morin and myricetin

Quercetin oxidation leads to the formation of a metabolite, 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone, whose antioxidant potency was recently reported to be a 1000-fold higher than that of its precursor. The formation of similar metabolites (BZF) is limited to certain flavonols (FL), among which are myricetin, fisetin, and morin. Here we addressed the consequences of inducing the auto-oxidation of these flavonols in terms of their antioxidant properties (assessed in ROS-exposed Caco-2 cells). The mixtures that result from their oxidation (FLox) exhibited antioxidant activities 10-to-50-fold higher than those of their precursors. Such amplification was fully attributable to the presence of BZF in each FLox (established by HPLC-ESI-MS/MS and chemical subtraction techniques). An identical amplification was also found when the antioxidant activities of BZF, isolated from each FLox, and FL were compared. These findings warrant the search of these BZF in edible plants and their subsequent evaluation as a new type of functional food ingredients.

Topics: Antioxidants; Caco-2 Cells; Flavonoids; Flavonols; Humans; Quercetin; Tandem Mass Spectrometry

Flavonoids are a class of polyphenols that possess diverse properties. The structure-activity relationship of certain flavonoids and resveratrol with ribonuclease A (RNase A) has been investigated. The selected flavonoids have a similar skeleton and the positional preferences of the phenolic moieties toward inhibition of the catalytic activity of RNase A have been studied. The results obtained for RNase A inhibition by flavonoids suggest that the planarity of the molecules is necessary for effective inhibitory potency. Agarose gel electrophoresis and precipitation assay experiments along with kinetic studies reveal K

Topics: Animals; Catalytic Domain; Cattle; Enzyme Inhibitors; Flavanones; Flavonoids; Flavonols; Kaempferols; Kinetics; Models, Molecular; Pancreas; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein Structure, Tertiary; Quercetin; Resveratrol; Ribonuclease, Pancreatic; Substrate Specificity; Thermodynamics

The beneficial effects of polyphenols, predominantly in the context of oxidative stress-related diseases such as cancer, cardiovascular diseases and neurological conditions including Alzheimer's and Parkinson's diseases, have been documented by a number of papers and reviews. The antioxidant/prooxidant properties of phenolic compounds are related mainly to the number and positions of hydroxyl groups and to their redox metal (Cu, Fe) chelating capacity. In this work we studied structurally distinct phenolic molecules such as myricetin, morin, 3',4'-dihydroxy-flavone, taxifolin and 4-hydroxycoumarin, either alone or as interacting with Cu

Topics: Antineoplastic Agents; Antioxidants; Chelating Agents; Copper; Coumarins; DNA Damage; Electron Spin Resonance Spectroscopy; Flavonoids; Humans; Hydroxyl Radical; Ions; Photoelectron Spectroscopy; Polyphenols; Quercetin; Reactive Oxygen Species

It has been reported that quercetin is an activator of rat vitamin D receptor (rVDR). However, the conclusion was based on experiments performed without all the appropriate control groups, raising the possibility of a false-positive finding. Furthermore, distinct differences exist in the chemical structures of quercetin and 1α,25-dihydroxyvitamin D3, which is a prototypic agonist of VDR. Therefore, we investigated systematically whether quercetin and other flavonols are agonists of rVDR, mouse VDR (mVDR), or human VDR (hVDR). Quercetin, 3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and syringetin did not activate rVDR, mVDR, or hVDR in HEK-293 and HepG2 cells transfected with the corresponding receptor expression plasmid and either the secreted phosphoprotein 1 (Spp1) or cytochrome P450 24A1 (CYP24A1) reporter plasmid, when compared to the respective empty vector control group transfected with one or the other reporter plasmid and treated with one of the flavonols. Control analysis indicated that lithocholic acid and 1α,25-dihydroxyvitamin D3, but not rifampicin, activated rVDR, mVDR, and hVDR. As shown in transfected HEK293 and HepG2 cells, the flavonols did not influence hVDR ligand binding domain transactivation, steroid receptor coactivator-1 recruitment, or hVDR target gene expression (transient receptor potential cation channel 6 and CYP24A1) in hVDR-expressing Caco-2 or LS180 cells. The cumulative data from the cell-based experiments were corroborated by results obtained from molecular docking analysis. In conclusion, quercetin, 3-hydroxyflavone, galangin, datiscetin, kaempferol, morin, isorhamnetin, tamarixetin, myricetin, and syringetin are not agonists of rVDR, mVDR, or hVDR, as judged by cell-based and in silico evidence.

Topics: Animals; Caco-2 Cells; Calcitriol; Disaccharides; Flavonoids; Gene Expression Regulation; HEK293 Cells; Hep G2 Cells; Humans; Kaempferols; Mice; Molecular Docking Simulation; Osteopontin; Quercetin; Receptors, Calcitriol; Structure-Activity Relationship; Transgenes; Vitamin D3 24-Hydroxylase

The objectives of this study were to identify the antioxidants and antioxidant axtivity in 27 of Taiwan's indigenous vegetables. Lycium chinense (Lc), Lactuca indica (Li), and Perilla ocymoides (Po) contained abundant quercetin (Que), while Artemisia lactiflora (Al) and Gynura bicolor (Gb) were rich in morin and kaempferol, respectively. Additionally, Nymphoides cristata (Nc) and Sechium edule (Se)-yellow had significantly higher levels of myricetin (Myr) than other tested samples. Cyanidin (Cyan) and malvidin (Mal) were abundant in Gb, Abelmoschus esculentus Moench (Abe), Po, Anisogonium esculentum (Retz.) Presl (Ane), Ipomoea batatas (Ib)-purple, and Hemerocallis fulva (Hf)-bright orange. Relatively high levels of Trolox equivalent antioxidant capacity (TEAC), oxygen radical absorption capacity (ORAC), and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenger were generated from extracts of Toona sinensis (Ts) and Po. Significant and positive correlations between antioxidant activity and polyphenols, anthocyanidins, Que, Myr, and morin were observed, indicating that these phytochemicals were some of the main components responsible for the antioxidant activity of tested plants. The much higher antioxidant activity of Po, Ts, and Ib (purple leaf) may be related to their higher Cyan, Que, and polyphenol content.

Topics: Anthocyanins; Antioxidants; Chromatography, High Pressure Liquid; Flavonoids; Kaempferols; Plant Extracts; Plant Leaves; Polyphenols; Reactive Oxygen Species; Taiwan; Vegetables

The microsomal NADH-dependent electron transport system consisting of cytochrome b5 reductase and cytochrome b5 participates in a number of physiologically important processes including lipid metabolism as well as is involved in the metabolism of various drug and xenobiotics. In the present study, we assessed the inhibitory effects of eight dietary flavonoids representing five distinct chemical classes on cytochrome b5 reduction by purified cytochrome b5 reductase. From the flavonoids tested, myricetin was the most potent in inhibiting cytochrome b5 reduction with an IC50 value of 0.35μM. Myricetin inhibited b5 reductase noncompetitively with a Ki of 0.21μM with respect to cofactor NADH, and exhibited a non-linear relationship indicating non-Michaelis-Menten kinetic binding with respect to cytochrome b5. In contrast to the potent inhibitory activity of myricetin, (+)-taxifolin was found to be a weak inhibitor (IC50=9.8μM). The remaining flavonoids were inactive within the concentration range tested (1-50μM). Analysis of structure-activity data suggested that simultaneous presence of three OH groups in ring B is a primary structural determinant for a potent enzyme inhibition. Our results suggest that inhibition of the activity of this system by myricetin or myricetin containing diets may influence the metabolism of therapeutic drugs as well as detoxification of xenobiotics.

Topics: Animals; Apigenin; Catechin; Cattle; Cytochrome-B(5) Reductase; Cytochromes b5; Flavanones; Flavonoids; Microsomes, Liver; Protein Binding; Quercetin; Rabbits

The polypeptide hormone Islet Amyloid Polypeptide (IAPP, amylin) is responsible for islet amyloid formation in type-2 diabetes and in islet cell transplants, where it may contribute to graft failure. Human IAPP is extremely amyloidogenic and fewer inhibitors of IAPP amyloid formation have been reported than for the Alzheimer's Aβ peptide or for α-synuclein. The ability of a set of hydroxyflavones to inhibit IAPP amyloid formation was tested. Fluorescence detected thioflavin-T-binding assays are the most popular methods for measuring the kinetics of amyloid formation and for screening potential inhibitors; however, we show that they can lead to false positives with hydroxyflavones. Several of the compounds inhibit thioflavin-T fluorescence, but not amyloid formation; a result which highlights the hazards of relying solely on thioflavin-T assays to screen potential inhibitors. Transmission electron microscopy (TEM) and right-angle light scattering show that Morin hydrate (2',3,4',5,7-Pentahydroxyflavone) inhibits amyloid formation by human IAPP and disaggregates preformed IAPP amyloid fibers. In contrast, Myricetin, Kaempferol, and Quercetin, which differ only in hydroxyl groups on the B-ring, are not effective inhibitors. Morin hydrate represents a new type of IAPP amyloid inhibitor and the results with the other compounds highlight the importance of the substitution pattern on the B-ring.

Topics: Amyloid; Benzothiazoles; Flavonoids; Humans; Islet Amyloid Polypeptide; Kaempferols; Light; Microscopy, Electron, Transmission; Quercetin; Scattering, Radiation; Thiazoles

Dietary flavonoid intake has been reported to be inversely associated with the incidence of coronary artery disease. To clarify the possible role of flavonoids in the prevention of atherosclerosis, we investigated the effects of some of these compounds, including fisetin, morin and myricetin, on the susceptibility of low-density lipoprotein (LDL) to oxidative modification and on oxLDL uptake in macrophages. The results demonstrated that fisetin had stronger inhibitory activity than the other two on inhibiting Cu(2+)-mediated LDL oxidation measured by thiobarbituric acid-reactive substances assay (TBARS), conjugated diene formation and electrophoretic mobility. The class B scavenger receptor, CD36, to which oxLDL binds, is present in atherosclerotic lesions. Treatment of U937-derived macrophages with myricetin (20 microM) significantly inhibited CD36 cell surface protein and mRNA expression (p<0.01). Fisetin, morin and myricetin (20 microM) also reduced the feed-forward induction of CD36 mRNA and surface protein expression by PPARgamma. The inhibition of CD36 by flavonols was mediated by interference with PPARgamma activation thus counteracting the deleterious autoamplification loop of CD36 expression stimulated by PPARgamma ligand. All three flavonols (10 and 20 microM) markedly decreased the uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanide perchlorate (DiI)-labeled oxLDL uptake in U937-derived macrophages dose-dependently. Current evidences indicate that fisetin, morin and myricetin not only prevent LDL from oxidation but also block oxLDL uptake by macrophages at least in part through reducing CD36 gene expression on macrophages. In conclusion, flavonols may play a role in ameliorating atherosclerosis.

Topics: Anilides; Antioxidants; Blotting, Western; CD36 Antigens; Copper; Endocytosis; Flavonoids; Flavonols; Gene Expression; Humans; Lipoproteins, LDL; Macrophages; Molecular Structure; PPAR gamma; Prostaglandin D2; Reverse Transcriptase Polymerase Chain Reaction; Scavenger Receptors, Class A; Static Electricity; Tetradecanoylphorbol Acetate; Thiobarbituric Acid Reactive Substances; U937 Cells

Generation and accumulation of the amyloid beta peptide (Abeta) following proteolytic processing of the amyloid precursor protein (APP) by BACE-1 (Beta-site APP Cleaving Enzyme-1, beta-secretase) and gamma-secretase is a main causal factor of Alzheimer's disease (AD). Consequently, inhibition of BACE-1, a rate-limiting enzyme in the production of Abeta, is an attractive therapeutic approach for the treatment of AD. In this study, we discovered that natural flavonoids act as non-peptidic BACE-1 inhibitors and potently inhibit BACE-1 activity and reduce the level of secreted Abeta in primary cortical neurons. In addition, we demonstrated the calculated docking poses of flavonoids to BACE-1 and revealed the interactions of flavonoids with the BACE-1 catalytic center. We firstly revealed novel pharmacophore features of flavonoids by using cell-free, cell-based and in silico docking studies. These results contribute to the development of new BACE-1 inhibitors for the treatment of AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Apigenin; Aspartic Acid Endopeptidases; Catalytic Domain; Cell Survival; Cerebral Cortex; Flavones; Flavonoids; Flavonols; Humans; Hydrogen Bonding; Kaempferols; Models, Molecular; Molecular Structure; Neurons; Protease Inhibitors; Quercetin; Rats; Structure-Activity Relationship

The non-enzymatic glycation of Low density lipoprotein (LDL) is a naturally occurring chemical modification of apolipoprotein B as a result of condensation between lysine residues and glucose. Glycated LDL is poorly recognized by LDL receptors and initiates different processes that can be considered proatherogenic. Thus, LDL glycation may contribute in the increased atherosclerotic risk of patients with diabetes. The objective of this study was to investigate the effect of naturally occurring flavonols on LDL glycation in vitro.. In this study, LDL was isolated from EDTA-plasma by ultracentrifugation using a single step discontinuous gradient. Then, glucose was added to LDL and LDL glycation level was estimated in absence and presence of flavonols by sodium periodate assay.. This study was showed that five flavonols: quercetin, myricetin, kaempferol, rutin and morin decreased LDL glycation in a dose-dependent manner. Also, it was demonstrated this nutrients decreased electrophoretic mobility of glycated LDL.. The results of this investigation show that flavonols probably with their antioxidant properties inhibited LDL glycation and thus may have a role in ameliorating atherosclerotic risk of patients with diabetes mellitus.

Topics: Adult; Antioxidants; Atherosclerosis; Diabetic Angiopathies; Flavonoids; Flavonols; Glycation End Products, Advanced; Glycosylation; Humans; In Vitro Techniques; Kaempferols; Lipoproteins, LDL; Male; Quercetin; Rutin

Cerebral deposition of amyloid beta-peptide (Abeta) in the brain is an invariant feature of Alzheimer's disease (AD). A consistent protective effect of wine consumption on AD has been documented by epidemiological studies. In the present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of wine-related polyphenols (myricetin, morin, quercetin, kaempferol (+)-catechin and (-)-epicatechin) on the formation, extension, and destabilization of beta-amyloid fibrils (fAbeta) at pH 7.5 at 37 degrees C in vitro. All examined polyphenols dose-dependently inhibited formation of fAbeta from fresh Abeta(1-40) and Abeta(1-42), as well as their extension. Moreover, these polyphenols dose-dependently destabilized preformed fAbetas. The overall activity of the molecules examined was in the order of: myricetin = morin = quercetin > kaempferol > (+)-catechin = (-)-epicatechin. The effective concentrations (EC50) of myricetin, morin and quercetin for the formation, extension and destabilization of fAbetas were in the order of 0.1-1 micro m. In cell culture experiments, myricetin-treated fAbeta were suggested to be less toxic than intact fAbeta, as demonstrated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Although the mechanisms by which these polyphenols inhibit fAbeta formation from Abeta, and destabilize pre-formed fAbetain vitro are still unclear, polyphenols could be a key molecule for the development of preventives and therapeutics for AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Benzothiazoles; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Flavonoids; Humans; Kidney; Kinetics; Microscopy, Electron; Peptide Fragments; Phenols; Polymers; Quercetin; Spectrometry, Fluorescence; Tetrazolium Salts; Thiazoles

Mast cells are involved in allergic and inflammatory reactions. These cells are also increased in the bone marrow, skin, and other organs in systemic mastocytosis. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory activities. Some flavonoids, like quercetin, inhibit the growth of certain malignant cells in culture. Quercetin also inhibits histamine release and induces accumulation of secretory granules in rat basophilic leukemia cells.. We investigated the effect of five flavonoids: flavone, kaempferol, morin, myricetin, and quercetin at 1, 10, and 100 microM on proliferation and secretory mediator content (beta-hexosaminidase, histamine, and tryptase) in human leukemic mast cells (HMC-1), the doubling time of which was about 2 d.. Flavone and kaempferol at 100 microM inhibited cell proliferation over 80% on either day 3, 4, or 5 of culture. Quercetin showed this level of inhibition only on day 5, myricetin inhibited by 50% at days 3-5, whereas morin's inhibition was < 20%. All flavonoids (except morin) at 100 microm increased histamine and tryptase content, but not beta-hexosaminidase, equally at days 3 and 4 of culture quercetin also increased the development of secretory granules.. These results indicate that certain flavonoids can inhibit HMC-1 proliferation, induce secretory granule development and the accumulation of mediators.

Topics: beta-N-Acetylhexosaminidases; Cell Division; Cell Survival; Flavones; Flavonoids; Histamine; Humans; Kaempferols; Leukemia, Mast-Cell; Mast Cells; Microscopy, Electron; Quercetin; Secretory Vesicles; Serine Endopeptidases; Tryptases; Tumor Cells, Cultured

Topics: Blood Platelets; Catechin; Collagen; Diet; Flavonoids; Humans; In Vitro Techniques; Platelet Aggregation; Platelet Aggregation Inhibitors; Quercetin; Thrombin

Low density lipoproteins (LDL) can be oxidatively modified in vitro by macrophages and certain other cell types so that macrophages will take them up much faster. This process may be important in the formation of cholesterol-laden foam cells derived from macrophages in atherosclerotic lesions. In this study, we have shown that certain flavonoids, plant constituents found in the diet, are potent inhibitors of the modification of 125I-labelled LDL by macrophages, with IC50 values in the micromolar range (e.g. morin and fisetin 1 microM; quercetin and gossypetin 2 microM). The potencies of individual flavonoids in inhibiting LDL modification did not correlate with their previously determined potencies as inhibitors of 5-lipoxygenase and cyclo-oxygenase. The modification of LDL by macrophages exhibits a lag period of about 4-6 hr before enhanced uptake is detected. During this time, there is a rapid depletion in its content of alpha-tocopherol (an endogenous antioxidant found in lipoproteins) followed by a large increase in the level of hydroperoxides. The flavonoids conserved the alpha-tocopherol content of LDL and delayed the onset of detectable lipid peroxidation. Flavonoids also inhibited the cell-free oxidation of LDL mediated by CuSO4. These findings raise the possibility that flavonoids may protect LDL against oxidation in atherosclerotic lesions and may therefore be natural anti-atherosclerotic components of the diet, although this will depend to a large extent on their pharmacokinetics.

Topics: Copper; Flavonoids; Humans; Lipoproteins, LDL; Macrophages; Oxidation-Reduction; Quercetin; Time Factors

The ability of 3 plant flavonoids (morin, myricetin and quercetin) and 4 polyphenolic acids (caffeic acid, chlorogenic acid, ellagic acid and ferulic acid) to inhibit the genotoxic effects of a number of cooked-food mutagens (IQ, MeIQ, MeIQx, Trp-P-1 and Trp-P-2), was investigated in a bacterial mutation assay using Salmonella typhimurium TA98 as indicator and hepatic S9 mixes from either SWR mice or Syrian hamsters as metabolic activating systems. Although the polyphenolic acids failed to have an effect, the flavonoids generally inhibited IQ, MeIQ, MeIQx and Trp-P-1 induced mutagenesis in a dose-dependent manner, irrespective of the source of S9. This was not the case with Trp-P-2 where the flavonoids were only observed to inhibit when SWR mouse S9 but not Syrian hamster S9 was used. Of the 3 compounds, myricetin and quercetin were superior to morin in their inhibitory capacity.

Topics: Animals; Benzopyrans; Biotransformation; Caffeic Acids; Chlorogenic Acid; Cinnamates; Coumaric Acids; Cricetinae; Drug Interactions; Ellagic Acid; Flavonoids; Food Handling; Male; Mesocricetus; Mice; Mice, Inbred Strains; Mutagens; Mutation; Quercetin; Salmonella typhimurium