Tea Flavonols Research Articles

Enhancing the effect of catechins with green tea flavonol and polysaccharides on preventing lipid absorption and accumulation

The hypothesis of the current study was that flavonol and polysaccharides obtained during catechins extraction from green tea may enhance the effect of catechins on preventing pancreatic lipase activity, free glycerol absorption and accumulation in adipocytes co-cultured with Caco-2 cell after in vitro digestion. Catechins rich extract from green tea (GCT: 10 mg), GCT formulated with polysaccharides (GTP: 1 mg) and flavonol extract (GFV: 0.1 mg) strongly inhibited lipase activity during digestion while increasing lipolysis in adipocytes. Lipid accumulation in adipocytes was significantly reduced in GCT (10 mg) + GTP (1 mg) + GFV (1 mg) (100–87.27%) compared to control (p < 0.05). When targeted single flavonols (myricetin, quercetin, and kaempferol) were added into catechins in GCT (EGCG), the lipid accumulation in adipocyte ranged from 82.07 to 89.11% of control. EGCG (3 mg) + Quercetin (0.3 mg) transported the lowest amount of glycerol (2.18 ± 0.18 mM) in aqueous fraction from the digesta to the Caco-2 cell. Results from the current study suggested that co-consumption of catechin rich green tea extracts with by-products including flavonols and polysaccharides obtained during green tea processing could be potential natural components on anti-obesity by preventing lipid intestinal absorption and accumulation in adipocytes.

Functional characterization of three flavonol synthase genes from Camellia sinensis: Roles in flavonol accumulation

Flavonol derivatives are a group of flavonoids benefiting human health. Their abundant presence in tea is associated with astringent taste. To date, mechanism pertaining to the biosynthesis of flavonols in tea plants remains unknown. In this study, we used bioinformatic analysis mining the tea genome and obtained three cDNAs that were annotated to encode flavonol synthases (FLS). Three cDNAs, namely CsFLSa, b, and c, were heterogenously expressed in E. coli to induce recombinant proteins, which were further used to incubate with three substrates, dihydrokampferol (DHK), dihydroquercetin (DHQ), and dihydromyricetin (DHM). The resulting data showed that three rCsFLSs preferred to catalyze (DHK). Overexpression of each cDNA in tobacco led to the increase of kampferol and the reduction of anthocyanins in flowers. Further metabolic profiling of flavan-3-ols in young tea shoots characterized that kaempferol derivatives were the most abundant, followed by quercetin and then myricetin derivatives. Taken together, these data characterized the key step committed to the biosynthesis of flavonols in tea leaves. Moreover, these data enhance understanding the metabolic accumulation relevance between flavonols and other main flavonoids such as flavan-3-ols in tea leaves.

Active phlorotannins from seven brown seaweeds commercially harvested in Brittany (France) detected by 1H NMR and in vitro assays: temporal variation and potential valorization in cosmetic applications

This study was focused on the phenolic content and associated cosmetic activities of seven brown marine macroalgae: Alaria esculenta, Ascophyllum nodosum, Bifurcaria bifurcata, Fucus serratus, Halidrys siliquosa, Himanthalia elongata, and Laminaria ochroleuca, selected for their abundance in Brittany and their phlorotannin production. Phlorotannins were extracted by maceration followed by a liquid/liquid purification to obtain fractions enriched in phlorotannins. Seasonal and yearly variations in phenolic contents were investigated thanks to the Folin-Ciocalteu assay to find the best harvesting season for each species. 1H nuclear magnetic resonance (NMR) was used to validate the presence of phenolic compounds and to compare the species in terms of phenolic signals, as they produce different phlorotannin molecules. Activities required for cosmetic applications (i.e., radical scavenging, antioxidant, photoprotective, and anti-aging activities) were assessed by in vitro tests. Fucales, especially A. nodosum, F. serratus, H. elongata, and H. siliquosa, showed higher phenolic contents than Laminariales. Temporal variations were apparent for five seaweeds with the highest phenolic content, notably in autumn. The phenolic content was high regardless of the season and antioxidant and photoprotective activities were similar to those of commercial molecules, allowing year-round algal harvesting. The anti-aging activity of A. nodosum and F. serratus fractions was higher than the active tea flavonol, epigallocatechin gallate. These results are promising for the use of abundant marine macroalgae as a source of natural active ingredients for cosmetic applications.

Stability and Fermentability of Green Tea Flavonols in In-Vitro-Simulated Gastrointestinal Digestion and Human Fecal Fermentation.

Flavonols, the second most abundant flavonoids in green tea, exist mainly in the form of glycosides. Flavonols are known to have a variety of beneficial health effects; however, limited information is available on their fate in the digestive system. We investigated the digestive stability of flavonol aglycones and glycosides from green tea under simulated digestion and anaerobic human fecal fermentation. Green tea fractions rich in flavonol glycosides and aglycones, termed flavonol-glycoside-rich fraction (FLG) and flavonol-aglycone-rich fraction (FLA) hereafter, were obtained after treatment with cellulase and tannase, respectively. Kaempferol and its glycosides were found to be more stable in simulated gastric and intestinal fluids than the derivatives of quercetin and myricetin. Anaerobic human fecal fermentation with FLG and FLA increased the populations of Lactobacilli spp. and Bifidobacteria spp. and generated various organic acids, such as acetate, butyrate, propionate, and lactate, among which butyrate was produced in the highest amount. Our findings indicate that some stable polyphenols have higher bioaccessibilities in the gastrointestinal tract and that their health-modulating effects result from their interactions with microbes in the gut.

Antioxidative, Anti-Inflammatory, and Anticancer Effects of Purified Flavonol Glycosides and Aglycones in Green Tea.

(1) Background: Extensive research has focused on flavan-3-ols, but information about the bioactivities of green tea flavonols is limited. (2) Methods: In this study, we investigated the antioxidative, anti-inflammatory, and anticancer effects of flavonol glycosides and aglycones from green tea using in vitro cell models. The fractions rich in flavonol glycoside (FLG) and flavonol aglycone (FLA) were obtained from green tea extract after treatment with tannase and cellulase, respectively. (3) Results: FLG and FLA contained 16 and 13 derivatives, respectively, including apigenin, kaempferol, myricetin, and quercetin, determined by mass spectrometry. FLA exhibited higher radical-scavenging activity than that of FLG. FLG and FLA attenuated the levels of intracellular oxidative stress in neuron-like PC-12 cells. The treatment of RAW 264.7 murine macrophages with FLG and FLA significantly reduced the mRNA expression of inflammation-related genes in a dose-dependent manner. Furthermore, FLG and FLA treatments decreased the viability of the colon adenoma cell line DLD-1 and breast cancer cell line E0771. Moreover, the treatment with FLG or FLA combined with paclitaxel had synergistic anticancer effects on the DLD-1 cell line. (4) Conclusions: Flavonols from green tea exerted beneficial effects on health and may be superior to flavan-3-ols.

Dyrk1A overexpression leads to increase of 3R-tau expression and cognitive deficits in Ts65Dn Down syndrome mice

Alternative splicing of tau exon 10 generates tau isoforms with three or four microtubule-binding repeats, 3R-tau and 4R-tau, which is equally expressed in adult human brain. Imbalanced expression in 3R-tau and 4R-tau has been found in several sporadic and inherited tauopathies, suggesting that dysregulation of tau exon 10 is sufficient to cause neurodegenerative diseases. We previously reported that Dyrk1A, which is overexpressed in Down syndrome brains, regulates alternative splicing of exogenous tau exon 10. In the present study, we investigated the regulation of endogenous tau exon 10 splicing by Dyrk1A. We found that inhibition of Dyrk1A enhanced tau exon 10 inclusion, leading to an increase in 4R-tau/3R-tau ratio in differentiated-human neuronal progenitors and in the neonatal rat brains. Accompanied with overexpression of Dyrk1A, 3R-tau was increased and 4R-tau was decreased in the neonatal brains of Ts65Dn mice, a model of Down syndrome. Treatment with Dyrk1A inhibitor, green tea flavonol epigallocatechin-gallate (EGCG), from gestation to adulthood suppressed 3R-tau expression and rescued anxiety and memory deficits in Ts65Dn mouse brains. Thus, Dyrk1A might be an ideal therapeutic target for Alzheimer’s disease, especially for Down syndrome and EGCG which inhibits Dyrk1A may have potential effect on the treatment or prevention of this disease.

Reducing Breast Cancer Recurrence: The Role of Dietary Polyphenolics.

Evidence from numerous observational and clinical studies suggest that polyphenolic phytochemicals such as phenolic acids in olive oil, flavonols in tea, chocolate and grapes, and isoflavones in soy products reduce the risk of breast cancer. A dietary food pattern naturally rich in polyphenols is the Mediterranean diet and evidence suggests those of Mediterranean descent have a lower breast cancer incidence. Whilst dietary polyphenols have been the subject of breast cancer risk-reduction, this review will focus on the clinical effects of polyphenols on reducing recurrence. Overall, we recommend breast cancer patients consume a diet naturally high in flavonol polyphenols including tea, vegetables (onion, broccoli), and fruit (apples, citrus). At least five servings of vegetables and fruit daily appear protective. Moderate soy protein consumption (5–10 g daily) and the Mediterranean dietary pattern show the most promise for breast cancer patients. In this review, we present an overview of clinical trials on supplementary polyphenols of dietary patterns rich in polyphenols on breast cancer recurrence, mechanistic data, and novel delivery systems currently being researched.

Effects of flavonol-rich green tea cultivar (Camellia sinensis L.) on plasma oxidized LDL levels in hypercholesterolemic mice.

To examine the possible benefits of tea flavonols, we compared anti-atherogenic effects between common and flavonol-rich tea cultivars. The tea infusion made from a flavonol-rich cultivar, but not a common cultivar, significantly decreased the plasma oxidized low-density lipoprotein level in mice fed a high-cholesterol diet. The result suggests that tea flavonols have the potential to protect against cardiovascular diseases.

Genetic Variation of Flavonols Quercetin, Myricetin, and Kaempferol in the Sri Lankan Tea (Camellia sinensis L.) and Their Health-Promoting Aspects.

Flavonol glycosides in tea leaves have been quantified as aglycones, quercetin, myricetin, and kaempferol. Occurrence of the said compounds was reported in fruits and vegetable for a long time in association with the antioxidant potential. However, data on flavonols in tea were scanty and, hence, this study aims to envisage the flavonol content in a representative pool of accessions present in the Sri Lankan tea germplasm. Significant amounts of myricetin, quercetin, and kaempferol have been detected in the beverage type tea accessions of the Sri Lankan tea germplasm. This study also revealed that tea is a good source of flavonol glycosides. The Camellia sinensis var. sinensis showed higher content of myricetin, quercetin, and total flavonols than var. assamica and ssp. lasiocalyx. Therefore flavonols and their glycosides can potentially be used in chemotaxonomic studies of tea germplasm. The nonbeverage type cultivars, especially Camellia rosaflora and Camellia japonica Red along with the exotic accessions resembling China type, could be useful in future germplasm studies because they are rich sources of flavonols, namely, quercetin and kaempferol, which are potent antioxidants. The flavonol profiles can be effectively used in choosing parents in tea breeding programmes to generate progenies with a wide range of flavonol glycosides.

Synergistic, antagonistic and additive interactions of green tea polyphenols

Green tea is a natural source of polyphenols where their catechins and flavonols are the major components. Their antioxidant activities are the most important biological effect and often the object of study. DPPH (2,2-diphenyl-1-picryl-hydrazyl) radical assay has been carried out to measure the individual scavenging activities expressed as percentage of DPPH inhibition for each tea polyphenol, and (−)-gallocatechin gallate (GCG) (74.04 ± 0.38 %) and (−)-epigallocatechin gallate (EGCG) (69.51 ± 0.27 %) were the most active compounds. Synergistic, antagonistic and additive interactions among catechin derivatives as well as combined with green tea extract have been analyzed, where GCG and EGCG provided most of the synergistic effects. Flavonols such as quercetin (54.61 ± 0.21 %) and kaempferol (24.06 ± 0.02 %) also showed free radicals’ scavenging activity. Interactions between flavonols and individual catechins as well as their mixtures in the tea extract have been investigated. The results suggested that the presence of tea flavonols in tea extract provided additive interactions and the tea catechins were responsible for synergism in green tea. This work can be the starting point of the research about supplemented green tea from its own catechins to increase the total antioxidant capacity of the green tea.

Epigallocatechin‐3‐gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans

Trisomy for human chromosome 21 results in Down syndrome (DS), which is among the most complex genetic perturbations leading to intellectual disability. Accumulating data suggest that overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), is a critical pathogenic mechanisms in the intellectual deficit. Here we show that the green tea flavonol epigallocatechin-gallate (EGCG), a DYRK1A inhibitor, rescues the cognitive deficits of both segmental trisomy 16 (Ts65Dn) and transgenic mice overexpressing Dyrk1A in a trisomic or disomic genetic background, respectively. It also significantly reverses cognitive deficits in a pilot study in DS individuals with effects on memory recognition, working memory and quality of life. We used the mouse models to ensure that EGCG was able to reduce DYRK1A kinase activity in the hippocampus and found that it also induced significant changes in plasma homocysteine levels, which were correlated with Dyrk1A expression levels. Thus, we could use plasma homocysteine levels as an efficacy biomarker in our human study. We conclude that EGCG is a promising therapeutic tool for cognitive enhancement in DS, and its efficacy may depend of Dyrk1A inhibition.

Bioaccessibility of green tea polyphenols incorporated into an edible agar film during simulated human digestion

Simple edible films can be manufactured to meet not only their primary protective purpose but can be easily manipulated to meet sensory expectations and to contain compounds which enhance the protective properties or even have the potential to deliver health benefits. However, the use of such edible films not only to protect the food but as a vehicle to deliver health benefits has not been investigated. In this paper we study agar films containing an aqueous extract of green tea, rich in polyphenol compounds, and the bioaccessibility of these compounds during simulated digestion in the upper gastro-intestinal tract using a dynamic gastric model (DGM) and a static duodenal model. It is concluded that the recovery of the tea compounds added to the agar film mainly occurs in the stomach (50–80%) and that little or no additional recovery is observed in the duodenum. Furthermore, the green tea compounds recovered show both reducing power and radical scavenging ability, but not antimicrobial activity. The bioaccessibility of the green tea flavonols is reduced in the presence of gelatin used to simulate the presence of protein in the stomach, but it is not clear if this is due to reduced release or sequestration of released compounds by the gelatin.

Green tea flavonols inhibit glucosidase II

Green tea is getting into the focus of scientific interest due to its beneficial health effects, most of which are attributed to its catechin content. Polyphenolic tea catechins have antioxidant, antiproliferative, antiangiogenic and proapoptotic effects, which makes them promising anticancer compounds. Other poly-hydroxy molecules have similar antitumor potentials through the inhibition of glucosidase II, which affects the glycoprotein maturation and quality control in the endoplasmic reticulum. We investigated the effect of tea catechins on glucosidase II activity in rat liver microsomes using 4-methylumbelliferyl glucoside and 4-nitrophenyl glucoside as substrates. A concentration-dependent inhibition with non-competitive kinetics was found. The IC 50 and K i values for certain tea catechins were comparable with those of N-butyldeoxynojirimycin, the widely used glucosidase inhibitor. The possible interference of tea catechins with the glycoprotein processing in the endoplasmic reticulum should be considered as a potential mechanism of their dietary or pharmacological effects.

Enhancement of Interleukin-2 Production in CCRF-CEM, Human T-Cell Leukemia, by Tea Flavonols

Human T-cell leukemia, CCRF-CEM, produced interleukin (IL)-2 stimulated with phorbol myristate acetate (PMA) and pokeweed mitogen (PWM). In PMA/PWM stimulation, IL-2 production in CCRF-CEM was increased by treatment with kaempferol or quercetin, tea (Camellia sinensis L.) flavonols. In this study, we concluded that (1) flavonols affected the expression of CCRF-CEM surface molecules, (2) CCRF-CEM was activated by flavonols, achieving a state receptive to stimulation, and (3) IL-2 production and mRNA expression were promoted by flavonols.

Determination of flavonols in green and black tea leaves and green tea infusions by high-performance liquid chromatography

Tea flavonols are potent antioxidants and make up 2–3% of the water-soluble solids from tea leaves. In this paper, the conditions necessary for hydrolysing and analysing flavonols in tea leaves and tea infusions are optimised and an isocratic elution system for the determination of the hydrolysed flavonols by high-performance liquid chromotography is presented. Aqueous ethanol was selected as the best solution for hydrolysing flavonoids in tea leaves. The contents of flavonols on a dry weight base in green tea leaves ranged from 0.83–1.59, 1.79–4.05, and 1.56–3.31 g/kg, and in black tea leaves from 0.24–0.52, 1.04–3.03, and 1.72–2.31 g/kg for myricetin, quercetin, and kaempferol, respectively. It was observed that the particle size of ground tea leaves significantly influenced the yield of flavonols. The contents of flavonols in different green tea infusions are given.

Differential modulation of the genotoxicity of food carcinogens by naturally occurring monomeric and dimeric polyphenolics

Naturally occurring dimeric polyphenolics and their gallate esters were isolated from grape seeds, almond fruits, and apple skin, and their ability to modulate the mutagenicity of food carcinogens was studied in the Ames test, and compared to that of the monomeric green tea flavonols, (+)-catechin and (−)-epicatechin. Neither the monomeric nor the dimeric polyphenols and their galloylated derivatives influenced the mutagenic activity elicited by the indirectly acting food carcinogens benzo[a]pyrene and 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), in the presence of a hepatic activation system derived from Aroclor 1254–treated rats; the only exception was the B7 dimer, which, at concentrations above 1 μM, suppressed the mutagenicity of IQ. None of the polyphenolics modulated the mutagenic activity elicited by the directly acting carcinogen N′-methyl-N′-nitro-nitrosoguanidine (MNNG). In contrast, all the dimeric polyphenols and the galloylated metabolites, at concentrations over 1 μM, potentiated the mutagenic activity induced by the indirectly acting carcinogen N-nitrosopyrrolidine, in the presence of an activation system derived from isoniazid-treated rats. In conclusion, dimeric polyphenols and galloylated derivatives of plant origin are unlikely to influence the initiation stage of the carcinogenicity of chemicals through mechanisms that involve inhibition of their cytochrome P450–mediated bioactivation or scavenging of the reactive, genotoxic intermediates. Environ. Mol. Mutagen. 35:86–98, 2000 © 2000 Wiley-Liss, Inc.

Differential modulation of the genotoxicity of food carcinogens by naturally occurring monomeric and dimeric polyphenolics

Naturally occurring dimeric polyphenolics and their gallate esters were isolated from grape seeds, almond fruits, and apple skin, and their ability to modulate the mutagenicity of food carcinogens was studied in the Ames test, and compared to that of the monomeric green tea flavonols, (+)-catechin and (-)-epicatechin. Neither the monomeric nor the dimeric polyphenols and their galloylated derivatives influenced the mutagenic activity elicited by the indirectly acting food carcinogens benzo[a]pyrene and 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), in the presence of a hepatic activation system derived from Aroclor 1254-treated rats; the only exception was the B7 dimer, which, at concentrations above 1 microM, suppressed the mutagenicity of IQ. None of the polyphenolics modulated the mutagenic activity elicited by the directly acting carcinogen N'-methyl-N'-nitro-nitrosoguanidine (MNNG). In contrast, all the dimeric polyphenols and the galloylated metabolites, at concentrations over 1 microM, potentiated the mutagenic activity induced by the indirectly acting carcinogen N-nitrosopyrrolidine, in the presence of an activation system derived from isoniazid-treated rats. In conclusion, dimeric polyphenols and galloylated derivatives of plant origin are unlikely to influence the initiation stage of the carcinogenicity of chemicals through mechanisms that involve inhibition of their cytochrome P450-mediated bioactivation or scavenging of the reactive, genotoxic intermediates.

Effects of tea polyphenols on the invasion and matrix metalloproteinases activities of human fibrosarcoma HT1080 cells.

The effects of tea polyphenols on the invasion of highly metastatic human fibrosarcoma HT1080 cells through a monolayer of human umbilical vein endothelial cells (HUVECs) and the accompanying basal membrane were investigated. Among the tea polyphenols tested, epicatechin gallate (ECg), epigallocatechin gallate (EGCg), and theaflavin strongly suppressed the invasion of HT1080 cells into the monolayer of HUVECs/gelatin membrane, whereas epicatechin, epigallocatechin, tea flavonols, tea flavones, and gallate derivatives had no effect. Both theaflavin-digallate and theasinensin D showed a weak invasion inhibitory effect. ECg significantly inhibited the invasion without cytotoxicity against cancer cells and HUVECs. Ester-type catechins (ECg and EGCg) and theaflavin strongly suppressed the gelatin degradation mediated by matrix metalloproteinase (MMP) 2 and MMP-9, which were secreted into the conditioned medium of HT1080 cells. In conclusion, among the tea polyphenols tested, ECg was considered to be the agent with the most potential antimetastasis activity because it inhibited invasion in the absence of cytotoxicity.

Tea flavonols in cardiovascular disease and cancer epidemiology.

Tea is an important dietary source of flavonols in countries such as the Netherlands, the United Kingdom and Japan. Flavonols may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumor development in animal studies. The association between flavonol intake and cancer risk was investigated in three prospective studies (Zutphen Elderly Study in the Netherlands, a Finnish cohort, and the Netherlands Cohort Study). Only one study (Finnish cohort) showed an inverse association with cancer mortality. The intake of flavonols with subsequent cardiovascular disease was studied in six prospective epidemiological studies. In some populations (Seven Countries Study, Zutphen Elderly Study, a Finnish cohort) a clear protective effect was observed. In a large US cohort, a protective effect was only found in a subgroup with previous history of coronary heart disease, whereas in Welsh men, flavonol intake, mainly from tea, was associated with an increased risk of coronary heart disease. These conflicting results may be due to confounding by coronary risk factors associated with tea consumption. The question of whether flavonols protect against cardiovascular disease remains still open; a protective effect of flavonols against cancer is less likely.

Tea Flavonols in Cardiovascular Disease and Cancer Epidemiology

Tea is an important dietary source of flavonols in countries such as the Netherlands, the United Kingdom and Japan. Flavonols may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumor development in animal studies. The association between flavonol intake and cancer risk was investigated in three prospective studies (Zutphen Elderly Study in the Netherlands, a Finnish cohort, and the Netherlands Cohort Study). Only one study (Finnish cohort) showed an inverse association with cancer mortality. The intake of flavonols with subsequent cardiovascular disease was studied in six prospective epidemiological studies. In some populations (Seven Countries Study, Zutphen Elderly Study, a Finnish cohort) a clear protective effect was observed. In a large US cohort, a protective effect was only found in a subgroup with previous history of coronary heart disease, whereas in Welsh men, flavonol intake, mainly from tea, was associated with an increased risk of coronary heart disease. These conflicting results may be due to confounding by coronary risk factors associated with tea consumption. The question of whether flavonols protect against cardiovascular disease remains still open; a protective effect of flavonols against cancer is less likely.