RSV and EGCG to the PD-L1 dimer follow a trend of CC > RSV > EGCG. Hence, CC is the most effective inhibitor of the PD-1/PD-L1 pathway. Analysis on contact numbers, nonbonded interactions and residue energy decomposition indicate that such compounds mainly interact with the C-, F- and G-sheet fragments of the PD-L1 dimer, which are involved in interactions with PD-1. More importantly, nonpolar interactions between these compounds and the key residues Ile54, Tyr56, Met115, Ala121 and Tyr123 play a dominant role in binding. Free energy landscape and secondary structure analyses further demonstrate that such compounds can stably interact with the binding domain of the PD-L1 dimer. The results provide evidence that CC, RSV and EGCG can inhibit PD-1/PD-L1 interactions by directly targeting PD-L1 dimerization. This provides a novel approach to discovering food-derived small-molecule inhibitors of the PD-1/PD-L1 pathway with potential applications in cancer immunotherapy.

Detection and Visualization of Food-derived Polyphenols by Matrix-assisted Laser Desorption/Ionization Mass Spectrometry Imaging

Detection and Visualization of Food-derived Polyphenols by Matrix-assisted Laser Desorption/Ionization Mass Spectrometry Imaging

Enhancing the Cancer Cell Growth Inhibitory Effects of Table Grape Anthocyanins.

Chemical components of grapes are good for our health and have been shown to lower risk for certain cancers. Their beneficial health effects could also be enhanced by consuming other molecules that improve their bioavailability.

Food-derived polyphenols inhibit the growth of ovarian cancer cells irrespective of their ability to induce antioxidant responses

The use of plant polyphenols to prevent cancer has been studied extensively. However, recent findings regarding the cancer-promoting effects of some antioxidants have led to reservations regarding the therapeutic use of food-derived antioxidants including polyphenols. The aim of this study was to evaluate the therapeutic potential of food-derived polyphenols and their use and safety in cancer patients. The free-radical scavenging ability of sulforaphane and various food-derived polyphenols including curcumin, epigallocatechin gallate, epicatechin, pelargonidin, and resveratrol was compared with their growth inhibitory effect on ovarian cancer cells. Oxidative stress and/or antioxidant responses and anti-proliferative pathways were evaluated after administering sulforaphane and polyphenols at doses at which they have been shown to inhibit the growth of ovarian cancer cells. No correlation was observed between their ability to scavenge free radicals and their ability to inhibit the growth of ovarian cancer cells. With the exception of epigallocatechin gallate, all of the antioxidants that were tested at doses that inhibited cell growth significantly increased NAD(P)H quinone dehydrogenase I (NQO1) expression but induced cell cycle arrest and/or apoptotic signaling. Epigallocatechin gallate exhibited a higher free radical scavenging activity but did not induce NQO1 expression at either the mRNA or at the protein level. Treatment with polyphenols at physiological doses did not significantly alter the growth of ovarian cancer cells or NQO1 expression. Therefore, individual food-derived polyphenols appear to have different anti-cancer mechanisms. Their modes of action in relation to their chemical properties should be established, rather than collectively avoiding the use of these agents as antioxidants.

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.

TriCurin, a novel formulation of curcumin, epicatechin gallate, and resveratrol, inhibits the tumorigenicity of human papillomavirus-positive head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and epicatechin gallate from green tea. Cell viability, clonogenic survival, and tumorsphere formation were inhibited and significant apoptosis was induced by TriCurin in UMSCC47 and UPCI:SCC090 HPV-positive HNSCC cells. Moreover, TriCurin decreased HPV16E6 and HPV16E7 and increased p53 levels. In a pre-clinical animal model of HPV-positive HNSCC, intra-tumoral injection of TriCurin significantly inhibited tumor growth by 85.5% compared to vehicle group (P < 0.05, n = 7). Our results demonstrate that TriCurin is a potent anti-tumor agent for HPV-positive HNSCC. Further development of TriCurin as a novel anti-cancer therapeutic to manage the HPV-positive HNSCC population is warranted.

Impact of Dietary Antioxidants on Sport Performance: A Review

Many athletes supplement with antioxidants in the belief this will reduce muscle damage, immune dysfunction and fatigue, and will thus improve performance, while some evidence suggests it impairs training adaptations. Here we review the effect of a range of dietary antioxidants and their effects on sport performance, including vitamin E, quercetin, resveratrol, beetroot juice, other food-derived polyphenols, spirulina and N-acetylcysteine (NAC). Older studies suggest vitamin E improves performance at altitude, with possible harmful effects on sea-level performance. Acute intake of vitamin E is worthy of further consideration, if plasma levels can be elevated sufficiently. Quercetin has a small beneficial effect for exercise of longer duration (>100 min), but it is unclear whether this benefits athletes. Resveratrol benefits trained rodents; more research is needed in athletes. Meta-analysis of beetroot juice studies has revealed that the nitrate component of beetroot juice had a substantial but unclear effect on performance when averaged across athletes, non-athletes and modes of exercise (single dose 1.4 ± 2.0%, double dose 0.5 ± 1.9%). The effect of addition of polyphenols and other components to beetroot juice was trivial but unclear (single dose 0.4 ± 3.2%, double dose -0.5 ± 3.3%). Other food-derived polyphenols indicate a range of performance outcomes from a large improvement to moderate impairment. Limited evidence suggests spirulina enhances endurance performance. Intravenous NAC improved endurance cycling performance and reduced muscle fatigue. On the basis of vitamin E and NAC studies, acute intake of antioxidants is likely to be beneficial. However, chronic intakes of most antioxidants have a harmful effect on performance.

Malvidin, a red wine polyphenol, modulates mammalian myocardial and coronary performance and protects the heart against ischemia/reperfusion injury

A moderate red wine consumption and a colored fruit-rich diet protect the cardiovascular system, thanks to the presence of several polyphenols. Malvidin-3-0-glucoside (malvidin), an anthocyanidine belonging to polyphenols, is highly present in red grape skin and red wine. Its biological activity is poorly characterized, although a role in tumor cell inhibition has been found. To analyze whether and to which extent, like other food-derived polyphenols, malvidin affects the cardiovascular function, in this study, we have performed a quantitative analysis by high-performance liquid chromatography of polyphenolic content of red grape skins extract, showing that it contains a high malvidin amount (63.93±12.50 mg/g of fresh grape skin). By using the isolated and Langendorff perfused rat heart, we found that the increasing doses (1–1000 ng/ml) of the extract induced positive inotropic and negative lusitropic effects associated with coronary dilation. On the same cardiac preparations, we observed that malvidin (10−10–10−6 mol/L) elicited negative inotropism and lusitropism and coronary dilation. Analysis of mechanism of action revealed that malvidin-dependent cardiac effects require the activation of the phosphatidylinositol 3-kinase (PI3K)/nitric oxide (NO)/cGMP/PKG pathway and are associated with increased intracellular cGMP and the phosphorylation of endothelial NO synthase (eNOS), PI3K–AKT, ERK1/2, and GSK-3β. AKT and eNOS phosphorylation was confirmed in human umbilical vein endothelial cell. We also found that malvidin act as a postconditioning agent, being able to elicit cardioprotection against ischemia/reperfusion damages. Our results show the cardioactivity of polyphenols-rich red grape extracts and indicate malvidin as a new cardioprotective principle. This is of relevance not only for a better clarification of the beneficial cardiovascular effects of food-derived polyphenols but also for nutraceutical research.

Immunochemical Detection of Food-Derived Polyphenols in the Aorta: Macrophages as a Major Target Underlying the Anti-Atherosclerotic Activity of Polyphenols

It has been suggested that polyphenol-rich diets decrease the risk of cardiovascular diseases. Although studies of the bioavailability of polyphenols, particularly their absorption and metabolism, have been reported recently, the tissue and cellular distributions underlying their biological mechanisms remain unknown. It is difficult to evaluate the specific localization of tissue and/or cellular polyphenols, because the method is limited to chromatography. To overcome these difficulties, we have developed anti-polyphenol antibodies to characterize immunohistochemically the localization of polyphenols and their metabolites in vivo. Two novel monoclonal antibodies were raised against quercetin and tea catechins, which represent flavonoid-type polyphenols distributed in foods and beverages, and are expected to exhibit anti-oxidative and anti-inflammatory activities in vivo. Using these antibodies, we identified activated macrophages as a specific target of these flavonoids during the development of atherosclerotic lesions. This review describes recent findings on the molecular actions of flavonoids that underly their anti-atherosclerotic activity in vivo.

Polyphenols as Potential Inhibitors of Amyloid Aggregation and Toxicity:Possible Significance to Alzheimers Disease

Beta-amyloid (Abeta)likely plays a pivotal role in the etiology of Alzheimer's disease (AD). Consequently, Abeta associated pathways are targets for the development of possible effective AD therapies. This review first updates strategies aimed at the inhibition of Abeta formation and then discusses the role of food-derived polyphenols as putative anti-amyloid drugs.

Comparative Effects of Food-Derived Polyphenols on the Viability and Apoptosis of a Human Hepatoma Cell Line (HepG2)

Consumption of fruits and vegetables, which are rich in polyphenols, has been associated with a reduced risk of chronic diseases such as cancer. Dietary polyphenols have antioxidant and antiproliferative properties that might explain their beneficial effect on cancer prevention. The aim of this study was to investigate the effects of different pure polyphenols [quercetin, chlorogenic acid, and (-)-epicatechin] and natural fruit extracts (strawberry and plum) on viability or apoptosis of human hepatoma HepG2 cells. The treatment of cells for 18 h with quercetin and fruit extracts reduced cell viability in a dose-dependent manner; however, chlorogenic acid and (-)-epicatechin had no prominent effects on the cell death rate. Similarly, quercetin and strawberry and plum extracts, rather than chlorogenic acid and (-)-epicatechin, induced apoptosis in HepG2 cells. Moreover, quercetin and fruit extracts arrested the G1 phase in the cell cycle progression prior to apoptosis. Quercetin and strawberry and plum extracts may induce apoptosis and contribute to a reduced cell viability in HepG2 cells.

Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis.

There is increasing evidence that food-derived polyphenols have a beneficial effect for cancers. Our purpose was to determine the effect and mechanism of action of these compounds on pancreatic cancer. We measured effects of quercetin on pancreatic cancer in a nude mouse model. We also investigated the effects of quercetin, rutin, trans-resveratrol and genistein on apoptosis and underlying signaling in pancreatic carcinoma cells in vitro. Quercetin decreased primary tumor growth, increased apoptosis and prevented metastasis in a model of pancreatic cancer. In vitro quercetin and trans-resveratrol, but not rutin, markedly enhanced apoptosis, causing mitochondrial depolarization and cytochrome c release followed by caspase-3 activation. In addition, the effect of a combination of quercetin and trans-resveratrol on mitochondrial cytochrome c release and caspase-3 activity was greater than the expected additive response. The inhibition of mitochondrial permeability transition prevented cytochrome c release, caspase-3 activation and apoptosis caused by polyphenols. Nuclear factor-kappa B activity was inhibited by quercetin and trans-resveratrol, but not genistein, indicating that this transcription factor is not the only mediator of the polyphenols' effects on apoptosis. The results suggest that food-derived polyphenols inhibit pancreatic cancer growth and prevent metastasis by inducing mitochondrial dysfunction, resulting in cytochrome c release, caspase activation and apoptosis.