-
Molecules (Basel, Switzerland) May 2016Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied... (Review)
Review
Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase.
Topics: Antioxidants; Brassica; Flavonols; Histamine; Humans; Immunity, Innate; Immunoglobulin E; Interleukin-4; Onions; Quercetin; Th1-Th2 Balance
PubMed: 27187333
DOI: 10.3390/molecules21050623 -
Oxidative Medicine and Cellular... 2022Plant preparations have been used to treat various diseases and discussed for centuries. Research has advanced to discover and identify the plant components with... (Review)
Review
Plant preparations have been used to treat various diseases and discussed for centuries. Research has advanced to discover and identify the plant components with beneficial effects and reveal their underlying mechanisms. Flavonoids are phytoconstituents with anti-inflammatory, antimutagenic, anticarcinogenic, and antimicrobial properties. Herein, we listed and contextualized various aspects of the protective effects of the flavonols quercetin, isoquercetin, kaempferol, and myricetin and the flavones luteolin, apigenin, 3',4'-dihydroxyflavone, baicalein, scutellarein, lucenin-2, vicenin-2, diosmetin, nobiletin, tangeretin, and 5-O-methyl-scutellarein. We presented their structural characteristics and subclasses, importance, occurrence, and food sources. The bioactive compounds present in our diet, such as fruits and vegetables, may affect the health and disease state. Therefore, we discussed the role of these compounds in inflammation, oxidative mechanisms, and bacterial metabolism; moreover, we discussed their synergism with antibiotics for better disease outcomes. Indiscriminate use of antibiotics allows the emergence of multidrug-resistant bacterial strains; thus, bioactive compounds may be used for adjuvant treatment of infectious diseases caused by resistant and opportunistic bacteria direct and indirect mechanisms. We also focused on the reported mechanisms and intracellular targets of flavonols and flavones, which support their therapeutic role in inflammatory and infectious diseases.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antioxidants; Apigenin; Flavones; Flavonoids; Flavonols; Kaempferols; Luteolin; Plant Preparations; Quercetin
PubMed: 36111166
DOI: 10.1155/2022/9966750 -
International Journal of Molecular... Jun 2019Cancer is a problem with worldwide importance and is the second leading cause of death globally. Cancer cells reprogram their metabolism to support their uncontrolled... (Review)
Review
Cancer is a problem with worldwide importance and is the second leading cause of death globally. Cancer cells reprogram their metabolism to support their uncontrolled expansion by increasing biomass (anabolic metabolism-glycolysis) at the expense of their energy (bioenergetics- mitochondrial function) requirements. In this aspect, metabolic reprogramming stands out as a key biological process in understanding the conversion of a normal cell into a neoplastic precursor. Quercetin is the major representative of the flavonoid subclass of flavonols. Quercetin is ubiquitously present in fruits and vegetables, being one of the most common dietary flavonols in the western diet. The anti-cancer effects of quercetin include its ability to promote the loss of cell viability, apoptosis and autophagy through the modulation of PI3K/Akt/mTOR, Wnt/-catenin, and MAPK/ERK1/2 pathways. In this review, we discuss the role of quercetin in cancer metabolism, addressing specifically its ability to target molecular pathways involved in glucose metabolism and mitochondrial function.
Topics: Animals; Antineoplastic Agents; Apoptosis; Energy Metabolism; Humans; Neoplasms; Quercetin; Signal Transduction
PubMed: 31261749
DOI: 10.3390/ijms20133177 -
Nutrients Sep 2019Fruit and vegetable intake has been associated with a reduced risk of cardiovascular disease. Quercetin and kaempferol are among the most ubiquitous polyphenols in fruit... (Review)
Review
Fruit and vegetable intake has been associated with a reduced risk of cardiovascular disease. Quercetin and kaempferol are among the most ubiquitous polyphenols in fruit and vegetables. Most of the quercetin and kaempferol in plants is attached to sugar moieties rather than in the free form. The types and attachments of sugars impact bioavailability, and thus bioactivity. This article aims to review the current literature on the bioavailability of quercetin and kaempferol from food sources and evaluate the potential cardiovascular effects in humans. Foods with the highest concentrations of quercetin and kaempferol in plants are not necessarily the most bioavailable sources. Glucoside conjugates which are found in onions appear to have the highest bioavailability in humans. The absorbed quercetin and kaempferol are rapidly metabolized in the liver and circulate as methyl, glucuronide, and sulfate metabolites. These metabolites can be measured in the blood and urine to assess bioactivity in human trials. The optimal effective dose of quercetin reported to have beneficial effect of lowering blood pressure and inflammation is 500 mg of the aglycone form. Few clinical studies have examined the potential cardiovascular effects of high intakes of quercetin- and kaempferol-rich plants. However, it is possible that a lower dosage from plant sources could be effective due to of its higher bioavailability compared to the aglycone form. Studies are needed to evaluate the potential cardiovascular benefits of plants rich in quercetin and kaempferol glycoside conjugates.
Topics: Biological Availability; Cardiovascular Diseases; Humans; Kaempferols; Quercetin
PubMed: 31557798
DOI: 10.3390/nu11102288 -
Biomolecules May 2019Despite advancements in healthcare facilities for diagnosis and treatment, cancer remains the leading cause of death worldwide. As prevention is always better than cure,... (Review)
Review
Despite advancements in healthcare facilities for diagnosis and treatment, cancer remains the leading cause of death worldwide. As prevention is always better than cure, efficient strategies are needed in order to deal with the menace of cancer. The use of phytochemicals as adjuvant chemotherapeutic agents in heterogeneous human carcinomas like breast, colon, lung, ovary, and prostate cancers has shown an upward trend during the last decade or so. Flavonoids are well-known products of plant derivatives that are reportedly documented to be therapeutically active phytochemicals against many diseases encompassing malignancies, inflammatory disorders (cardiovascular disease, neurodegenerative disorder), and oxidative stress. The current review focuses on two key flavonols, fisetin and quercetin, known for their potential pharmacological relevance. Also, efforts have been made to bring together most of the concrete studies pertaining to the bioactive potential of fisetin and quercetin, especially in the modulation of a range of cancer signaling pathways. Further emphasis has also been made to highlight the molecular action of quercetin and fisetin so that one could explore cancer initiation pathways and progression, which could be helpful in designing effective treatment strategies.
Topics: Animals; Apoptosis; Chemoprevention; Flavonoids; Flavonols; Humans; Neoplasms; Quercetin; Signal Transduction
PubMed: 31064104
DOI: 10.3390/biom9050174 -
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 -
CNS Neuroscience & Therapeutics Feb 2022Fisetin, the effective ingredient of the traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its...
BACKGROUND
Fisetin, the effective ingredient of the traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its role in sepsis-associated encephalopathy (SAE) remains unclarified.
METHODS
Cecal ligation and puncture (CLP) operation was performed to establish a rat model of SAE. Rats were grouped according to the surgery operation and fisetin administration. Cognitive impairment was assessed by Morris water maze test. Disruption of blood-brain barrier (BBB) integrity was detected by Evan's blue staining. The mitophagy, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation, and pro-inflammatory cytokines levels were measured through western blot and double immunofluorescence labeling. A transmission electron microscope was applied for the observation of mitochondrial autophagosomes.
RESULTS
Rats in the CLP group presented increased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglial cells, indicating severe inflammation in the central nervous system (CNS). Nevertheless, there was no increase in BBB permeability. Meanwhile, NLRP3 inflammasome was activated in cerebral microvascular endothelial cells (CMECs), presented with an elevation of caspase-1 expression and IL-1β secretion into CNS. In addition, we found fisetin significantly improved cognitive dysfunction in rats with SAE. Neuroprotective effects of fisetin might be associated with inhibition of neuroinflammation, represented with decreased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglia. Furthermore, fisetin induced mitophagy, scavenged ROS, blocked NLRP3 inflammasome activation of CMECs, as evidenced by decreased expression of caspase-1 and reduced release of IL-1β into CNS.
CONCLUSION
Collectively, fisetin-blocked NLRP3 inflammasome activation via promoting mitophagy in CMECs may suppress the secretion of IL-1β into CNS, reduce neuroinflammation, and contribute to the amelioration of cognitive impairment.
Topics: Animals; Behavior, Animal; Cognitive Dysfunction; Disease Models, Animal; Flavonols; Inflammasomes; Male; Mitophagy; NLR Family, Pyrin Domain-Containing 3 Protein; Neuroinflammatory Diseases; Neuroprotective Agents; Rats; Sepsis-Associated Encephalopathy
PubMed: 34837343
DOI: 10.1111/cns.13765 -
Cell Metabolism Apr 2021Attenuating pathological angiogenesis in diseases characterized by neovascularization such as diabetic retinopathy has transformed standards of care. Yet little is known...
Attenuating pathological angiogenesis in diseases characterized by neovascularization such as diabetic retinopathy has transformed standards of care. Yet little is known about the molecular signatures discriminating physiological blood vessels from their diseased counterparts, leading to off-target effects of therapy. We demonstrate that in contrast to healthy blood vessels, pathological vessels engage pathways of cellular senescence. Senescent (p16-expressing) cells accumulate in retinas of patients with diabetic retinopathy and during peak destructive neovascularization in a mouse model of retinopathy. Using either genetic approaches that clear p16-expressing cells or small molecule inhibitors of the anti-apoptotic protein BCL-xL, we show that senolysis suppresses pathological angiogenesis. Single-cell analysis revealed that subsets of endothelial cells with senescence signatures and expressing Col1a1 are no longer detected in BCL-xL-inhibitor-treated retinas, yielding a retina conducive to physiological vascular repair. These findings provide mechanistic evidence supporting the development of BCL-xL inhibitors as potential treatments for neovascular retinal disease.
Topics: Animals; Apoptosis; Cellular Senescence; Collagen Type I, alpha 1 Chain; Cyclin-Dependent Kinase Inhibitor p16; Disease Models, Animal; Endothelial Cells; Female; Flavonols; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neovascularization, Pathologic; Retinal Diseases; Tacrolimus; bcl-X Protein
PubMed: 33548171
DOI: 10.1016/j.cmet.2021.01.011 -
Nutrients May 2022Cardiovascular disease (CVD) is the leading cause of deaths globally. The main target for prevention of cardiovascular (CV) risk are lifestyle changes, including... (Review)
Review
Cardiovascular disease (CVD) is the leading cause of deaths globally. The main target for prevention of cardiovascular (CV) risk are lifestyle changes, including particular dietary recommendations, involving high intake of fruits and vegetables. Flavonols are a subgroup of flavonoids-compounds present in fruits, vegetables, and tea-known for their antioxidative properties. There are many findings about the beneficial impact of flavonols on general CV risk and its factors, but mainly from in vitro and animal model studies. This paper summarizes data from human studies about flavonols' impact on general CV risk and its factors. A high dietary intake of flavonols could decrease CVD mortality directly or through impact on selected CV factors; however, available data are inconsistent. Nonetheless, specific groups of patients (smoking men, hypertensive and diabetic patients) can potentially benefit from selected dietary modifications or flavonols (quercetin) supplementation. Future investigations about kaempferol and myricetin are needed.
Topics: Animals; Cardiovascular Diseases; Flavonoids; Flavonols; Heart Disease Risk Factors; Humans; Quercetin; Risk Factors; Vegetables
PubMed: 35565940
DOI: 10.3390/nu14091973 -
Nutrients Mar 2022Flavonols are one of the most plentiful flavonoid subclasses found in natural products and are extensively used as dietary supplements. Numerous in vitro and in vivo... (Review)
Review
Flavonols are one of the most plentiful flavonoid subclasses found in natural products and are extensively used as dietary supplements. Numerous in vitro and in vivo studies have shown the cardioprotective properties of flavonols, especially quercetin. This group of substances exerts positive impacts primarily due to their antiatherogenic, antithrombotic, and antioxidant activities. The potential of flavonols to promote vasodilation and regulation of apoptotic processes in the endothelium are other beneficial effects on the cardiovascular system. Despite promising experimental findings, randomized controlled trials and meta-analyses have yielded inconsistent results on the influence of these substances on human cardiovascular parameters. Thus, this review aims to summarize the most recent clinical data on the intake of these substances and their effects on the cardiovascular system. The present study will help clinicians and other healthcare workers understand the value of flavonol supplementation in both subjects at risk for cardiovascular disease and patients with cardiovascular diseases.
Topics: Antioxidants; Cardiovascular Diseases; Flavonoids; Flavonols; Humans; Quercetin
PubMed: 35406050
DOI: 10.3390/nu14071439