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Phytomedicine : International Journal... Oct 2023Polyphenols are a class of naturally sourced compounds with widespread distribution and an extensive array of bioactivities. However, due to their complex constituents... (Review)
Review
BACKGROUND
Polyphenols are a class of naturally sourced compounds with widespread distribution and an extensive array of bioactivities. However, due to their complex constituents and weak absorption, a convincing explanation for their remarkable bioactivity remains elusive for a long time. In recent years, interaction with gut microbiota is hypothesized to be a reasonable explanation of the potential mechanisms for natural compounds especially polyphenols.
OBJECTIVES
This review aims to present a persuasive explanation for the contradiction between the limited bioavailability and the remarkable bioactivities of polyphenols by examining their interactions with gut microbiota.
METHODS
We assessed literatures published before April 10, 2023, from several databases, including Scopus, PubMed, Google Scholar, and Web of Science. The keywords used include "polyphenols", "gut microbiota", "short-chain fatty acids", "bile acids", "trimethylamine N-oxide", "lipopolysaccharides" "tryptophan", "dopamine", "intestinal barrier", "central nervous system", "lung", "anthocyanin", "proanthocyanidin", "baicalein", "caffeic acid", "curcumin", "epigallocatechin-3-gallate", "ferulic acid", "genistein", "kaempferol", "luteolin", "myricetin", "naringenin", "procyanidins", "protocatechuic acid", "pterostilbene", "quercetin", "resveratrol", etc. RESULTS: The review first demonstrates that polyphenols significantly alter gut microbiota diversity (α- and β-diversity) and the abundance of specific microorganisms. Polyphenols either promote or inhibit microorganisms, with various factors influencing their effects, such as dosage, treatment duration, and chemical structure of polyphenols. Furthermore, the review reveals that polyphenols regulate several gut microbiota metabolites, including short-chain fatty acids, dopamine, trimethylamine N-oxide, bile acids, and lipopolysaccharides. Polyphenols affect these metabolites by altering gut microbiota composition, modifying microbial enzyme activity, and other potential mechanisms. The changed microbial metabolites induced by polyphenols subsequently trigger host responses in various ways, such as acting as intestinal acid-base homeostasis regulators and activating on specific target receptors. Additionally, polyphenols are transformed into microbial derivatives by gut microbiota and these polyphenols' microbial derivatives have many potential advantages (e.g., increased bioactivity, improved absorption). Lastly, the review shows polyphenols maintain intestinal barrier, central nervous system, and lung function homeostasis by regulating gut microbiota.
CONCLUSION
The interaction between polyphenols and gut microbiota provides a credible explanation for the exceptional bioactivities of polyphenols. This review aids our understanding of the underlying mechanisms behind the bioactivity of polyphenols.
Topics: Polyphenols; Gastrointestinal Microbiome; Fatty Acids; Oxides
PubMed: 37552899
DOI: 10.1016/j.phymed.2023.154979 -
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 -
Cell Death & Disease Oct 2023Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how...
Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual phenolic acids affect the interactions between intestinal microbiota and macrophages in the context of inflammatory bowel disease (IBD). Here, we aim to elucidate the mechanism by which phenolic acids alleviate gut inflammation. Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were further performed in mice to investigate the role of the gut microbiota in phenolic acid-mediated protective effect. Colitis severity was evaluated using histological, serological, and immunological measurements. Absence of intestinal microbiota and macrophage deteriorate the epithelial injury in DSS colitis. Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation. However, ferulic acid-mediated reduction of colitis was neutrophil-dependent through diminishing the formation of neutrophil extracellular traps. On the other hand, the beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota. In fact, urolithin A (UroA), a metabolite transformed from ellagic acid by the gut microbiota, was found to alleviate colitis and enhance gut barrier function in an IL22-dependent manner. Overall, our findings demonstrated that the mechanisms by which phenolic acid protected against colitis were resulted from the interaction between gut microbiota and macrophage-neutrophil.
Topics: Mice; Animals; Gastrointestinal Microbiome; Polyphenols; Neutrophils; Ellagic Acid; Colitis; Inflammation; Diet; Macrophages; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal; Colon
PubMed: 37813835
DOI: 10.1038/s41419-023-06190-4 -
Biomolecules Jul 2023Polyphenols are secondary metabolites from plant origin and are shown to possess a wide range of therapeutic benefits. They are also reported as regulators of autophagy,... (Review)
Review
Polyphenols are secondary metabolites from plant origin and are shown to possess a wide range of therapeutic benefits. They are also reported as regulators of autophagy, inflammation and neurodegeneration. The autophagy pathway is vital in degrading outdated organelles, proteins and other cellular wastes. The dysregulation of autophagy causes proteinopathies, mitochondrial dysfunction and neuroinflammation thereby contributing to neurodegeneration. Evidence reveals that polyphenols improve autophagy by clearing misfolded proteins in the neurons, suppress neuroinflammation and oxidative stress and also protect from neurodegeneration. This review is an attempt to summarize the mechanism of action of polyphenols in modulating autophagy and their involvement in pathways such as mTOR, AMPK, SIRT-1 and ERK. It is evident that polyphenols cause an increase in the levels of autophagic proteins such as beclin-1, microtubule-associated protein light chain (LC3 I and II), sirtuin 1 (SIRT1), etc. Although it is apparent that polyphenols regulate autophagy, the exact interaction of polyphenols with autophagy markers is not known. These data require further research and will be beneficial in supporting polyphenol supplementation as a potential alternative treatment for regulating autophagy in neurodegenerative diseases.
Topics: Humans; Neuroinflammatory Diseases; Autophagy; Neurodegenerative Diseases; Beclin-1; Polyphenols
PubMed: 37627261
DOI: 10.3390/biom13081196 -
Current Neuropharmacology 2024Autism spectrum disorder (ASD) includes a heterogeneous group of complex neurodevelopmental disorders characterized by atypical behaviors with two core pathological... (Review)
Review
Autism spectrum disorder (ASD) includes a heterogeneous group of complex neurodevelopmental disorders characterized by atypical behaviors with two core pathological manifestations: deficits in social interaction/communication and repetitive behaviors, which are associated with disturbed redox homeostasis. Modulation of cellular resilience mechanisms induced by low levels of stressors represents a novel approach for the development of therapeutic strategies, and in this context, neuroprotective effects of a wide range of polyphenol compounds have been demonstrated in several in vitro and in vivo studies and thoroughly reviewed. Mushrooms have been used in traditional medicine for many years and have been associated with a long list of therapeutic properties, including antitumor, immunomodulatory, antioxidant, antiviral, antibacterial, and hepatoprotective effects. Our recent studies have strikingly indicated the presence of polyphenols in nutritional mushrooms and demonstrated their protective effects in different models of neurodegenerative disorders in humans and rats. Although their therapeutic effects are exerted through multiple mechanisms, increasing attention is focusing on their capacity to induce endogenous defense systems by modulating cellular signaling processes such as nuclear factor erythroid 2 related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) pathways. Here we discuss the protective role of hormesis and its modulation by hormetic nutrients in ASD.
Topics: Humans; Animals; Antioxidants; Hormesis; Autistic Disorder; Agaricales; Autism Spectrum Disorder; Polyphenols
PubMed: 37592816
DOI: 10.2174/1570159X21666230817085811 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2023Polyphenols are secondary metabolites present in small quantities in plant-based food and beverages, with antioxidant and anti-inflammatory properties. Main groups of...
BACKGROUND AND AIMS
Polyphenols are secondary metabolites present in small quantities in plant-based food and beverages, with antioxidant and anti-inflammatory properties. Main groups of polyphenols include flavonoids, phenolic acids, stilbenes, and lignans, but their association with mortality has barely been examined. We aimed to assess the association between the intake of 23 polyphenol subgroups and all-cause, cardiovascular, and cancer mortality in a representative sample of the Spanish adult population.
METHODS
Population-based cohort study conducted with 12,161 individuals aged 18+ recruited in 2008-2010 and followed-up during a mean of 12.5 years. At baseline, food consumption was obtained with a validated dietary history, and the Phenol-Explorer database was used to estimate polyphenol intake. Associations were examined using Cox regression adjusted for main confounders.
RESULTS
During follow-up, 967 all-cause deaths occurred, 219 were cardiovascular, and 277 cancer. Comparing extreme categories of consumption, hazard ratios (95% CI) of total mortality for subgroups were: dihydroflavonols 0.85 (0.72-1.00; p-trend:0.046); flavonols 0.79 (0.63-0.97; p-trend:0.04); methoxyphenols 0.75 (0.59-0.94; p-trend:0.021); tyrosols 0.80 (0.65-0.98; p-trend:0.044); alkylmethoxyphenols 0.74 (0.59-0.93; p-trend:0.007); hydroxycinnamic acids 0.79 (0.64-0.98; p-trend:0.014); and hydroxyphenilacetic acids 0.82 (0.67-0.99; p-trend:0.064). For cardiovascular mortality, hazard ratios were: methoxyphenols 0.58 (0.38-0.89; p-trend:0.010); alkylmethoxyphenols 0.59 (0.39-0.90; p-trend:0.011); hydroxycinnamic acids 0.63 (0.42-0.94; p-trend:0.020); and hydroxyphenilacetic acids 0.69 (0.48-0.99; p-trend:0.044), when comparing extreme tertiles of consumption. No statistically significant associations were observed for cancer. The main food sources for these polyphenol subgroups were red wine, leafy green vegetables, olive oil, green olives, and coffee (the latter being the major contributor of methoxyphenols, alkylmethoxyphenols, and hydroxycinnamic acids).
CONCLUSIONS
In the Spanish adult population, intake of specific polyphenol subgroups was prospectively associated with a 20% lower all-cause mortality risk. This decrease was mainly due to a 40% lower cardiovascular mortality risk over time.
Topics: Adult; Humans; Polyphenols; Cohort Studies; Coumaric Acids; Spain; Neoplasms; Cardiovascular Diseases; Diet
PubMed: 37290979
DOI: 10.1016/j.clnu.2023.05.020 -
Molecules (Basel, Switzerland) Sep 2023Fruits, vegetables, and other food items contain phytochemicals or secondary metabolites which may be considered non-essential nutrients but have medicinal importance.... (Review)
Review
Fruits, vegetables, and other food items contain phytochemicals or secondary metabolites which may be considered non-essential nutrients but have medicinal importance. These dietary phytochemicals exhibit chemopreventive and therapeutic effects against numerous diseases. Polyphenols are secondary metabolites found in vegetables, fruits, and grains. These compounds exhibit several health benefits such as immune modulators, vasodilators, and antioxidants. This review focuses on recent studies on using dietary polyphenols to treat cardiovascular disorders, atherosclerosis, and vascular endothelium deficits. We focus on exploring the safety of highly effective polyphenols to ensure their maximum impact on cardiac abnormalities and discuss recent epidemiological evidence and intervention trials related to these properties. Kaempferol, quercetin, and resveratrol prevent oxidative stress by regulating proteins that induce oxidation in heart tissues. In addition, polyphenols modulate the tone of the endothelium of vessels by releasing nitric oxide (NO) and reducing low-density lipoprotein (LDL) oxidation to prevent atherosclerosis. In cardiomyocytes, polyphenols suppress the expression of inflammatory markers and inhibit the production of inflammation markers to exert an anti-inflammatory response. Consequently, heart diseases such as strokes, hypertension, heart failure, and ischemic heart disease could be prevented by dietary polyphenols.
Topics: Polyphenols; Heart Failure; Atherosclerosis; Vegetables; Endothelium, Vascular
PubMed: 37687232
DOI: 10.3390/molecules28176403 -
Aging Cell May 2024Senescence is a heterogenous and dynamic process in which various cell types undergo cell-cycle arrest due to cellular stressors. While senescence has been implicated in... (Review)
Review
Senescence is a heterogenous and dynamic process in which various cell types undergo cell-cycle arrest due to cellular stressors. While senescence has been implicated in aging and many human pathologies, therapeutic interventions remain inadequate due to the absence of a comprehensive set of biomarkers in a context-dependent manner. Polyphenols have been investigated as senotherapeutics in both preclinical and clinical settings. However, their use is hindered by limited stability, toxicity, modest bioavailability, and often inadequate concentration at target sites. To address these limitations, nanocarriers such as polymer nanoparticles and lipid vesicles can be utilized to enhance the efficacy of senolytic polyphenols. Focusing on widely studied senolytic agents-specifically fisetin, quercetin, and resveratrol-we provide concise summaries of their physical and chemical properties, along with an overview of preclinical and clinical findings. We also highlight common signaling pathways and potential toxicities associated with these agents. Addressing challenges linked to nanocarriers, we present examples of senotherapeutic delivery to various cell types, both with and without nanocarriers. Finally, continued research and development of senolytic agents and nanocarriers are encouraged to reduce the undesirable effects of senescence on different cell types and organs. This review underscores the need for establishing reliable sets of senescence biomarkers that could assist in evaluating the effectiveness of current and future senotherapeutic candidates and nanocarriers.
Topics: Humans; Polyphenols; Nanoparticles; Senotherapeutics; Drug Carriers; Animals; Cellular Senescence; Quercetin
PubMed: 38685568
DOI: 10.1111/acel.14178 -
Sleep Medicine Reviews Dec 2023Polyphenols are plant compounds with several biological activities. This review aims to summarize current knowledge on the potential role of polyphenols in modulating... (Review)
Review
Polyphenols are plant compounds with several biological activities. This review aims to summarize current knowledge on the potential role of polyphenols in modulating sleep. A total of 28 preclinical studies, 12 intervention studies and four observational studies exploring the role of polyphenol intake on sleep were identified. From animal studies, 26 out of the 28 studies found beneficial effects of polyphenols on sleep architecture. Three out of four human observational studies found a beneficial association between polyphenol intake and sleep parameters. And, among clinical intervention studies, eight from a total of 12 studies found some beneficial effect of polyphenol intake on various sleep parameters, although some discrepancies between studies were found. Overall, emerging evidence suggests a benefit of polyphenol intake on sleep. Several mechanisms of action have been suggested, ranging from effects on neurotransmitters to an action through the gut-brain axis. However, more research in this field is needed, emphasizing the use of nutritional doses in mechanistic studies and interventions targeting participants with sleep problems. This would allow to elucidate whether an additional biological effect of polyphenols is modulation of sleep, a behavior associated with adverse health outcomes.
Topics: Animals; Humans; Polyphenols; Diet; Sleep
PubMed: 37659249
DOI: 10.1016/j.smrv.2023.101844 -
Pharmacology & Therapeutics Aug 2023Beyond their role as emulsifiers of lipophilic compounds, bile acids (BAs) are signaling endocrine molecules that show differential affinity and specificity for a... (Review)
Review
Beyond their role as emulsifiers of lipophilic compounds, bile acids (BAs) are signaling endocrine molecules that show differential affinity and specificity for a variety of canonical and non-canonical BA receptors. Primary BAs (PBAs) are synthesized in the liver while secondary BAs (SBAs) are gut microbial metabolites of PBA species. PBAs and SBAs signal to BA receptors that regulate downstream pathways of inflammation and energy metabolism. Dysregulation of BA metabolism or signaling has emerged as a feature of chronic disease. Dietary polyphenols are non-nutritive plant-derived compounds associated with decreased risk of metabolic syndrome, type-2 diabetes, hepatobiliary and cardiovascular disease. Evidence suggests that the health promoting effects of dietary polyphenols are linked to their ability to alter the gut microbial community, the BA pool, and BA signaling. In this review we provide an overview of BA metabolism and summarize studies that link the cardiometabolic improvements of dietary polyphenols to their modulation of BA metabolism and signaling pathways, and the gut microbiota. Finally, we discuss approaches and challenges in deciphering cause-effect relationships between dietary polyphenols, BAs, and gut microbes.
Topics: Humans; Signal Transduction; Liver; Diabetes Mellitus, Type 2; Bile Acids and Salts; Polyphenols
PubMed: 37268113
DOI: 10.1016/j.pharmthera.2023.108457