Quercetin Aglycone Research Articles

Changes in rutin concentration and flavonol-3-glucosidase activity during seedling growth in tartary buckwheat (Fagopyrum tataricum Gaertn.)

To investigate the physiological roles of rutin (quercetin 3-O-rutinoside) and flavonol-3-glucosidase (f3g, a rutin-degrading enzyme) during cotyledon growth in tartary buckwheat, changes in rutin and quercetin (aglycone of rutin) concentrations, and f3g activities were measured. The rutin concentration gradually increased (about 50 mg g-1 DW cotyledons) up to 12 d after germination (DAG). The quercetin concentration in the tartary buckwheat cotyledon increased immediately after germination, reached a maximum at 4 DAG, and then remained around 1.5 mg g-1 DW until 12 DAG. The f3g activity in the cotyledon and testa decreased gradually after germination. However, it retained 80% activity at 4 DAG compared with dry seed. In addition, the f3g activity was high on the surface of the cotyledon. We also investigated spatial distribution of rutin and f3g activity in 4 DAG seedlings. While rutin was mostly present in the cotyledon, f3g activity was observed in the testa, the surface of the testa, and root. These results suggest that rutin and f3g activity in tartary buckwheat have different physiological roles during cotyledon growth compared with common buckwheat. Key words: Tartary buckwheat; rutin; quercetin; flavonoid; glucosidase; germination

Evaluation of a Method to Determine Flavonol Aglycones in Ginkgo biloba Dietary Supplement Crude Materials and Finished Products by High-Performance Liquid Chromatography: Collaborative Study

An interlaboratory study was conducted for evaluation of a method to determine the flavonol aglycones quercetin, kaempferol, and isorhamnetin in Ginkgo biloba products. The method calculates total glycosides based on these aglycones formed after acid hydrolysis. Twelve matrixes were chosen for study by 12 collaborating laboratories in 2 countries. Test materials included crude leaf material, standardized dry powder extract, single and multiple entity finished products, ethanol and glycerol tinctures, and National Institute of Standards and Technology (NIST) standard reference materials (SRMs). Results from 11 laboratories were used for the final calculations. Eight of the 12 matrixes evaluated produced acceptable results for total flavonol glycosides, with HorRat scores ranging from 1.31 to 2.05; repeatability relative standard deviations (RSDr) from 1.46 to 4.14; and reproducibility relative standard deviations (RSDR) from 4.67 to 9.69. These 8 matrixes consisted primarily of simple dosage forms (e.g., dry powder extracts, crude leaf samples, liquid extracts, and SRMs) and a single tablet product (Ginkgo Awareness). Four additional matrixes, consisting of 3 tablets and 1 soft gel product (Ginkgold, Ginkoba, Ginkogen, and Ginkgo Phytosome, respectively), showed greater total flavonol glycoside HorRat scores in comparison, ranging from 2.39 to 5.13, with RSDr values from 2.83 to 8.16, and RSDR values from 8.53 to 20.4. Based on the results presented here, the method is recommended for Official First Action for determination of total flavonol glycosides calculated from quercetin, kaempferol, and isorhamnetin in dry powder extracts, crude leaf material, liquid extracts, and a select finished product, Ginkgo Awareness.

Effects of cultivar, lifting time and nitrogen fertiliser level on quercetin content in onion (Allium cepa L.) at lifting

AbstractCommercial cultivars of onion (Allium cepa L.) were grown at Torslunda research station, Sweden with different levels of nitrogen fertiliser and lifted at different growth stages. Soon after lifting, before any drying or curing, tissue from the fleshy edible part of onions was extracted in ethanol and the raw extracts were analysed by high‐performance liquid chromatography without any previous hydrolysis. It was confirmed that the main flavonoid compounds were quercetin monoglucoside and quercetin diglucoside, whereas only trace amounts of quercetin aglycone and other flavonoids were found. The greatest variation in quercetin content, in the range 100–500 mg kg−1 fresh weight, occurred between years. The concentration of quercetin glucosides in the onions was strongly correlated (R2 = 0.98) with the total amount of global radiation in August. Individual onions with fallen leaves had significantly higher concentrations of quercetin glucosides than individuals in the same row with erect leaves. Only minor differences were found between the three cultivars analysed. Higher levels of nitrogen fertiliser had only minor effects on onion yield and size and resulted in lower or equal amounts of quercetin glucosides. Nitrogen leakage from the soil, a potential source of environmental problems, could therefore be minimised by avoiding high nitrogen fertiliser levels with almost no effect on onion flavonol content. Late lifting of onions (80% fallen leaves) resulted in up to 45% higher concentrations of quercetin glucosides compared with early lifting (50% fallen leaves). Copyright © 2006 Society of Chemical Industry

Three-Year Comparison of the Content of Antioxidant Microconstituents and Several Quality Characteristics in Organic and Conventionally Managed Tomatoes and Bell Peppers

Understanding how the environment and production and cultivation practices influence the composition and quality of food crops is fundamental to the production of high-quality nutritious foods. In this 3-year study, total phenolics, percent soluble solids, ascorbic acid, and the flavonoid aglycones quercetin, kaempferol, and luteolin were measured in two varieties of tomato (Lycopersicon esculentum L. cv. Ropreco and Burbank) and two varieties of bell peppers (Capsicum annuum L. cv. California Wonder and Excalibur) grown by certified organic and conventional practices in a model system. Significantly higher levels of percent soluble solids (17%), quercetin (30%), kaempferol (17%), and ascorbic acid (26%) were found in Burbank tomatoes (fresh weight basis; FWB), whereas only levels of percent soluble solids (10%) and kaempferol (20%) were significantly higher in organic Ropreco tomatoes (FWB). Year-to-year variability was significant, and high values from 2003 influenced the 3-year average value of quercetin reported for organic Burbank tomatoes. Burbank tomatoes generally had higher levels of quercetin, kaempferol, total phenolics, and ascorbic acid as compared to Ropreco tomatoes. Bell peppers were influenced less by environment and did not display cropping system differences.

Pharmacological in vivo test to evaluate the bioavailability of some St. John's wort innovative oral preparations

Preparations based on extracts of St. John's wort are widely marketed for treating mild to moderately severe depressive disorders and other health conditions such as anxiety and sleep disorders [1]. Active principles are not yet discovered and flavonols, based on quercetin aglycone, naphthodianthrones (hypericin and pseudohypericin) and phloroglucinols such as hyperforin, adhyperforin seems to be related to this action. Thus, flavonols and naphthodianthrones are polyphenols, quite polar derivatives but their water solubility is very scarce; phloroglucinols are lipophilic and completely not water-soluble constituents. In addition, hypericins and hyperforins are not stable with regard to heat and light [2].

Effects of various flavonoids on xanthine oxidase activities in vitro and on plasma uric acid levels in oxonate-induced rats

Xanthine oxidase (XO) is the key enzyme that catalyzes the oxidation of xanthine and hypoxanthine into uric acid, and plays an important role in producing hyperuricemia and gout [1]. It has been shown in the literature that flavonoids showed potent XO inhibitory activities in vitro [2]. However, less information about the in vivo hypouricemic activities of flavonoids are available. In the present study it was therefore of interest to investigate if the in vitro XO inhibitory activities of various flavonoids can be correlated with hypouricemic effects in vivo. Eight flavonoids including flavones, flavonols, and flavanones were used to inhibit the XO activity in vitro. The aglycones luteolin, apigenin, kaempferol and quercetin were shown to have potent xanthine oxidase inhibitory activities with IC50 values less than 5µM. Glycosides such as luteolin-7-O-glucoside and rutin showed weaker activities with IC50 value greater than 20µM. Eriodictyol and naringenin showed low activities with IC50 value greater than 50µM. All compounds were administered orally to oxonate-induced hyperuricemic rats at doses of 50 and 100mg/kg. None of the tested flavonoids elicited any hypouricemia in vivo after oral administration. This lack of effect might be due to the low intestinal absorption of the flavonoids or the first pass effect through the liver.

The antileishmanial activity assessment of unusual flavonoids from Kalanchoe pinnata

The importance of flavonoids for the antileishmanial activity of Kalanchoe pinnata was previously demonstrated by the isolation of quercitrin, a potent antileishmanial flavonoid. In the present study, the aqueous leaf extract from the medicinal plant K. pinnata (Crassulaceae) afforded a kaempferol di-glycoside, named kapinnatoside, identified as kaempferol 3- O-α- l-arabinopyranosyl (1 → 2) α- l-rhamnopyranoside ( 1). In addition, two unusual flavonol and flavone glycosides already reported, quercetin 3- O-α- l-arabinopyranosyl (1 → 2) α- l-rhamnopyranoside ( 2) and 4′,5-dihydroxy-3′,8-dimethoxyflavone 7- O-β- d-glucopyranoside ( 3), have been isolated. Their structures were determined via analyses of mono and bi-dimensional 1H and 13C NMR spectroscopic experiments and HR-MALDI mass spectra. Because of its restricted occurrence and its abundance in K. pinnata, flavonoid ( 2) may be a chemical marker for this plant species of high therapeutic potential. The three flavonoids were tested separately against Leishmania amazonenis amastigotes in comparison with quercitrin, quercetin and afzelin. The quercetin aglycone – type structure, as well as a rhamnosyl unit linked at C-3, seem to be important for antileishmanial activity.

Assessment of the DNA damaging potency and chemopreventive effects towards BaP-induced genotoxicity in human derived cells by Monimiastrum globosum, an endemic Mauritian plant

Naturally occurring compounds have protective effects towards mutagens and carcinogens. The leaf extract of Monimiastrum globosum (Bois de Clous), a Mauritian endemic plant from the Myrtaceae family, was studied for its potency to induce DNA damage in human HepG2 hepatoma cells using DNA migration as a biological endpoint in the alkaline single cell gel electrophoresis (SCGE) assay. This was contrasted with the ability to modulate the benzo[a]pyrene (BaP)-dependent DNA damage in human hepatoma cells. M. globosum caused genotoxicity in HepG2 cells at concentrations exceeding 3 mg fresh weight (FW) per ml cell culture in the absence of cytotoxicity. Pre-treatment of the cells with 12.2 μg FW/ml to 1.56 mg FW/ml led to a pronounced antigenotoxic effect towards BaP-induced DNA damage. DNA migration (OTM) was reduced by 66%, 81.5% and 74% for 49, 98 and 195 μg FW/ml, respectively. A U-shaped dose-response curve was derived for M. globosum indicating genotoxic effects in high doses and antigenotoxic effects in low doses. M. globosum extract had total phenolics (15 mg/g FW) with flavonoids (aglycones and conjugates: 8 mg/g FW) and proanthocyanidins (3 mg/g FW) as major phenolic subclasses. The hydrolysis of conjugated flavonoids yielded the aglycones quercetin (606 μg/g FW) and kaempferol (117.8 μg/g FW) while HPLC-MS/MS analysis of the total extract revealed free flavonoids such as quercetin (19.2 μg/g FW) and myricetin (2.5 μg/g FW). The antioxidant activity of the extract of M. globosum, assessed by the FRAP and TEAC assays yielded values of 275 ± 3.82 μmol/g FW and 346 ± 4.2 μmol/g FW, respectively.

Metabolism of quercetin and rutin by the pig caecal microflora prepared by freeze-preservation

Several studies confirm a protection of cardiovascular diseases and certain forms of cancer by dietary flavonoid intake. The bioavailability of flavonoids is influenced by the metabolism of the microflora in the intestine. Using a new in vitro model system the deglycosylation of the flavonol rutin and the degradation of its aglycone quercetin were investigated by using fresh pig caecal inocula in comparison to inocula prepared before by freeze-preservation between 6 wk and 5 months. The incubation experiments led to the same pattern of phenolic degradation products in comparable amounts in both preparations using HPLC-DAD and GC-flame ionization detection (GC-FID) or GC-MS detection within 24-48 h of incubation. With the preservation of the microbial vitality and the metabolic efficiency by freeze-preparation over several months the experimental design of microbial metabolism studies will be independent in time and locality.

In vitro degradation of the flavonol quercetin and of quercetin glycosides in the porcine hindgut

The present study investigated the microbial degradation of the plant flavonol quercetin and its naturally occurring glycosides isoquercitrin and rutin in the porcine hindgut. The experiments were carried out with the semicontinuous colon-simulation technique. The fluid and particle phase of pig hindgut contents from freshly slaughtered animals were used for the in vitro incubations. Following a five-day equilibration period, quercetin, isoquercitrin or rutin were administered to fermentation vessels and their turnover rate was determined. None of the flavonols affected parameters of microbial fermentation like pH, redox potential or VFA production. The turnover rate for isoquercitrin was seven times higher than the turnover for the fermentation fluid. The turnover rates for quercetin and rutin were four and twofold higher than fluid turnover, respectively. After administration of isoquercitrin or rutin, their aglycone quercetin was detected as an intermediary metabolite. Under sterile conditions using autoclaved incubation fluids and hindgut contents, turnover rates for quercetin and rutin were still higher than the fluid turnover in the fermentation vessels. This indicates a certain chemical instability of the flavonols and/or adsorption to ingesta particles. Thus, flavonols are subjected to microbial metabolism in the porcine hindgut. The glycosidic structure strongly influences the rate of metabolism.

Analysis of flavonoids in the mature fruit of Vaccinium uliginosum L. of China

In this study, a new extraction method was developed and two kinds of flavonoids were extracted from the mature fruit of Vaccinium uliginosum L. of China. These two kinds of flavonoids were analyzed by spectral and identified by high-performance liquid chromatography (HPLC) and UV/Vis. The extract of the fruit was total acid hydrolyzed. TLC chromatography was subsequently employed to identify the hydrolysate. Two kinds of aglycone flavonoids, quercetin and myricetin, were identified. At the same time PC chromatography was used to identify the monomer sugar in the flavonoids and it was verified as glucose. HPLC, UV/Vis, and Mass spectrum analyses revealed that the flavonoids were quercetin 3-monoglucosides and myricetin 3-monoglucosides.

Molecular Dynamics Simulations on the Coplanarity of Quercetin Backbone for the Antioxidant Activity of Quercetin-3-monoglycoside

Flavonoids are a broad class of low molecular weight, secondary plant phenolics characterized by the flavan nucleus. The family includes flavanols, flavanones, anthocyanidines, flavones, and flavonols. Most of the beneficial effects of flavonoids are attributed to their antioxidant abilities. The flavonoids contain a number of phenolic hydroxyl groups attached to ring structures, conferring the antioxidant activity. Among these flavonoid families, flavonols are found in almost every plant. The most commonly occurring flavonols are those with dihydroxylation in the 3' and 4' positions of B ring and the preferred glycosylation site on the flavonoids is the 3 position. It has been reported that the hydroxyl group at position 3 is required for the maximal radical scavenging activity of flavonols. Quercetin is a representative flavonol with high antioxidant activity. Therefore, we focused on the conformation of quercetin and quercetin-3-monoglycoside to investigate the effect of glycosylation of quercetin on their antioxidant activity. Structure-antioxidant activity relationships of flavonoids have been extensively reported. Generally, antioxidant activity depends on the number and positions of hydroxyl groups and other substituents, and glycosylation of flavonoid molecules. Glucose is the most usual sugar residue but others include galactose and rhamnose. Aside from other factors which can affect the activity, it is generally known that glycosylation of flavonoids diminishes their antioxidant activity when compared to the corresponding aglycones, perhaps since this reduces the number of free hydroxyl groups and also the linkage of sugar may hinder access of the free radical scavengers to the radical center. As mentioned above, there are several and complicated factors which affect the antioxidant activity of flavonol. Conjugation between the Aand B-rings permits a resonance effect of the aromatic nucleus that lends stability to the flavonoid radical. van Acker et al. suggested that the removal of the 3 hydroxyl group or other substituents interfere with the coplanarity of the B-ring with the rest of the flavonoid and the ability to delocalize electrons. They calculated the geometry using quantum chemical calculation which cannot include the solvent effects and shows only optimized conformation. The flavonols are conformationally flexible and their conformations are influenced by the intermolecular environment. Thus, a range of torsion angle of backbone can be observed for the same flavonol in different environments. Therefore, we pursue the trajectories during the molecular dynamics simulations in aqueous environment and investigate the coplanarity of quercetin’s backbone and conformations in order to find out the relationship between the conformation and antioxidant activity. It is difficult to compare the antioxidant activities of flavonols between the results of one author and others because of different experimental condition, methods, and skill. Therefore, we selected one reference which use two different methods and obtained similar results. Six flavonols are investigated by molecular dynamic simulations and their chemical structures and abbreviations are shown in Figure 1. Quercetin aglycone has the most potent antioxidant activity in flavonol aglycones. The structure of quercetin was elucidated by crystal and molecular modeling. The exocyclic B ring of quercetin exists in an almost planar conformation with respect to the rest of the molecule. Quercetin not only has 3-hydroxyl group in the C-ring and 3',4'-dihydroxy groups in the B-ring, but also possess the 2,3-double bond in conjugation with 4-oxo function in the C-ring (Figure 1), which are the essential structural elements for potent radical

In-vitro effect of flavonoids from Solidago canadensis extract on glutathione S-transferase

Solidago canadensis is typical of a flavonoid-rich herb and the effect of an aqueous ethanol extract on glutathione-S-transferase (GST) activity using HepG2 cells was compared with those of the flavonol quercetin and its glycosides quercitrin and rutin, found as major constituents. The composition of the extract was determined by HPLC and rutin was found to be the major flavonoidal component of the extract. Total GST activity was assessed using 1-chloro-2,4-dinitrobenzene as a substrate. The glycosides rutin and quercitrin gave dose-dependent increases in GST activity, with a 50% and 24.5% increase at 250 mM, respectively, while the aglycone quercetin inhibited the enzyme by 30% at 250 mM. The total extract of the herb gave an overall dose-dependent increase, the fractions corresponding to the flavonoids showed activating effects while those containing caffeic acid derivatives were inhibitory. The activity observed corresponds to that reported for similar compounds in-vivo using rats, thus the HepG2 cell line could serve as a more satisfactory method of assessing the effects of extracts and compounds on GST.

Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent formation of reactive oxygen species in differentiated PC-12 cells

To assess the efficacy of conjugated quercetin metabolites as attenuators for oxidative stress in the central nervous system, we measured the 13-hydroperoxyoctadecadienoic acid (13-HPODE)-dependent formation of reactive oxygen species (ROS) in pheochromocytoma PC-12 cells in the presence of quercetin 3-O-β-glucuronide (Q3GA) and related compounds. A 2′,7′-dichlorofluorescin (DCFH) assay showed that Q3GA significantly suppressed the formation of ROS, when it was coincubated with 13-HPODE (coincubation system). However, it was less effective than quercetin aglycon in the concentration range from 0.5 to 10 μM. In an experiment in which the cells were incubated with the test compounds for 24 h before being exposed to 13-HPODE, Q3GA was also effective in suppressing the formation of ROS in spite that little Q3GA was taken up into the cells. These results suggest that antioxidative metabolites of quercetin are capable of protecting nerve cells from attack of lipid hydroperoxides.

Hypericum Perforatum: A ???Modern??? Herbal Antidepressant

Hypericum perforatum (St John's Wort [SJW]) counts among the most favourite herbal drugs, and is the only herbal alternative to classic synthetic antidepressants in the therapy of mild to moderate depression. Several clinical studies have been conducted to verify the effectiveness of ethanolic or methanolic extracts of SJW. Alcoholic SJW extracts are a mixture of substances with widely varying physical and chemical properties and activities. Hyperforin, a phloroglucinol derivative, is the main source of pharmacological effects caused by the consumption of alcoholic extracts of SJW in the therapy of depression. However, several studies indicate that flavone derivatives, e.g. rutin, and also the naphthodianthrones hypericin and pseudohypericin, take part in the antidepressant efficacy. In contrast to the amount of documentation concerning clinical efficacy, oral bioavailability and pharmacokinetic data about the active components are rather scarce. The hyperforin plasma concentration in humans was investigated in a small number of studies. The results of these studies indicate a relevant plasma concentration, comparable with that used in in vitro tests. Furthermore, hyperforin is the only ingredient of H. perforatum that could be determined in the brain of rodents after oral administration of alcoholic extracts. The plasma concentrations of the hypericins were, compared with hyperforin, only one-tenth and, until now, the hypericins could not be found in the brain after oral administration of alcoholic H. perforatum extracts or pure hypericin. Until now, the pharmacokinetic profile of the flavonoids in humans after oral administration of an alcoholic H. perforatum extract has been investigated in only one study. More data are available for rutin and the aglycone quercetin after administration of pure substances or other flavonoid sources.

Chemical characterization of commercial dietary ingredients from Vitis vinifera L.

In recent years a large number of commercial products containing ingredients from winery byproducts have proliferated in the market. However, little research has focused on studying the phenolic composition of these products and there is still no legislation concerning their commercialization. In this work, a wide range of commercial ingredients derived from Vitis vinifera L. grape seeds ( n = 16) and skins ( n = 4), grape pomace ( n = 6) and leaves ( n = 3) as well as different production batches of some of them, have been analyzed. Gallic acid, monomeric flavan-3-ols ((+)-catechin, (−)-epicatechin and epicatechin-3- O-gallate), procyanidins dimers (B3, B1, B4, B2, B3′-3- O-gallate), and trimers (T2 and C1) were identified in ingredients derived from grape seeds. These ingredients were comprised of fractions enriched either in monomeric, oligomeric or polymeric flavan-3-ols, with a mean degree of polymerization (mDP) ranging from 2.1 to 11.2. Grape anthocyanins (delphinidin, cyanidin, petunidin, peonidin and malvidin-3-glucosides, -3-(6-acetyl)-glucosides and -3-(6- p-coumaroyl)-glucosides, and peonidin and malvidin-3-(6-caffeoyl)-glucosides) were identified in ingredients derived from non-processed grape skins whereas grape pomace ingredients also contained anthocyanin-derived pigments (the pyruvate, vinylcatechol, vinylepicatechin, vinylphenol and vinylguaiacol derivatives of malvidin-3-glucoside, and malvidin-3-(6-acetyl)-glucoside-vinylepicatechin). In the case of the ingredients of leaves, anthocyanins (delphinidin, cyanidin, petunidin, peonidin and malvidin-3-glucosides and -3-(6- p-coumaroyl)-glucosides, and cyanidin and peonidin-3-(6-acetyl)-glucosides), and non-anthocyanin compounds ( trans-caftaric acid, and the -3- O-galactoside, -glucuronide and -glucoside derivatives of quercetin and kaempherol, and quercetin aglycone) were identified; the relationship between the two types of compounds (anthocyanin/flavonol) differed in the distinct ingredients studied. Despite the large variability found between the different brands of ingredients derived from a particular byproduct, all of the ingredients studied were authentically derived from the V. vinifera L. spp.

A solid-phase extraction-thin-layer chromatographic-fiber optical scanning densitometric method for determination of flavonol aglycones in extracts of rose leaves

Summary A qualitative and quantitative analytical procedure using thin-layer chromatography in combination with fiber optical scanning densitometry is presented for identification of, mainly, flavonol aglycones (quercetin and kaempferol) in extracts from rose leaves. Preliminary cleaning of the extracts was necessary to remove matrix components; SPE was used for this purpose. The compounds were identified by automatic measurement and computer-based comparison of in-situ UV spectra with reference spectra using a cross-correlation function. For amounts between 1 and 10 µg spot–1 there were no differences between in-situ UV spectra acquired for kaempferol but some differences were observed for quercetin.

Effect of Ginkgo biloba extract on procarcinogen-bioactivating human CYP1 enzymes: Identification of isorhamnetin, kaempferol, and quercetin as potent inhibitors of CYP1B1

In the present study, we investigated the effect of Ginkgo biloba extracts and some of its individual constituents on the catalytic activity of human cytochrome P450 enzymes CYP1B1, CYP1A1, and CYP1A2. G. biloba extract of known abundance of terpene trilactones and flavonol glycosides inhibited 7-ethoxyresorufin O-dealkylation catalyzed by human recombinant CYP1B1, CYP1A1, and CYP1A2, and human liver microsomes, with apparent Ki values of 2 +/- 0.3, 5 +/- 0.5, 16 +/- 1.4, and 39 +/- 1.2 microg/ml (mean +/- SE), respectively. In each case, the mode of inhibition was of the mixed type. Bilobalide, ginkgolides A, B, C, and J, quercetin 3-O-rutinoside, kaempferol 3-O-rutinoside, and isorhamentin 3-O-rutinoside were not responsible for the inhibition of CYP1 enzymes by G. biloba extract, as determined by experiments with these individual chemicals at the levels present in the extract. In contrast, the aglycones of quercetin, kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1 (apparent Ki = 3 +/- 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent Ki = 418 +/- 50 nM). The mode of inhibition was competitive, noncompetitive, or mixed, depending on the enzyme and the flavonol. G. biloba extract also reduced benzo[a]pyrene hydroxylation, and the effect was greater with CYP1B1 than with CYP1A1 as the catalyst. Overall, our novel findings indicate that G. biloba extract and the flavonol aglycones isorhamnetin, kaempferol, and quercetin preferentially inhibit the in vitro catalytic activity of human CYP1B1.

Quercetin appears in the lymph of unanesthetized rats as its phase II metabolites after administered into the stomach

Quercetin is a major flavonoid in plant foods and potentially has beneficial effects on disease prevention. The present work demonstrated that quercetin was transported into the lymph after being metabolized in the gastrointestinal mucosa of rats. Glucuronide/sulfate and methylated conjugates of quercetin appeared in the lymph, but not quercetin aglycone. The highest lymphatic concentration was found at as rapid as 30 min after administration, suggesting gastric absorption, whereas the mucosal glucuronidation activity was significantly higher in the duodenum and jejunum than in the stomach. This is the first report to show the lymphatic flavonoid transport pathway from the gastrointestinal tract.

Simultaneous Quantification of Terpenelactones and Flavonol Aglycones in Hydrolyzed Ginkgo biloba Extract by Liquid Chromatography with Inline Ultraviolet and Evaporative Light Scattering Detection

We report here a liquid chromatography (LC) method with inline ultraviolet/evaporative light scattering (UV/ELS) detection for the simultaneous quantification of the terpenelactones and flavonol aglycones in a single sample of hydrolyzed Ginkgo biloba extract (GBE). The sample is hydrolyzed by a rapid and convenient oven heating method for 1 h at 90 degrees C with 10% hydrochloric acid. The 1 h hydrolysis was found to be equivalent to the 2.25 h reflux treatment for dry powder extract, where total flavonol glycosides were 28.4 and 28.1%, respectively. Acceptable precision was achieved for total terpenelactones [relative standard deviation (RSD) = 4.8%] by ELS detection, and total flavonol aglycones (RSD = 2.3%) by UV detection. The analytical range was 1.5 to 7.3% (w/w) for the individual terpenelactones (ELS) and 2.5 to 15.0% (w/w) for the individual glycosides (UV) calculated from the aglycones quercetin, kaempferol, and isorhamnetin. This improved method allows for the first time high throughput sample preparation coupled with the quantification of the predominant compounds generally used for quality control of GBE in a single assay.