Quercetin, a flavonoid compound, was found to inhibit both monophenolase and diphenolase activities of tyrosinase, and its inhibition against diphenolase activity was in a reversible and competitive ...manner with an IC50 value of (3.08±0.74)×10−5molL−1. Quercetin bound to tyrosinase driven by hydrophobic interaction, thereby resulted in a conformational change of tyrosinase and its intrinsic fluorescence quenching. Tyrosinase had one binding site for quercetin with the binding constant in the order of magnitude of 104Lmol−1. The molecular docking revealed that quercetin bound to the active site of tyrosinase and chelated a copper with the 3′, 4′-dihydroxy groups. It can be deduced that the chelation may prevent the entrance of substrate and then inhibit the catalytic activity of tyrosinase. These findings may be helpful to understand the inhibition mechanism of quercetin on tyrosinase and functional research of quercetin in the treatment of pigmentation disorders.
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•Quercetin could inhibit both monophenolase and diphenolase activities of tyrosinase.•Hydrophobic interaction dominated the binding of quercetin to tyrosinase.•The binding of quercetin to tyrosinase induced conformational changes of tyrosinase.•Catechol structure of quercetin chelated the copper in the active site of tyrosinase.
This review discusses the most recent data on the potential of quercetin to confer neuroprotection. Unfortunately, most of the in vitro studies have used quercetin aglycone, which is not detectable ...in the plasma or in the brain after oral intake. Moreover, quercetin metabolites and glycosides seem to be less neuroprotective and penetrate the BBB less efficiently than aglycone. Surprisingly, quercetin has beneficial effects on various in vivo models of neural disorders, particularly in cerebrovascular insults; contrasting data also do exist. This may be due to an increase of BBB permeability, described in many of these animal models, which would facilitate quercetin brain penetration. Although quercetin causes no significant toxicity in several animal studies, the risk for neurotoxicity is not negligible because of its narrow therapeutic dose-range in vitro. Notably, this risk may be even higher in the case of increased quercetin access to the brain, which may occur pathologically or artificially (e.g., by liposomal preparations). Based on the referred literature, we doubt that quercetin possesses any significant efficacy in neurodegenerative disorders. Instead, therapeutic trials should focus more on the quercetin efficacy in cerebrovascular insults rather than neurodegeneration.
The flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) is widely distributed in plants, foods, and beverages. This polyphenol compound exhibits varied biological actions such as antioxidant, ...radical-scavenging, anti-inflammatory, antibacterial, antiviral, gastroprotective, immune-modulator, and finds also application in the treatment of obesity, cardiovascular diseases and diabetes. Besides, quercetin can prevent neurological disorders and exerts protection against mitochondrial damages. Various in vitro studies have assessed the anticancer effects of quercetin, although there are no conclusive data regarding its mode of action. However, low bioavailability, poor aqueous solubility as well as rapid body clearance, fast metabolism and enzymatic degradation hamper the use of quercetin as therapeutic agent, so intense research efforts have been focused on the modification of the quercetin scaffold to obtain analogs with potentially improved properties for clinical applications. This review gives an overview of the developments in the synthesis and anticancer-related activities of quercetin derivatives reported from 2012 to 2016.
In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral ...activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.
•Pharmacological activities and molecular targets of quercetin.•Mechanistic pathways of quercetin for treating different diseases.•Formulation strategies for improving the bioavailability of ...quercetin.
Quercetin is reported to have numerous pharmacological actions, including antidiabetic, anti-inflammatory and anticancer activities. The main mechanism responsible for its pharmacological activities is its ability to quench reactive oxygen species (ROS) and, hence, decrease the oxidative stress responsible for the development of various diseases. Despite its proven therapeutic potential, the clinical use of quercetin remains limited because of its low aqueous solubility, bioavailability, and substantial first-pass metabolism. To overcome this, several novel formulations have been reported. In this review, we focus on the applications of quercetin extract as well as its novel formulations for treating different disorders. We also examine its proposed mechanism of action of quercetin.
•Apple MdUGT75B1 and MdUGT71B1 were identified as key UGTs in flavonol biosynthesis.•MdUGT75B1 was flavonol-specific UGT with UDP-Gal preference.•MdUGT71B1 exhibited UDP-Glc preference toward broader ...flavonoid substrates.
Apple is rich in flavonol glycosides, which are believed to contribute to putative health benefits associated with apple consumption. Glycosylation, catalyzed by uridine diphospho-glycosyltransferases (UGTs), is the last step in flavonol biosynthesis, which confers molecular stability and solubility to the flavonol. In the present study, the involvement of two UGTs, MdUGT75B1 and MdUGT71B1, in flavonol biosynthesis in apple was investigated. The major flavonols are quercetin 3-O-glycosides, and UV-B and blue light treatment significantly enhanced the accumulation of quercetin 3-O-galactoside, quercetin 3-O-glucoside, and kaempferol 3-O-galactoside. Transcript levels of MdUGT75B1 and MdUGT71B1 in fruit subjected to different treatments were correlated well with flavonol accumulation. MdUGT75B1 showed flavonol-specific activity with a preference for UDP-galactose as the sugar donor, while MdUGT71B1 using UDP-glucose exhibited a wider substrate acceptance. Thus, MdUGT75B1 and MdUGT71B1 are key UGTs involved in flavonol biosynthesis and may have important roles in regulating accumulation of these health-promoting bioactive compounds in apple.
The flavonoid quercetin is frequently found in low amounts as a secondary plant metabolite in fruits and vegetables. Isolated quercetin is also marketed as a dietary supplement, mostly as the free ...quercetin aglycone, and frequently in daily doses of up to 1000 mg d–1 exceeding usual dietary intake levels. The present review is dedicated to safety aspects of isolated quercetin used as single compound in dietary supplements. Among the numerous published human intervention studies, adverse effects following supplemental quercetin intake have been rarely reported and any such effects were mild in nature. Published adequate scientific data for safety assessment in regard to the long‐term use (>12 weeks) of high supplemental quercetin doses (≥1000 mg) are currently not available. Based on animal studies involving oral quercetin application some possible critical safety aspects could be identified such as the potential of quercetin to enhance nephrotoxic effects in the predamaged kidney or to promote tumor development especially in estrogen‐dependent cancer. Furthermore, animal and human studies with single time or short‐term supplemental quercetin application revealed interactions between quercetin and certain drugs leading to altered drug bioavailability. Based on these results, some potential risk groups are discussed in the present review.
Identification of possible risk groups for the use of high quercetin doses in dietary supplement.
Although the flavonol quercetin is intensively investigated, our knowledge about its bioavailability and possible target organs is far from being complete. The aim of this study was to check the ...potential of quercetin to accumulate in various tissues after long-term dietary treatment compared with a single treatment with flavonol. Pigs ingested either a single dose of quercetin aglycone (25 mg/kg body weight; Expt. 1) or received the flavonol twice a day at the same dose mixed into their regular meals (i.e 50 mg·kg⁻¹·d⁻¹) for 4 wk (Expt. 2). In both experiments, we took plasma and tissue samples 90 min after the final meal and analyzed them using HPLC. Additionally, the specific activity of the enzyme β-glucuronidase was measured in selected tissues. Higher flavonol concentrations than in plasma were found in only the liver (Expt. 1) or the intestinal wall and kidneys (Expt. 2). All tissues except blood plasma contained a variable amount of deconjugated quercetin in the range of 30-100% of total flavonols. However, the specific β-glucuronidase activity was not correlated with the proportions of deconjugated flavonols in the various tissues. Long-term dietary intake of the flavonol did not lead to a greater accumulation in any tissue compared with the single treatment. Flavonol concentrations only exceeded the plasma concentration within organs involved in its metabolism and excretion, including liver, small intestine, and kidneys.
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.
•Antioxidant and anti-inflammatory activities of quercetin derivatives were studied.•Quercetin metabolites present in systemic circulation have potent biopotential.•Derivatization quercetin resulted ...in decrease of antioxidant activity.•Derivatization of quercetin does not significantly defines anti-inflammatory potential.•Metabolites should be included in defining biopotential of quercetin-rich diet.
Quercetin is hardly bioavailable and largely transformed to different metabolites. Although little is known about their biological activities, these metabolites are crucial for explanation of health benefits associated with quercetin dietary intake. In this study, the antioxidant and anti-inflammatory activities of six quercetin derivatives (quercetin-3-O-glucuronide, tamarixetin, isorhamnetin, isorhamnetin-3-O-glucoside, quercetin-3,4′-di-O-glucoside, quercetin-3,5,7,3′,4′-pentamethylether) were compared with the activity of common onion extract as the main source of dietary quercetin and standards (butylated hydroxytoluene and aspirin). The quercetin derivatives demonstrated notable bioactivities, similar to standards and onion. Derivatization of quercetin hydroxyl groups resulted in decrease of antioxidant potency. However, the number of quercetin free hydroxyl groups was not in direct correlation with its potential to inhibit inflammatory mediators production. To conclude, quercetin derivatives present in systemic circulation after consumption of quercetin may act as potent antioxidant and anti-inflammatory agents and can contribute to overall biological activity of quercetin-rich diet.
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