Myricitrin Research Articles

LC-ESI-QTOF-MS for the Profiling of the Metabolites and in Vitro Enzymes Inhibition Activity of Bryophyllum pinnatum and Oxalis corniculata Collected from Ramechhap District of Nepal.

The objective of this study was to profile the chemical components and biological activity analysis of crude extract of Bryophyllum pinnatum and Oxalis corniculata. Results revealed that the analyzed plant materials encompass the high amount of total phenolic and flavonoids content and have significant antioxidant activities. Furthermore, methanol extracts are the potential source of α-amylase, α-glucosidase, lipase, tyrosinase and elastase inhibitors. High resolution mass spectrometry revealed the presence of diverse metabolites such as quercetin 3-O-α-L-rhamnopyranoside, myricetin 3-rhamnoside, bersaldegenin 1,3,5-orthoacetate, bryophyllin C, syringic acid, caffeic acid, p-coumaric acid, and quercetin in B. pinnatum and isoorientin, swertisin, apigenin 7,4'-diglucoside, vitexin, 4-hydroxybenzoic acid, vanillic acid, ethyl gallate, 3,3',4'-trihydroxy-5,7-dimethoxyflavone, and diosmetin-7-O-β-D-glucopyranoside in O. corniculata. Our finding suggested that these two plant species have high medicinal importance and are potential source of inhibitors for modern pharmaceuticals, nutraceuticals and cosmetics industries.

The Structural Integrity of the Model Lipid Membrane during Induced Lipid Peroxidation: The Role of Flavonols in the Inhibition of Lipid Peroxidation.

The structural integrity, elasticity, and fluidity of lipid membranes are critical for cellular activities such as communication between cells, exocytosis, and endocytosis. Unsaturated lipids, the main components of biological membranes, are particularly susceptible to the oxidative attack of reactive oxygen species. The peroxidation of unsaturated lipids, in our case 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), induces the structural reorganization of the membrane. We have employed a multi-technique approach to analyze typical properties of lipid bilayers, i.e., roughness, thickness, elasticity, and fluidity. We compared the alteration of the membrane properties upon initiated lipid peroxidation and examined the ability of flavonols, namely quercetin (QUE), myricetin (MCE), and myricitrin (MCI) at different molar fractions, to inhibit this change. Using Mass Spectrometry (MS) and Fourier Transform Infrared Spectroscopy (FTIR), we identified various carbonyl products and examined the extent of the reaction. From Atomic Force Microscopy (AFM), Force Spectroscopy (FS), Small Angle X-Ray Scattering (SAXS), and Electron Paramagnetic Resonance (EPR) experiments, we concluded that the membranes with inserted flavonols exhibit resistance against the structural changes induced by the oxidative attack, which is a finding with multiple biological implications. Our approach reveals the interplay between the flavonol molecular structure and the crucial membrane properties under oxidative attack and provides insight into the pathophysiology of cellular oxidative injury.

Myricitrin Ameliorates Hyperglycemia, Glucose Intolerance, Hepatic Steatosis, and Inflammation in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic β-cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes—fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-α levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.

Antiepileptogenic effect of myricitrin on spatial memory and learning in a kainate-induced model of temporal lobe epilepsy

Temporal lobe epilepsy (TLE) causes impairment in learning and memory by causing neurological damage. Using the antioxidant and anti-inflammatory effects of myricitrin (MYC), the present study was conducted in order to investigate the neuroprotection effects of MYC in kainic acid (KA) induced- TLE experimental model.Forty male Wistar rats were divided into five groups: 1: Sham, 2: MYC, 3: TLE (epileptic group), 4: VA + TLE (valproic acid and KA recipient), and 5: MYC + TLE (MYC and KA recipient). Intra-hippocampal KA was used for induction of epilepsy. Five mg/kg of MYC was administered from one week before surgery to one hour prior to KA injection intraperitoneally. Shuttle box and Morris water maze tasks were used to investigate passive avoidance and spatial memory respectively. Also, tumor necrosis factor-α (TNF- α) as an inflammatory cytokine, total antioxidant capacity (TAC) and malondialdehyde (MDA) in hippocampal tissue were measured.Intra-hippocampal KA led to the elevation of the severity of seizure scores (SS), hippocampal TNF- α and reduction of TAC concentrations. Administration of MYC attenuated the severity of SS and TNF- α concentrations significantly. The hippocampal TAC concentration increased significantly in the KA + MYC group. Behavioral evaluation also showed that pretreatment with 5 mg/kg of MYC improved the ability to maintain information in passive avoidance and spatial memory tasks.The results of this study indicate that TLE causes neuronal damage of the hippocampus, and pretreatment with MYC prevents KA-induced TLE through its antioxidant and anti-inflammatory activity.

Discovery of UDP-Glycosyltransferases and BAHD-Acyltransferases Involved in the Biosynthesis of the Antidiabetic Plant Metabolite Montbretin A.

Plant specialized metabolism serves as a rich resource of biologically active molecules for drug discovery. The acylated flavonol glycoside montbretin A (MbA) and its precursor myricetin 3-O-(6'-O-caffeoyl)-glucosyl rhamnoside (mini-MbA) are potent inhibitors of human pancreatic α-amylase and are being developed as drug candidates to treat type-2 diabetes. MbA occurs in corms of the ornamental plant montbretia (Crocosmia x crocosmiiflora), but a system for large-scale MbA production is currently unavailable. Biosynthesis of MbA from the flavonol myricetin and MbA accumulation occur during early stages of corm development. We established myricetin 3-O-rhamnoside (MR), myricetin 3-O-glucosyl rhamnoside (MRG), and mini-MbA as the first three intermediates of MbA biosynthesis. Contrasting the transcriptomes of young and old corms revealed differentially expressed UDP-sugar-dependent glycosyltransferases (UGTs) and BAHD-acyltransferases (BAHD-ATs). UGT77B2 and UGT709G2 catalyze the consecutive glycosylation of myricetin to produce MR and of MR to give MRG, respectively. In addition, two BAHD-ATs, CcAT1 and CcAT2, catalyze the acylation of MRG to complete the formation of mini-MbA. Transcript profiles of UGT77B2, UGT709G2, CcAT1, and CcAT2 during corm development matched the metabolite profile of MbA accumulation. Expression of these enzymes in wild tobacco (Nicotiana benthamiana) resulted in the formation of a surrogate mini-MbA, validating the potential for metabolic engineering of mini-MbA in a heterologous plant system.

Optimization of Acid Hydrolysis of Myricetin-3-O-rhamnoside Using Response Surface Methodology

This study aimed to optimize the acid hydrolysis of glycosylated flavonols, to apply the optimum conditions for hydrolyzing Inga edulis extract (IEE), rich in glycosylated flavonols, and evaluating its impact on the antioxidant capacity. To evaluate the influence of three independent variables on the aglycone obtained after the reaction, the response surface methodology was applied using myricetin-3-O-rhamnoside (M3R) as a pure compound. The phenolic compound profile and antioxidant capacity were determined by high-performance liquid chromatography (HPLC) and the Trolox-equivalent antioxidant capacity (TEAC) assay, respectively. The maximum content of the aglycone myricetin (81.15%) occurred with 2.5 M HCl at 75 oC for 60 min. Under these conditions, the IEE produced the aglycones myricetin, quercetin and cyanidin. The TEAC values of the M3R samples and IEE before and after acid hydrolysis did not show significant differences (p > 0.05). These results suggest that the hydrolytic process is effective to produce aglycone flavonoids from leaf extracts of I. edulis, and probably for other plant extracts rich in M3R.

The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity in vitro

BackgroundPlant extracts are sources of valuable compounds with biological activity, especially for the anti-proliferative activity against pathogens or tumor cells. Myricetin is a flavonoid found in several plants that has been described as an inhibitor of Human immunodeficiency virus type 1 (HIV-1) through its action against the HIV reverse transcriptase, but myricetin derivatives have not been fully studied. The aim of this study was to evaluate the anti-HIV-1 activity of glycosylated metabolites obtained from Marcetia taxifolia and derived from myricetin: myricetin rhamnoside and myricetin 3-(6-rhamnosylgalactoside).MethodsCompounds were obtained from organic extracts by maceration of aerial parts of M. taxifolia. All biological assays were performed in the MT4 cell line. Antiviral activity was measured as inhibition of p24 and reverse transcriptase with a fluorescent assay.ResultsBoth flavonoids have antiviral activity in vitro, with an EC50 of 120 µM for myricetin 3-rhamnoside (MR) and 45 µM for myricetin 3-(6-rhamnosylgalactoside) (MRG), both significantly lower than the EC50 of myricetin (230 µM). Although both compounds inhibited the reverse transcriptase activity, with an IC50 of 10.6 µM for MR and 13.8 µM for MRG, myricetin was the most potent, with an IC50 of 7.6 µM, and an inhibition greater than 80%. Molecular docking approach showed correlation between the free energy of binding with the assays of enzyme inhibition.ConclusionsThe results suggest that glycosylated moiety might enhance the anti-HIV-1 activity of myricetin, probably by favoring the internalization of the flavonoid into the cell. The inhibition of the HIV-1 reverse transcriptase is likely responsible for the antiviral activity.

Gastrointestinal stability of dihydromyricetin, myricetin, and myricitrin: an in vitro investigation

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.

ANTI-CANCER ACTIVITY OF ASTER TATARICUS ON SCC-9 HUMAN ORAL SQUAMOUS CARCINOMA.

Background:Ephedra is among Palestinian medicinal plants that are traditionally used in folkloric medicine for treating many diseases. Ephedra is known to have antibacterial and antioxidant effects. The goal of this study is to evaluate the antioxidant activity of different extracts from the Ephedra alata plant growing wild in Palestine, and to analyze their phenolic and flavonoid constituents by HPLC/PDA and HPLC/MS.Materials and Methods:Samples of the Ephedra alata plant grown wild in Palestine were extracted with three different solvents namely, 100% water, 80% ethanol, and 100% ethanol. The extracts were analyzed for their total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity (AA), as well as phenolic and flavonoids content by HPLC/PDA/MS.Results:The results revealed that the polarity of the extraction solvent affects the TPC, TFC, and AA of extracts. It was found that both TPC and AA are highest for plant extracted with 80% ethanol, followed by 100% ethanol, and finally with 100% water. TFC however was highest in the following order: 100% ethanol > 80% ethanol > water. Pearson correlation indicated that there is a significant correlation between AA and TPC, but there is no correlation between AA and TFC. Simultaneous HPLC-PDA and UHPLC-MS analysis of the ethanolic plant extracts revealed the presence of Luteolin-7-O-glucuronide flavone, Myricetin 3-rhamnoside and some other major polyphenolic compounds that share myricetin skeleton.Conclusion:Ephedra alata extract is rich in potent falvonoid glycosidic compounds as revealed by their similar overlaid UV-Vis spectra and UHPLC-MS results. On the basis of these findings, it is concluded that Ephedra alata constitutes a natural source of potent antioxidants that may prevent many diseases and could be potentially used in food, cosmetics, and pharmaceutical products.

Identification and quantification of flavonoids in Carica papaya leaf and peroxynitrite-scavenging activity

ObjectiveTo characterize the types, contents, and peroxynitrite-scavenging activities of flavonoids in the leaf of Carica papaya (C. papaya). MethodsChromatographic and spectroscopic techniques along with high performance liquid chromatography quantitative analysis and peroxynitrite-scavenging assay were performed to isolate and quantify flavonoid compounds in the flavonoid-rich fraction (BuOH fraction) derived from MeOH extract of C. papaya leaves and evaluate their peroxynitrite-scavenging activities. ResultsSeven flavonoids were isolated from the leaves of C. papaya, including quercetin 3-(2G-rhamnosylrutinoside), kaempferol 3-(2G-rhamnosylrutinoside), quercetin 3-rutinoside, myricetin 3-rhamnoside, kaempferol 3-rutinoside, quercetin, and kaempferol. All of the substances exhibited potent activities on peroxynitrite scavenging (IC50 ≤ 4.15 μmol/L), which were stronger than the positive control, l-penicillamine (6.90 μmol/L). The content of kaempferol 3-(2G-rhamnosylrutinoside) was significantly higher than other identified compounds (123.18 mg/g BuOH fraction and 7.23 mg/g MeOH extract). ConclusionsThe results of the present study demonstrate the potent antioxidant flavonoids of C. papaya leaf, with kaempferol 3-(2G-rhamnosylrutinoside) as the major one.

Myricitrin induces antidepressant-like effects and facilitates adult neurogenesis in mice

Myricitrin (MYR) is a natural flavonoid that inhibits nitric oxide (NO) transmission and has an atypical antipsychotic-like profile in animal models. Considering that several NO inhibitors exert antidepressant-like effects, the present study evaluated the antidepressant-like effect of MYR (3–30mg/kg) in the tail suspension test (TST). Because of the putative relationship between adult neurogenesis and antidepressant activity, we also assessed cell proliferation, survival, and differentiation in adult neurogenic niches, including the subgranular zone (SGZ) and subventricular zone (SVZ). Similar to the positive control imipramine (IMI; 10mg/kg), repeated treatment with 10mg/kg MIR but not acute treatment reduced immobility time in the TST, indicating an antidepressant-like effect. No effect on general motor activity was observed. Myricitrin also facilitated cell proliferation in the SGZ of the hippocampal dentate gyrus and SVZ. In the SGZ, MYR increased the number of doublecortin- and 5-bromo-2′-deoxyuridine/neuronal nuclei-positive cells. Our results suggest that MYR facilitates hippocampal neurogenesis, which might contribute to its antidepressant-like effect and atypical antipsychotic-like profile.

Determination of myricetrin and quercitroside in Polygonum aviculare L.

Objective To establish the RP-HPLC method for the determination of myricetrin and quercitroside in Polygonum aviculare L.Methods The Agilent LC-C18 (250 mm×4.6 mm,5 μm) column was used,the mobile phase consisted of acetonitrile:0.1％ H3PO4(18 ∶ 82),the flow rate was 1.0 ml/min,the column temperature was 30℃ the detecting wavelength was at 256 nm.Results The calibration curve was linear within a range of 1.22～24.30 μg/ml and 0.77～15.40 μg/ml,the average recovery of this method was 98.9％,99.6％ and the RSD was 1.11％,1.09％,for the myricetrin and quercitroside respectively.Conclusion The method is simple,repeatable and accurate.It can be applied in quantitative determination of myricetrin and quercitroside in Polygonum aviculare L.. Key words: Polygonum aviculare L.; Myricetrin; Quercitroside; RP-HPLC

Determination of myricetrin and quercitroside in euphorbia hirta L. by RP-HPLC

Objective To establish the RP-HPLC method for the determination of myricetrin and quercitroside in Euphorbia Hirta L.Methods The ZORBAX SB-C18 (250 mm × 4.6 mm,5 μn) column was used,the mobile phase consisted of acetonitrile:0.1％ H3PO4(21 ∶ 79),the flow rate was 0.8 ml/min,the column temperature was 30℃ the detecting wavelength was at 256 nm.Results The cablibration curve was linear within a range of 0.013～0.26 mg/ml and 0.008～0.16 mg/ml,the average recovery was 99.1％,98.9％and the RSD was 0.91％,1.55％,respectively.Conclusion The method is simple,repeatable and accurate,it can be applied in quantitative determination of myricetrin and quercitroside in Euphorbia Hirta L.. Key words: Euphorbia hirta L.; Myricetrin; Quercitroside; RP-HPLC

Evaluation of antioxidant and free radical scavenging capacities of polyphenolics from pods of Caesalpinia pulcherrima.

Thirteen polyphenolics were isolated from fresh pods of Caesalpinia pulcherrima using various methods of column chromatography. The structures of these polyphenolics were elucidated as gallic acid (1), methyl gallate (2), 6-O-galloyl-d-glucoside (3), methyl 6-O-galloyl-β-d-glucoside (4), methyl 3,6-di-O-galloyl-α-d-glucopyranoside (5), gentisic acid 5-O-α-d-(6′-O-galloyl)glucopyranoside (6), guaiacylglycerol 4-O-β-d-(6′-O-galloyl)glucopyranoside (7), 3-methoxy-4-hydroxyphenol 1-O-β-d-(6′-O-galloyl) glucopyranoside (8), (+)-gallocatechin (9), (+)-catechin (10), (+)-gallocatechin 3-O-gallate (11), myricetin 3-rhamnoside (12), and ampelopsin (13). All isolated compounds were tested for their antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and peroxynitrite radicals scavenging assays. Among those compounds, 11, 12, and 2 exhibited the best DPPH-, hydroxyl-, and peroxynitrite radical-scavenging activities, respectively. Compound 7 is a new compound, and possesses better scavenging activities towards DPPH but has equivalent hydroxyl radical scavenging activity when compared to BHT. The paper is the first report on free radical scavenging properties of components of the fresh pods of Caesalpinia pulcherrima. The results obtained from the current study indicate that the free radical scavenging property of fresh pods of Caesalpinia pulcherrima may be one of the mechanisms by which this herbal medicine is effective in several free radical mediated diseases.

Online RP-HPLC-DPPH Screening Method for Detection of Radical-Scavenging Phytochemicals from Flowers of Acacia confusa

Acacia confusa is traditionally used as a medicinal plant in Taiwan. In this study, phytochemicals and antioxidant activities of extracts from flowers of A. confusa were investigated for the first time. In addition, a rapid screening method, online RP-HPLC-DPPH system, for individual antioxidants in complex matrices was developed. Accordingly, six antioxidants including gallic acid ( 1), myricetin 3-rhamnoside ( 2), quercetin 3-rhamnoside ( 3), kaempferol 3-rhamnoside ( 4), europetin 3-rhamnoside ( 5), and rhamnetin 3-rhamnoside ( 6) were detected using the developed screening method. Of these, compounds 2, 3, and 5 were found to be major bioactive phytochemicals, and their contents were determined as 11.3, 6.7, and 8.7 mg/g of crude extract, respectively. By comparison with quercetin, a well-known antioxidant, these compounds had the order of compound 2 > compound 5 > quercetin > compound 3 for DPPH radical-scavenging activity. Their IC 50 values were 3.0, 3.2, 4.5, and 7.4 microM, respectively. Moreover, the same order was observed for superoxide radical-scavenging activity, and their IC50 values were 2.6, 2.7, 4.3, and 5.3 microM, respectively. However, for lipid peroxidation, quercetin, an aglycon, showed the best inhibitory activity. The IC50 values of quercetin, compound 2, compound 5, and compound 3 were 46.7, 88.5, 90.7, and 124.6 microM, respectively. These results indicated that a rhamnoside at the C3 position of flavonoids had a negative effect on radical-scavenging activity and antilipid peroxidation. In contrast, the number of hydroxyl groups on the B-ring exhibited a positive relationship with their inhibitory activities.

Phenolic profile of hazelnut (Corylus Avellana L.) leaves cultivars grown in Portugal

In this study, phenolic compounds of hazelnut leaves of 10 different cultivars with the same cultural, geographical, geological and climatic conditions were analyzed by HPLC/DAD and HPLC/DAD/MS/MS – ESI. Eight phenolic compounds (3-caffeoylquinic acid, 5-caffeoylquinic acid, caffeoyltartaric acid, p-coumaroyltartaric acid, myricetin 3-rhamnoside, quercetin 3-glycoside, quercetin 3-rhamnoside and kaempferol 3-rhamnoside) were identified and quantified. All of the analyzed samples showed a similar phenolic profile, in which myricetin 3-rhamnoside and quercetin 3-rhamnoside were the major compounds and caffeoyltartaric and p-coumaroyltartaric acids were present in vestigial amounts.

Flavonol glycosides from Lysimachia congestiflora

Two new flavonol glycosides, larycitrin 3- O- α-arabinofuranoside and syringetin 3- O- α-rhamnopyranosyl(1 → 5)- α-arabinofuranoside, together with syringetin and six known flavonol glycosides, kaempferol 3- O- α-arabinofuranoside, myricetin 3-rhamnoside and 3- O-arabinofuranoside, syringetin 3- O- α-arabinofuranoside and 3-rhamnoside, and larycitrin 3-rhamnoside were isolated from the whole plant of Lysimachia congestiflora. All structures were established on the basis of UV, MS and NMR spectral analyses.

A flavonol glycoside from Myrsine africana leaves

Myricetin 3-(3″,4″-diacetylrhamnoside), a novel flavonol glycoside together with myricetin 3-rhamnoside, myricetin 7-rhamnoside, myricetin 3-xyloside, myricetin 3-arabinoside, quercetin 3-galactoside, 3′- O -methylquercetin 3-glucoside, myricetin, quercetin, kaempferol and gallic acid have been isolated from a methanolic extract of Myrsine africana leaves.

Two phloroglucinol glucosides, flavan gallates and flavonol glycosides from Sedum sediforme flowers

Two new compounds, whose structures were elucidated by spectroscopic means as 1-β- d-gluco pyranosyloxy-3-methoxy- 5-hydroxybenzene and (2 R,3 R)-7,4′-dihydroxy-5,3′,5′-trimethoxyflavan 3- O-gallate, were isolated from Sedum sediforme flowers. They were accompanied by 1-β- d-glucopyranosyloxy-3,5-dihydroxybenzene, limocitrin 3- glucoside, kaempferol 3-rhamnoside, quercetin 3-rhamnoside, myricetin 3-rhamnoside, (−)-epicatechin 3-gallate, (−)- epigallocatechin 3-gallate and gallic acid.

Flavonoid profiles of new zealand Libocedrus and related genera

Flavonoids common to both Libocedrus bidwillii and L. plumosa, which were sampled throughout New Zealand, are: kaempferol and quercetin 3-rhamnoside, kaempferol and quercetin 3-rhamnoside-7-glucoside, quercetin 3-glucoside, apigenin and luteolin 7-glucoside, luteolin 7-di- (and tri)-glucosides, amentoflavone, 7- O-methylamentoflavone, 2,3-dihydroamentoflavone, and the new flavonoids, 8-hydroxyapigenin and 8-hydroxyluteolin 7- O-xylosides and 7- O-methyl-2,3-dihydroamentoflavone. Libocedrus plumosa is distinguished by the additional accumulation of myricetin 3-rhamnoside, and L. bidwillii by the presence of quercetin 3- O-α-[2- p-hydroxybenzoyl-4- O- p-coumaroylrhamnopyranoside] which was found amongst the biflavones. A chromatographic survey of some related non-New Zealand species and genera is also reported.