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Advances in Nutrition (Bethesda, Md.) Nov 2019The aging population is expanding, as is the prevalence of age-related cognitive decline (ARCD). Of the several risk factors that predict the onset and progression of... (Review)
Review
The aging population is expanding, as is the prevalence of age-related cognitive decline (ARCD). Of the several risk factors that predict the onset and progression of ARCD, 2 important modifiable risk factors are diet and physical activity. Dietary patterns that emphasize plant foods can exert neuroprotective effects. In this comprehensive review, we examine studies in humans of plant-based dietary patterns and polyphenol-rich plant foods and their role in either preventing ARCD and/or improving cognitive function. As yet, there is no direct evidence to support the benefits of a vegetarian diet in preventing cognitive decline. However, there is emerging evidence for brain-health-promoting effects of several plant foods rich in polyphenols, anti-inflammatory dietary patterns, and plant-based dietary patterns such as the Mediterranean diet that include a variety of fruits, vegetables, legumes, nuts, and whole grains. The bioactive compounds present in these dietary patterns include antioxidant vitamins, polyphenols, other phytochemicals, and unsaturated fatty acids. In animal models these nutrients and non-nutrients have been shown to enhance neurogenesis, synaptic plasticity, and neuronal survival by reducing oxidative stress and neuroinflammation. In this review, we summarize the mounting evidence in favor of plant-centered dietary patterns, inclusive of polyphenol-rich foods for cognitive well-being. Randomized clinical trials support the role of plant foods (citrus fruits, grapes, berries, cocoa, nuts, green tea, and coffee) in improving specific domains of cognition, most notably frontal executive function. We also identify knowledge gaps and recommend future studies to identify whether plant-exclusive diets have an added cognitive advantage compared with plant-centered diets with fish and/or small amounts of animal foods.
Topics: Animals; Antioxidants; Cognition; Cognitive Dysfunction; Diet, Mediterranean; Diet, Vegetarian; Executive Function; Feeding Behavior; Humans; Neurogenesis; Neuroprotective Agents; Plants; Polyphenols
PubMed: 31728502
DOI: 10.1093/advances/nmz081 -
Cancer Discovery Apr 2022Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show...
UNLABELLED
Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/FOXP3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine-conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance.
SIGNIFICANCE
The polyphenol castalagin isolated from a berry has an antitumor effect through direct interactions with commensal bacteria, thus reprogramming the tumor microenvironment. In addition, in preclinical ICI-resistant models, castalagin reestablishes the efficacy of anti-PD-1. Together, these results provide a strong biological rationale to test castalagin as part of a clinical trial. This article is highlighted in the In This Issue feature, p. 873.
Topics: Animals; Bacteria; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Mice; Polyphenols
PubMed: 35031549
DOI: 10.1158/2159-8290.CD-21-0808 -
Molecules (Basel, Switzerland) Apr 2021Polyphenols are classified as an organic chemical with phenolic units that display an array of biological functions. However, polyphenols have very low bioavailability... (Review)
Review
Polyphenols are classified as an organic chemical with phenolic units that display an array of biological functions. However, polyphenols have very low bioavailability and stability, which make polyphenols a less bioactive compound. Many researchers have indicated that several factors might affect the efficiency and the metabolism (biotransformation) of various polyphenols, which include the gut microbiota, structure, and physical properties as well as its interactions with other dietary nutrients (macromolecules). Hence, this mini-review covers the two-way interaction between polyphenols and gut microbiota (interplay) and how polyphenols are metabolized (biotransformation) to produce various polyphenolic metabolites. Moreover, the protective effects of numerous polyphenols and their metabolites against various gastrointestinal disorders/diseases including gastritis, gastric cancer, colorectal cancer, inflammatory bowel disease (IBD) like ulcerative colitis (UC), Crohn's disease (CD), and irritable bowel syndrome (IBS) like celiac disease (CED) are discussed. For this review, the authors chose only a few popular polyphenols (green tea polyphenol, curcumin, resveratrol, quercetin), and a discussion of their proposed mechanism underpinning the gastroprotection was elaborated with a special focus on clinical evidence. Overall, this contribution would help the general population and science community to identify a potent polyphenol with strong antioxidant, anti-inflammatory, anti-cancer, prebiotic, and immunomodulatory properties to combat various gut-related diseases or disorders (complementary therapy) along with modified lifestyle pattern and standard gastroprotective drugs. However, the data from clinical trials are much limited and hence many large-scale clinical trials should be performed (with different form/metabolites and dose) to confirm the gastroprotective activity of the above-mentioned polyphenols and their metabolites before recommendation.
Topics: Animals; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Metabolome; Polyphenols; Protective Agents; Stomach
PubMed: 33917379
DOI: 10.3390/molecules26072090 -
Biomolecules Dec 2021Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both... (Review)
Review
Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., , , , , , , , and as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through molecular modeling. , , Studio, and have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.
Topics: Computer Simulation; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Gene Expression Regulation, Enzymologic; Glycoside Hydrolase Inhibitors; Humans; Hydrogen Bonding; Hypoglycemic Agents; Molecular Docking Simulation; Plants, Medicinal; Polyphenols; alpha-Amylases; alpha-Glucosidases
PubMed: 34944521
DOI: 10.3390/biom11121877 -
Nutrients Aug 2020Curcumin, a lipophilic polyphenol contained in the rhizome of (turmeric), has been used for centuries in traditional Asian medicine, and nowadays it is widely used in... (Review)
Review
Curcumin, a lipophilic polyphenol contained in the rhizome of (turmeric), has been used for centuries in traditional Asian medicine, and nowadays it is widely used in food as dietary spice worldwide. It has received considerable attention for its pharmacological activities, which appear to act primarily through anti-inflammatory and antioxidant mechanisms. For this reason, it has been proposed as a tool for the management of many diseases, among which are gastrointestinal and neurological diseases, diabetes, and several types of cancer. However, the pharmacology of curcumin remains to be elucidated; indeed, a discrepancy exists between the well-documented in vitro and in vivo activities of curcumin and its poor bioavailability and chemical instability that should limit any therapeutic effect. Recently, it has been hypothesized that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of this polyphenol have been detected after oral administration. Consequently, it might be hypothesized that curcumin directly exerts its regulatory effects on the gut microbiota, thus explaining the paradox between its low systemic bioavailability and its wide pharmacological activities. It is well known that the microbiota has several important roles in human physiology, and its composition can be influenced by a multitude of environmental and lifestyle factors. Accordingly, any perturbations in gut microbiome profile or dysbiosis can have a key role in human disease progression. Interestingly, curcumin and its metabolites have been shown to influence the microbiota. It is worth noting that from the interaction between curcumin and microbiota two different phenomena arise: the regulation of intestinal microflora by curcumin and the biotransformation of curcumin by gut microbiota, both of them potentially crucial for curcumin activity. This review summarizes the most recent studies on this topic, highlighting the strong connection between curcumin and gut microbiota, with the final aim of adding new insight into the potential mechanisms by which curcumin exerts its effects.
Topics: Anti-Inflammatory Agents; Antioxidants; Biotransformation; Curcumin; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Polyphenols
PubMed: 32824993
DOI: 10.3390/nu12092499 -
Nutrients Aug 2023It is well known that neurodegenerative diseases' development and progression are accelerated due to oxidative stress and inflammation, which result in impairment of... (Review)
Review
It is well known that neurodegenerative diseases' development and progression are accelerated due to oxidative stress and inflammation, which result in impairment of mitochondrial function, cellular damage, and dysfunction of DNA repair systems. The increased consumption of antioxidants can postpone the development of these disorders and improve the quality of patients' lives who have already been diagnosed with neurodegenerative diseases. Prolonging life span in developed countries contributes to an increase in the incidence ratio of chronic age-related neurodegenerative disorders, such as PD (Parkinson's disease), AD (Alzheimer's disease), or numerous forms of age-related dementias. Dietary supplementation with neuroprotective plant-derived polyphenols might be considered an important element of healthy aging. Some polyphenols improve cognition, mood, visual functions, language, and verbal memory functions. Polyphenols bioavailability differs greatly from one compound to another and is determined by solubility, degree of polymerization, conjugation, or glycosylation resulting from chemical structure. It is still unclear which polyphenols are beneficial because their potential depends on efficient transport across the BBB (blood-brain barrier), bioavailability, and stability in the CNS (central nervous system). Polyphenols improve brain functions by having a direct impact on cells and processes in the CNS. For a direct effect, polyphenolic compounds must be able to overcome the BBB and accumulate in brain tissue. In this review, the latest achievements in studies (animal models and clinical trials) on the effect of polyphenols on brain activity and function are described. The beneficial impact of plant polyphenols on the brain may be summarized by their role in increasing brain plasticity and related cognition improvement. As reversible MAO (monoamine oxidase) inhibitors, polyphenols are mood modulators and improve neuronal self-being through an increase in dopamine, serotonin, and noradrenaline amounts in the brain tissue. After analyzing the prohealth effects of various eating patterns, it was postulated that their beneficial effects result from synergistic interactions between individual dietary components. Polyphenols act on the brain endothelial cells and improve the BBB's integrity and reduce inflammation, thus protecting the brain from additional injury during stroke or autoimmune diseases. Polyphenolic compounds are capable of lowering blood pressure and improving cerebral blood flow. Many studies have revealed that a nutritional model based on increased consumption of antioxidants has the potential to ameliorate the cognitive impairment associated with neurodegenerative disorders. Randomized clinical trials have also shown that the improvement of cognitive functions resulting from the consumption of foods rich in flavonoids is independent of age and health conditions. For therapeutic use, sufficient quantities of polyphenols must cross the BBB and reach the brain tissue in active form. An important issue in the direct action of polyphenols on the CNS is not only their penetration through the BBB, but also their brain metabolism and localization. The bioavailability of polyphenols is low. The most usual oral administration also conflicts with bioavailability. The main factors that limit this process and have an effect on therapeutic efficacy are: selective permeability across BBB, gastrointestinal transformations, poor absorption, rapid hepatic and colonic metabolism, and systemic elimination. Thus, phenolic compounds have inadequate bioavailability for human applications to have any beneficial effects. In recent years, new strategies have been attempted in order to exert cognitive benefits and neuroprotective effects. Converting polyphenols into nanostructures is one of the theories proposed to enhance their bioavailability. The following nanoscale delivery systems can be used to encapsulate polyphenols: nanocapsules, nanospheres, micelles, cyclodextrins, solid lipid nanoparticles, and liposomes. It results in great expectations for the wide-scale and effective use of polyphenols in the prevention of neurodegenerative diseases. Thus far, only natural polyphenols have been studied as neuroprotectors. Perhaps some modification of the chemical structure of a given polyphenol may increase its neuroprotective activity and transportation through the BBB. However, numerous questions should be answered before developing neuroprotective medications based on plant polyphenols.
Topics: Animals; Humans; Polyphenols; Neurodegenerative Diseases; Antioxidants; Endothelial Cells; Inflammation
PubMed: 37571391
DOI: 10.3390/nu15153454 -
Nutrients Nov 2020Increasing evidence support a beneficial role of cocoa and cocoa products on human cognition, particularly in aging populations and patients at risk. However, thorough...
Increasing evidence support a beneficial role of cocoa and cocoa products on human cognition, particularly in aging populations and patients at risk. However, thorough reviews on the efficacy of cocoa on brain processes in young adults do not exist precisely due to the limited number of studies in the matter. Thus, the aim of this study was to summarize the findings on the acute and chronic effects of cocoa administration on cognitive functions and brain health in young adults. Web of Science and PubMed databases were used to search for relevant trials. Human randomized controlled studies were selected according to PRISMA guidelines. Eleven intervention studies that involved a total of 366 participants investigating the role of cocoa on cognitive performance in children and young adults (average age ≤ 25 years old) were finally selected. Findings from individual studies confirm that acute and chronic cocoa intake have a positive effect on several cognitive outcomes. After acute consumption, these beneficial effects seem to be accompanied with an increase in cerebral blood flow or cerebral blood oxygenation. After chronic intake of cocoa flavanols in young adults, a better cognitive performance was found together with increased levels of neurotrophins. This systematic review further supports the beneficial effect of cocoa flavanols on cognitive function and neuroplasticity and indicates that such benefits are possible in early adulthood.
Topics: Adult; Blood Pressure; Brain; Cacao; Cardiovascular System; Cerebrovascular Circulation; Chocolate; Cognition; Endpoint Determination; Flavonols; Humans; Polyphenols; Young Adult
PubMed: 33265948
DOI: 10.3390/nu12123691 -
Chemical & Pharmaceutical Bulletin 2020Black tea accounts for 70-80% of world tea production, and the polyphenols therein are produced by enzymatic oxidation of four tea catechins during tea fermentation.... (Review)
Review
Black tea accounts for 70-80% of world tea production, and the polyphenols therein are produced by enzymatic oxidation of four tea catechins during tea fermentation. However, only limited groups of dimeric oxidation products, such as theaflavins, theasinensins, and theacitrins, have been isolated from black tea and chemically characterized. This is largely because of the complexity and heterogeneity of the oxidation products. To determine structures and production mechanisms of uncharacterized black tea polyphenols, in vitro model fermentation experiments using pure catechins and polyphenol oxidase have been applied, and basic oxidation mechanisms have been established. Contemporary methods, such as LC-MS, are also effective to identify catechin oxidation products in black tea. Despite ongoing efforts, almost 60% of the solids in black tea infusion remain uncharacterized. These compounds include the so-called thearubigins, which are a heterogeneous mixture of uncharacterized catechin oxidation products with oligomeric structures. This review summarizes the current knowledge of the production mechanisms of representative black tea polyphenols and presents recent progress in characterization of thearubigins.
Topics: Molecular Structure; Polyphenols; Tea
PubMed: 33268645
DOI: 10.1248/cpb.c20-00295 -
Nutrients Feb 2020Polyphenols are a class of well-known bioactive compounds widely distributed in the plant kingdom and abundant in plant foods and derived food products [...].
Polyphenols are a class of well-known bioactive compounds widely distributed in the plant kingdom and abundant in plant foods and derived food products [...].
Topics: Diet; Humans; Plant Extracts; Polyphenols
PubMed: 32028558
DOI: 10.3390/nu12020400 -
Molecules (Basel, Switzerland) Dec 2022Polyphenols are secondary metabolites produced by plants, which contribute to the plant's defense against abiotic stress conditions (e.g., UV radiation and... (Review)
Review
Polyphenols are secondary metabolites produced by plants, which contribute to the plant's defense against abiotic stress conditions (e.g., UV radiation and precipitation), the aggression of herbivores, and plant pathogens. Epidemiological studies suggest that long-term consumption of plant polyphenols protects against cardiovascular disease, cancer, osteoporosis, diabetes, and neurodegenerative diseases. Their structural diversity has fascinated and confronted analytical chemists on how to carry out unambiguous identification, exhaustive recovery from plants and organic waste, and define their nutritional and biological potential. The food, cosmetic, and pharmaceutical industries employ polyphenols from fruits and vegetables to produce additives, additional foods, and supplements. In some cases, nanocarriers have been used to protect polyphenols during food processing, to solve the issues related to low water solubility, to transport them to the site of action, and improve their bioavailability. This review summarizes the structure-bioactivity relationships, processing parameters that impact polyphenol stability and bioavailability, the research progress in nanocarrier delivery, and the most innovative methodologies for the exhaustive recovery of polyphenols from plant and agri-waste materials.
Topics: Polyphenols; Dietary Supplements; Fruit; Antioxidants; Vegetables; Plants
PubMed: 36557912
DOI: 10.3390/molecules27248777