myricitrin and myricetin

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta and decreases in striatal dopamine levels. These changes led to several clinical symptoms: rigidity, resting tremor, and bradykinesia. Although the cause of PD remains unclear, it is widely accepted that oxidative stress, neuroinflammation, mitochondrial dysfunction, and insufficient support of neurotrophic factors are involved in the pathophysiology of the disease. However, novel regimens to prevent neurodegeneration and restore the degenerated nigrostriatal DA system are still required. In recent years, there has been a growing interest in naturally occurring phytochemicals, which are believed to reduce the risk of neurodegenerative diseases. This review provides an overview of the scientific literature concerning the preventive and protective roles of flavonoids, one of the largest families of phytochemicals, against PD. In addition to providing antioxidant and anti-inflammatory effects, flavonoids exhibit a neuroprotective effect by activating antiapoptotic pathways that target mitochondrial dysfunction and induce neurotrophic factors. This review suggests that flavonoids may be promising natural products for the prevention of PD and could potentially be utilized as therapeutic compounds against PD, even though there was no report showing that the treatment with flavonoids could restore the aberrant phenotypes of patients with PD.

Topics: Animals; Anthocyanins; Antioxidants; Antiparkinson Agents; Catechin; Cell Line; Corpus Striatum; Disease Models, Animal; Dopamine; Flavanones; Flavones; Flavonoids; Flavonols; Humans; Isoflavones; Kaempferols; Neuroprotective Agents; Oxidative Stress; Parkinson Disease

Myricetin (MYR) and myricitrin (MYT) are well recognized for their nutraceutical value, such as antioxidant, hypoglycemic, and hypotensive effects. In this work, fluorescence spectroscopy and molecular modeling were adopted to investigate the conformational and stability changes of proteinase K (PK) in the presence of MYR and MYT. The experimental results showed that both MYR and MYT could quench fluorescence emission via a static quenching mechanism. Further investigation demonstrated that both hydrogen bonding and van der Waals forces play significant roles in the binding of complexes, which is consistent with the conclusions of molecular modeling. Synchronous fluorescence spectroscopy, Förster resonance energy transfer, and site-tagged competition experiments were performed to prove that the binding of MYR or MYT to PK could alter its micro-environment and conformation. Molecular docking results revealed that either MYR or MYT spontaneously interacted with PK at a single binding site via hydrogen bonding and hydrophobic interactions, which is consistent with the results of spectroscopic measurements. A 30 ns molecular dynamics simulation was conducted for both PK-MYR and PK-MYT complexes. The calculation results showed that no large structural distortions or interaction changes occurred during the entire simulation time span. The average RMSD changes of PK in PK-MYR and PK-MYT were 2.06 and 2.15 Å, respectively, indicating excellent stability of both complexes. The molecular simulation results suggested that both MYR and MYT could interact with PK spontaneously, which is in agreement with spectroscopic results. This agreement between experimental and theoretical results indicates that the method herein could be feasible and worthwhile for protein-ligand complex studies.

Topics: Binding Sites; Endopeptidase K; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Binding; Spectrometry, Fluorescence; Thermodynamics

African swine fever (ASF) caused by the ASF virus (ASFV) is the most hazardous swine disease. Since a huge number of pigs have been slaughtered to avoid a pandemic spread, intense studies on the disease should be followed quickly. Recent studies reported that flavonoids have various antiviral activity including ASFV. In this report, ASFV protease was selected as an antiviral target protein to cope with ASF. With a FRET (Fluorescence resonance energy transfer) method, ASFV protease was assayed with a flavonoid library which was composed of sixty-five derivatives classified based on ten different scaffolds. Of these, the flavonols scaffold contains a potential anti-ASFV protease activity. The most prominent flavonol was myricetin with IC

Topics: African Swine Fever Virus; Antiviral Agents; Dose-Response Relationship, Drug; Endopeptidases; Flavonoids; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Viral Proteins

Phytochemical investigation of the methanolic extract of dried leaves of Bridelia ferruginea led to the isolation and identification of fourteen compounds (1-14): compound 1 [mixture of palmitic, stearic and oleic acids], stearyl monoester of 2-O-β-ᴅ-glucosylglycerol (2), 6β-hydroxy-(20R)-24-ethylcholest-4-en-3-one (3a), 6β-hydroxy-(20R)-24-ethylcholest-4,22-dien-3-one (3b), lutein (4), vomifoliol (5), corilagin (6), kaempferide-3-O-β-ᴅ-glucoside (7), myricetin (8), isomericitrin (9), isoquercetin (10), myricitrin (11), quercitrin (12), rutin (13), and β-sitosterol glucoside (14). The total extract exhibited moderate activity towards CB2 receptor and 90% inhibition against leishmanial pathogen Trypanosoma brucei. Compound 4 exhibited 73% displacement in CB2 receptor with IC

Topics: Escherichia coli; Euphorbiaceae; Flavonoids; Glucosides; Hydrolyzable Tannins; Nigeria; Phytochemicals; Plant Extracts; Plant Leaves; Receptor, Cannabinoid, CB2; Trypanosoma brucei brucei

Bioassay-guided fractionation of the methanol extract of the shoots of Myrsine africana led to the isolation of the new compound myricetin 3-O-(2″,4″-di-O-acetyl)-α-l-rhamnopyranoside (9) and 11 known compounds. The known compounds quercetin 3-O-(3″,4″-di-O-acetyl)-α-l-rhamnopyranoside (8), rutin (10), quercetin 3-O-α-l-rhamnopyranoside (11), and myricetin 3-O-α-l-rhamnopyranoside (12) are reported for the first time from the methanol extract of the shoots of M. africana. Compounds 10 and 12 showed significant inhibition of tyrosinase with 50% inhibition (IC

Topics: Agaricales; Antioxidants; Flavonoids; Glycosides; Molecular Docking Simulation; Myrsine; Plant Extracts; Quercetin

The gastrointestinal (GI) stability of three flavonoids, dihydromyricetin (DMY), myricetin (MYR), and myricitrin (MYT), was examined in simulated physiological fluids. Several factors that may influence the degradation rate of theses flavonoids were evaluated, including pH and the presence of pepsin and pancreatin enzymes. We found that GI stability followed the order of MYT > DMY > MYR. These flavonoids were stable in simulated gastric fluids and buffer solutions (pH 1.2), but encountered a pseudo-first-order kinetic degradation in simulated intestinal fluids and buffer solutions (pH 6.8). We conclude that it is the pH, rather than the presence of pepsin or pancreatin, which most strongly influences the stability of these three flavonoids. Further study of the stability of the compounds using a pH range (1.0-8.0) indicated potential instability in the duodenum, small intestine, and colon. Therefore, we conclude that the low bioavailability of these flavonoids may be due to their poor stability in the GI tract.

Topics: Biological Availability; Flavonoids; Flavonols; Gastrointestinal Tract; Humans; Hydrogen-Ion Concentration; Limit of Detection; Pancreatin; Pepsin A; Reproducibility of Results

The fermented leaf of Ampelopsis grossedentata has been used as a beverage and folk medicine called "vine tea" in the southern region of China. In this paper, the optimum extraction conditions for the maximum recovery amounts of total flavonoids (TF), dihydromyricetin (DMY), myricitrin (MYG) and myricetin (MY) from natural Ampelopsis grossedentata leaves subjected to ultrasonic-assisted extraction (UAE) were determined and optimized by using response surface methodology. The method was employed by the Box-Behnken design (BBD) and Derringer's desirability function using methanol concentration, extraction time, liquid/solid ratio as factors and the contents of TF, DMY, MYG and MY as responses. The obtained optimum UAE conditions were as follows: a solvent of 80.87% methanol, an extraction time of 31.98 min and a liquid/solid ratio of 41.64:1 mL/g. Through analysis of the response surface, it implied that methanol concentration and the liquid/solid ratio had significant effects on TF, DMY, MYG and MY yields, whereas extraction time had relatively little effects. The established extraction and analytical methods were successfully applied to determine the contents of the total flavonoids and three individual flavonoids in 10 batches of the leaf samples of A. grossedentata from three counties in Fujian Province, China. The results suggested the variability in the quality of A. grossedentata leaves from different origins. In addition, high purities of dihydromyricetin and myricetin were simultaneously separated and purified from the extract subjected to optimized UAE, by high-speed counter-current chromatography using a solvent system of N-hexane-ethyl acetate-methanol-water (1:3:2:4; v/v/v/v). In a single operation, 200 mg of the extract were separated to yield 86.46 mg of dihydromyricetin and 3.61 mg of myricetin with the purity of 95.03% and 99.21%, respectively. The results would be beneficial for further exploiting the herbal products and controlling the quality of the herb and its derived products.

Topics: Ampelopsis; Chromatography, Liquid; Countercurrent Distribution; Flavonoids; Flavonols; Molecular Structure; Plant Extracts; Plant Leaves; Ultrasonics

Myricitrin, a flavonoid extracted from the fruit, leaves, and bark of Chinese bayberry (Myrica rubra SIEBOLD), is currently used as a flavor modifier in snack foods, dairy products, and beverages in Japan. Myricitrin is converted to myricetin by intestinal microflora; myricetin also occurs ubiquitously in plants and is consumed in fruits, vegetables, and beverages. The genotoxic potential of myricitrin and myricetin was evaluated in anticipation of worldwide marketing of food products containing myricitrin. In a bacterial reverse mutation assay, myricetin tested positive for frameshift mutations under metabolic activation conditions whereas myricitrin tested negative for mutagenic potential. Both myricitrin and myricetin induced micronuclei formation in human TK6 lymphoblastoid cells under conditions lacking metabolic activation; however, the negative response observed in the presence of metabolic activation suggests that rat liver S9 homogenate may detoxify reactive metabolites of these chemicals in mammalian cells. In 3-day combined micronucleus/Comet assays using male and female B6C3F1 mice, no induction of micronuclei was observed in peripheral blood, or conclusive evidence of damage detected in the liver, glandular stomach, or duodenum following exposure to myricitrin or myricetin. Our studies did not reveal evidence of genotoxic potential of myricitrin in vivo, supporting its safe use in food and beverages.

Topics: Animals; DNA Damage; Female; Flavonoids; Food Additives; Fruit; Glycosides; Humans; Japan; Male; Mice; Mutagenicity Tests; Myrica; Plant Bark; Plant Leaves; Rats; Toxicity Tests, Acute

Catechol O-methyltransferase (COMT) is an important enzyme involved in the metabolism of levodopa (L-dopa) which is clinically used to treat Parkinson's disease through boosting the concentration of dopamine in the brain. Development of COMT inhibitors can efficiently increase the bioavailability of L-dopa. The present study aims to evaluate the inhibition of COMT activity by three herbal components isolated from Myrica rubra Sieb. et Zucc.. The in vitro human liver cytosol-catalyzed L-dopa methylation reaction was utilized. The results showed that all these three compounds strongly inhibited COMT activity in a concentration-dependent manner. The inhibition was competitive for these three compounds, as demonstrated by Dixon and Lineweaver-Burk plots. The inhibition kinetic parameters (Ki) towards COMT activity were calculated to be 0.5, 0.2, and 0.9 microM for myricitrin, myricetin, and dihydromyricetin, respectively. From the view of structures, the deglycosylation biotransformation of myricitrin into myricetin can increase the inhibitory ability towards COMT. However, further structural alteration of myricetin towards dihydromyricetin weakens the inhibitory potential towards COMT.

Topics: Catechol O-Methyltransferase Inhibitors; Cytosol; Dose-Response Relationship, Drug; Enzyme Inhibitors; Flavonoids; Flavonols; Humans; Indicators and Reagents; Kinetics; Levodopa; Liver; Methylation; Structure-Activity Relationship

To investigate the metabolic routes and metabolites of myricitrin, an important active ingredient of traditional herbal medicine, yielded by the isolated human intestinal bacteria, which have not been reported previously.. Fresh human fecal samples were collected from a healthy female volunteer and about 100 different bacterial colonies were isolated. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry technique combined with Metabolynx™ software was used for analysis of the metabolic profile of myricitrin by the isolated human intestinal bacteria.. One hundred different bacterial colonies, which developed on plates, were picked up, and four of them were further identified by using the technique of 16S rRNA gene sequencing due to their relatively strong metabolic capacity toward myricitrin. Most of them belong to Escherichia. Parent compound and three metabolites (quercetin-3-O-rhamnoside, myricetin and quercetin) were detected in the isolated bacterial samples compared with blank samples. The metabolic pathways of myricitrin included deglycosylation and dehydroxylation.. These metabolites suggested that myricitrin was first dehydroxylated to quercetin-3-O-rhamnoside and subsequently deglycosylated to quercetin. Additionally, myricitrin could also be deglycosylated to the aglycon myricetin. Moreover, those metabolites might influence the biological effect of myricitrin in vivo, which led to affect the clinical effects of the medicinal plants and traditional herb medicines.

Topics: Adult; Chromatography, High Pressure Liquid; Feces; Female; Flavonoids; Humans; In Vitro Techniques; Intestines; Mass Spectrometry; Quercetin; RNA, Ribosomal, 16S

Target-based drug discovery for Alzheimer's disease (AD) centered on modulation of the amyloid β peptide has met with limited success. Therefore, recent efforts have focused on targeting the microtubule-associated protein tau. Tau pathologically accumulates in more than 15 neurodegenerative diseases and is most closely linked with postsymptomatic progression in AD. We endeavored to identify compounds that decrease tau stability rather than prevent its aggregation. An extract from Myrica cerifera (bayberry/southern wax myrtle) potently reduced both endogenous and overexpressed tau protein levels in cells and murine brain slices. The bayberry flavonoids myricetin and myricitrin were confirmed to contribute to this potency, but a diarylheptanoid, myricanol, was the most effective anti-tau component in the extract, with potency approaching the best targeted lead therapies. (+)-aR,11S-Myricanol, isolated from M. cerifera and reported here for the first time as the naturally occurring aglycone, was significantly more potent than commercially available (±)-myricanol. Myricanol may represent a novel scaffold for drug development efforts targeting tau turnover in AD.

Topics: Alzheimer Disease; Animals; Diarylheptanoids; Female; Flavonoids; HeLa Cells; Humans; Male; Mice; Models, Biological; Myrica; Plant Roots; Prosencephalon; tau Proteins

Davilla nitida and Davilla elliptica (Dilleniaceae) are plants that occur predominantly in the cerrado region of South America. They are used in popular medicine to treat stomach diseases, diarrhea and swelling, particularly of the lymph nodes and testicles. Chemical investigation of these two plant species led to the identification of the compounds myricetin-3-O-α-l-rhamnoside (myricitrin), quercetin-3-O-α-l-rhamnoside (quercitrin), myricetin, quercetin and gallic acid derivatives in the leaves of D. nitida and D. elliptica. Therefore, it was concluded that the two species of Davilla possess qualitatively similar chemical profiles. In the present study, the mutagenic and genotoxic potential of these plants and of their isolated compounds was tested in the Salmonella typhimurium assay (Ames test) with strains TA100, TA98, TA102 and TA97a, in the micronucleus test with peripheral blood cells of mice treated in vivo, and in plasmid DNA to analyze DNA strand-breaks. In the assessment of mutagenic potential by the Ames test, extracts from both plant species and a D. nitida ethyl-acetate fraction induced positive responses. On the other hand, none of the extracts showed genotoxic activity in the mouse cells. In the presence of metal ion, D. nitida and D. elliptica aqueous and ethyl-acetate fractions, as well as their isolated compounds, induced single- and double-strand-breaks in plasmid DNA in a cell-free system.

Topics: Animals; Dilleniaceae; DNA Damage; Flavonoids; Gallic Acid; Mice; Micronucleus Tests; Mutagenicity Tests; Mutagens; Plant Extracts; Plant Leaves; Plasmids; Quercetin; Salmonella typhimurium

To study the constituents of the leaves of Heliciopsis lobata.. Compounds were isolated by column chromatography on silica gel, neutral aluminum oxide and Sephadex LH -20, and their structures were identified by spectroscopic and physicochemical data.. Seven known compounds were isolated and identified as: myricetin (1), myricitrin (2), syringetin-3-O-beta-D-glucopyranoside (3), medioresinol (4), D-1-O-methyl-myo-inositol (5), hydroquinone (6), and beta-sitosterol (7).. All of these compounds were isolated from genus Heliciopsis for the first time.

Topics: Flavonoids; Hydroquinones; Magnetic Resonance Spectroscopy; Plant Leaves; Proteaceae; Sitosterols

Colorectal carcinoma is a leading cause of human mortality due to its high metastatic ability. Because the activation of matrix metalloproteinases (MMP) is a key factor in the metastatic process, agents with the ability to inhibit MMP activity have potential in the treatment of colorectal carcinoma. In the present study, among 36 flavonoids examined, myricetin was found to be the most potent inhibitor of MMP-2 enzyme activity in COLO 205 cells (IC50 = 7.82 micromol/L). Myricetin inhibition of MMP-2 enzyme activity was also found in the human colorectal carcinoma cell lines COLO 320HSR, COLO 320DM, HT 29, and COLO 205-X (IC50 = 11.18, 11.56, 13.25, and 23.51 micromol/L, respectively). In contrast, no inhibitory effect of MMP-2 protein expression or enzyme activity was observed in myricitrin (myricetin-3-rhamnoside)-treated cells. In 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated COLO 205 cells, an increase in MMP-2 protein expression and enzyme activity, as well as of protein kinase C (PKC) alpha protein translocation, extracellular signal-regulated kinase (ERK) 1/2 protein phosphorylation, and c-Jun protein expression was observed. ERK inhibitor (PD98059) and PKC inhibitors (GF-109203X and H-7), but not p38 inhibitor (SB203580) or c-jun-NH2-kinase inhibitor (SP600125), significantly inhibited TPA-induced MMP-2 protein expression, with reduced ERK phosphorylation and c-Jun protein expression. Addition of myricetin but not myricitrin suppressed TPA-induced MMP-2 protein expression in COLO 205 cells by blocking the TPA-induced events, including translocation of PKCalpha from cytosol to membrane, phosphorylation of ERK1/2 protein, and induction of c-Jun protein expression. Addition of PD98059 or GF-109203X significantly enhanced the inhibitory effect of myricetin on MMP-2 enzyme activity induced by TPA. Furthermore, myricetin, but not myricitrin, suppressed TPA-induced invasion of COLO 205 cells in an in vitro invasion assay using Engelbreth-Holm-Swarm sarcoma tumor extract Matrigel-coated Transwells. Results of the present study indicate that myricetin significantly blocked both endogenous and TPA-induced MMP-2 enzyme activity by inhibiting its protein expression and enzyme activity. The blockade involved suppression of PKC translocation, ERK phosphorylation, and c-Jun protein expression.

Topics: Antineoplastic Agents; Carcinoma; Cell Line, Tumor; Colorectal Neoplasms; Enzyme Activation; Flavonoids; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Phosphorylation; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Transport; Tetradecanoylphorbol Acetate

To study the chemical constituents from Ampelopsis grossedentata (hand-Mazz) W.T. Wang.. Chromatography and spectroscopic analysis were employed to isolate and elucidate the chemical constituents in the plant.. Seven compounds were isolated and elucidated as ampelopsin (I), myricetin (II), myricitrin (III), gallic acid (IV), beta-sitosterol (V), stigmasterol (VI) and dihydroquercetin (VII).. Among these compounds, IV, V, VI and VII were isolated from this plant for the first time, and compound VII was obtained from genus Ampelopsis for the first time.

Topics: Ampelopsis; Drugs, Chinese Herbal; Flavonoids; Flavonols; Molecular Structure; Plant Leaves; Plants, Medicinal; Quercetin; Sitosterols; Spectrophotometry, Ultraviolet; Spectroscopy, Near-Infrared; Stigmasterol

Five compounds were isolated from the aerial part of Ampelopsis grossedentata and identified as ampelopsin, ambrein, beta-sitosterol, myricetin and myricitrin by means of UV, IR, 1HNMR and MS spectral analysis. They were isolated from this plant for the first time.

Topics: Drugs, Chinese Herbal; Flavonoids; Magnoliopsida; Molecular Structure; Naphthols; Plants, Medicinal; Sitosterols; Triterpenes