Dose Of Epigallocatechin-3-gallate Research Articles

Assessment of the Impact of Dietary Supplementation with Epigallocatechin Gallate (EGCG) on Antioxidant Status, Immune Response, and Intestinal Microbiota in Post-Weaning Rabbits.

This study was conducted to investigate the impact of EGCG on antioxidant stress, immune response, and intestinal microbiota flora in post-weaning rabbits. A total of 144 40 d Ira rabbits (equally divided by sex), were randomly allocated to six treatments. with five groups receiving doses of 200, 400, 600, 800, and 1000 mg/kg of EGCG, while one group served as a control without EGCG. Over 48 days, this study the assessed growth performance, antioxidant capacity, immune system, intestinal morphology, and cecal microbiota in the rabbits. The results showed that EGCG did not affect growth performance; however, significant linear and quadratic correlations were observed between the MDA, T-AOC, and GSH-Px activities in the liver and jejunum (p < 0.05). Quadratic effects were observed for the spleen and thymus indexes and serum IgG levels with increasing EGCG dosages (p < 0.05). Additionally, positive linear and quadratic effects were found on the ileal villus height and the villus height/crypt depth ratio. The relative abundances of Euryarchaeota, Patescibacteria, and Synergistota were significantly enriched in rabbits fed with high dosages (600-1000 mg/kg) of EGCG. Conclusively, the addition of large doses of EGCG (400-800 mg/kg) can effectively suppress oxidative stress and alleviate weaning stress, thereby contributing to the protection of post-weaning rabbits.

Protective Effect of Epigallocatechin-3-gallate against Hepatic Oxidative Stress Induced by tert-Butyl Hhydroperoxide in Yellow-Feathered Broilers.

Recent studies have shown that epigallocatechin-3-gallate (EGCG), as an effective antioxidant, could attenuate the oxidative damage, inflammation and necrosis in the liver in response to oxidative stress. The present study investigated whether oral administration of EGCG could effectively alleviate the hepatic histopathological changes and oxidative damage in yellow-feathered broilers induced by tert-butyl hydroperoxide (t-BHP). Broilers were exposed to 600 μmol t-BHP/kg body weight (BW) to induce oxidative stress by intraperitoneal injection every five days, followed by oral administration of different doses of EGCG (0, 20, 40 and 60 mg/kg BW) and 20 mg vitamin E (VE)/kg BW every day during 5-21 days of age. The results showed that t-BHP injection decreased (p < 0.05) body weight and the relative weight of the spleen; the enzyme activities of total antioxidant capacity (T-AOC), catalase (CAT) and total superoxide dismutase (SOD); and gene mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), CAT, SOD1, SOD2 and acetyl-CoA carboxylase (ACACA); as well as increased (p < 0.05) necrosis formation, malondialdehyde (MDA) content, reactive oxygen species (ROS)accumulation, and peroxisome proliferator activates receptor-α (PPARα) mRNA expression in the liver of yellow-feathered female broilers at 21 days of age. Treatment with 60 mg EGCG/kg BW orally could enhance antioxidant enzyme activities and reverse the hepatic damage induced by t-BHP injection by reducing the accumulation of ROS and MDA in the liver and activating the Nrf2 and PPARα pathways related to the induction of antioxidant gene expression (p < 0.05). In conclusion, intraperitoneal injection of t-BHP impaired body growth and induced hepatic ROS accumulation, which destroyed the antioxidant system and led to oxidative damage in the liver of yellow-feathered broilers from 5 to 21 days of age. It is suggested that EGCG may play an antioxidant role through the Nrf2 and PPARα signaling pathways to effectively protect against t-BHP-induced hepatic oxidative damage in broilers, and the appropriate dose was 60 mg EGCG/kg BW by oral administration.

Polyphenol (−)-Epigallocatechin Gallate (EGCG) mitigated kidney injury by regulating metabolic homeostasis and mitochondrial dynamics involvement with Drp1-mediated mitochondrial fission in mice

The study aimed to examine effects of (−)-epigallocatechin-3-gallate (EGCG) on energy metabolism and mitochondrial dynamics in mouse model of renal injury caused by doxorubicin (DOX). Here, mice were divided into Control group, EGCG-only treated group, DOX group, and three doses of EGCG plus DOX groups. Our results showed that EGCG behaved beneficial effects against kidney injury via attenuation of pathological changes in kidney tissue, which was confirmed by reducing serum creatinine (SCr), blood urea nitrogen (BUN), and apoptosis. Subsequently, changes in reactive oxygen species generation, malondialdehyde content, and activities of antioxidant enzymes were considerably ameliorated in EGCG + DOX groups when compared to DOX group. Furthermore, EGCG-evoked renal protection was associated with increases of mitochondrial membrane potential and decreases of mitochondrial fission protein Dynamin-related protein 1 (Drp1). Moreover, changing glycolysis into mitochondrial oxidative phosphorylation was observed, evidenced by controlling activities of malate dehydrogenase (MDH) and hexokinase (HK) in EGCG + DOX groups when compared to DOX group, indicating that reprogramming energy metabolism was linked to EGCG-induced renal protection in mice. Therefore, EGCG was demonstrated to have a protective effect against kidney injury by reducing oxidative damage, metabolic disorders, and mitochondrial dysfunction, suggesting that EGCG has potential as a feasible strategy to prevent kidney injury.

Effect of Epigallocatechin Gallate on the Inflammatory Response in Mice (Mus musculus) Kidneys

Background: Epigallocatechin gallate is the primary polyphenol constituent of green tea. It has the ability to inhibit the pathological processes caused by oxidants. However, in certain cases, the green tea diet is known to exert pro-oxidant effects. In addition, studies have shown that epigallocatechin gallate negatively affects cells. Several studies on epigallocatechin gallate showed increased oxidative stress and decreased intracellular antioxidants. Furthermore, it can stimulate an inflammatory response from the innate immune system, which may contribute to the elimination of the effects of epigallocatechin gallate. Purpose: This study aims to investigate the inflammatory responses (IL-1, IL-6, and TNF-α) in mice kidneys due to epigallocatechin gallate. Methods: This study involved the use of experimental animals aged between two and three months with an average body weight of 20 grams. The animals were randomly divided into two groups, namely the control group and the epigallocatechin gallate treatment group, with each group consisting of 16 samples. The dose of epigallocatechin gallate used in this study was 750 mg/kg bw. The treatment was administered for three days, after which the kidneys were collected. Immunohistochemical staining was used to observe the inflammatory response, including IL-1, IL-6 and TNF-α. Subsequently, all the data were collected and statistically analyzed using an independent t-test. Results: The results of the data analysis showed a significant difference in the expression of IL-6 (p = 0.018) and TNF-α (p = 0.000), but no significant difference in the expression of IL-1 (p = 0.106). Conclusion: In conclusion, epigallocatechin gallate was found to induce an inflammatory response in mice kidneys.

Amelioration of Functional, Metabolic, and Morphological Deterioration in the Retina following Retinal Detachment by Green Tea Extract.

Retinal detachment (RD) can result in the loss of photoreceptors that cause vision impairment and potential blindness. This study explores the protective effects of the oral administration of green tea extract (GTE) in a rat model of RD. Various doses of GTE or epigallocatechin gallate (EGCG), the most active ingredient in green tea catechins, were administered to Sprague Dawley (SD) rats with experimentally induced retinal detachment. The rats received sub-retinal injections of hyaluronic acid (0.1%) to induce RD and were given different doses of GTE and EGCG twice daily for three days. Notably, a low dose of GTE (142.9 mg/kg) caused significantly higher signal amplitudes in electroretinograms (ERGs) compared to higher GTE doses and any doses of EGCG. After administration of a low dose of GTE, the outer nuclear layer thickness, following normalization, of the detached retina reduced to 82.4 ± 8.2% (Mean ± SEM, p < 0.05) of the thickness by RD treatment. This thickness was similar to non-RD conditions, at 83.5 ± 4.7% (Mean ± SEM) of the thickness following RD treatment. In addition, the number of TUNEL-positive cells decreased from 76.7 ± 7.4 to 4.7 ± 1.02 (Mean ± SEM, p < 0.0001). This reduction was associated with the inhibition of apoptosis through decreased sphingomyelin levels and mitigation of oxidative stress shown by a lowered protein carbonyl level, which may involve suppression of HIF-1α pathways. Furthermore, GTE showed anti-inflammatory effects by reducing inflammatory cytokines and increasing resolving cytokines. In conclusion, low-dose GTE, but not EGCG, significantly alleviated RD-induced apoptosis, oxidative stress, inflammation, and energy insufficiency within a short period and without affecting energy metabolism. These findings suggest the potential of low-dose GTE as a protective agent for the retina in RD.

Gallation and B-Ring Dihydroxylation Increase Green Tea Catechin Residence Time in Plasma by Differentially Affecting Tissue-Specific Trafficking: Compartmental Model of Catechin Kinetics in Healthy Adults.

Catechins in green tea extract (GTE) (epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), epicatechin gallate (ECG)) vary in bioactivity. We developed a physiologically relevant mathematical model of catechin metabolism to test the hypothesis that fractional catabolic rates of catechins would be differentially affected by their structural attributes. Pharmacokinetic data of plasma and urine catechin concentrations were used from healthy adults (n = 19) who ingested confections containing 0.5 g GTE (290 mg EGCG, 87 mg EGC, 39 mg EC, 28 mg ECG). A 7-compartmental model of catechin metabolism comprised of the gastrointestinal tract (stomach, small and large intestine), liver, plasma, extravascular tissues, and kidneys was developed using a mean fraction dose of EGCG, ECG, EGC, and EC. Fitting was by iterative least squares regression analysis, and goodness of fit was ascertained by the estimated variability of parameters (FSD < 0.5). The interaction of gallation and B-ring dihydroxylation most greatly extended plasma residence time such that EGC > EC = EGCG > EGC. The interaction between gallation and B-ring dihydroxylation accelerated the transfer from the upper gastrointestinal tract to the small intestine but delayed subsequent transfers from the small intestine through the liver to plasma and from kidneys to urine. Gallation and B-ring dihydroxylation independently delayed the transfer from plasma to extravascular tissues, except the uptake to kidneys, which was slowed by gallation only. This multi-compartment model, to be validated in a future study, suggests that gallation and B-ring dihydroxylation affect catechin catabolism in a tissue-specific manner and thus their potential bioactivity.

Suppression mechanism of L-lysine on the Epigallocatechin-3-gallate-induced loss of myofibrillar protein gelling potential

As a natural antioxidant, Epigallocatechin-3-gallate (EGCG) needed to be added in high doses to maintain the quality of meat products. However, high doses of EGCG caused the excessive aggregation of myofibrillar protein (MP), which damaged the gel properties of MP gels. Therefore, the purpose of this study was to investigate the mitigation of EGCG-induced loss of MP gelling potential by L-Lysine (L-Lys). The results showed that the addition of 20 mM L-Lys induced excessive unfolding and loose aggregation of MP at 10 µmol/g EGCG, and hence, reducing the solubility (14.5%) and the tryptophan fluorescence, and forming a network structure with a large aperture. Therefore, the cooking loss was decreased from 29.20% to 15.13%, and the strength of MP gels was decreased from 0.35 N to 0.17 N. However, L-Lys hindered the hydrogen bonding interactions and hydrophobic interactions between MP and EGCG by competing the binding sites of MP at 50 µmol/g EGCG, which was supported by the Zeta potential, surface hydrophobicity, FTIR and molecular docking analysis. Thus L-Lys mitigated the protein aggregation caused by 50 µmol/g EGCG, improved the solubility (23.02%∼86.99%) and apparent viscosity, which were beneficial for the formation of a continuous network structure in MP gels. Therefore, the cooking loss of MP gels was decreased from 52.40% to 41.30%, and the gel strength was enhanced from 0.13 N to o.22 N with 20 mM L-Lys addition. The present study could provide a new strategy for increasing the amounts of EGCG in meat products without damaging the gel properties of meat products.

Effect of epigallocatechin gallate in green tea on preventing lens opacity and αB-crystallin aggregation in rat model of diabetes.

To evaluate the effect of epigallocatechin gallate (EGCG) in preventing lens opacity and the aggregation of lens αB-crystallin in model rats of diabetes mellitus (DM). This experimental study included Wistar rats for DM as in vivo models and divided into 5 groups. The treatment groups were administered EGCG by orally for 20d and were then assessed for their degree of lens opacity with binocular microscope and lens αB-crystallin expression from Western blot analyze. Pearson correlation test and regression analysis on EGCG exposure and final random blood sugar (RBS) obtained a significance level of P<0.05. EGCG exposure can significantly lower RBS with an R 2 of 0.5634 (56.34%). The same analysis on EGCG exposure and the degree of lens opacity obtained a significance level of P<0.05 and increased exposure to EGCG can significantly lower the degree of lens opacity with an R 2 of 0.8577 (85.77%). Correlation analysis between EGCG and the expression of lens αB-crystallin can be concluded that the higher the EGCG exposure administered, the higher the native lens αB-crystallin expression and the lower the aggregate lens αB-crystallin expression. There was also significant effect in which every 1 mg/kg body weight dose of EGCG can increase the native lens αB-crystallin expression by 0.0063 and decrease the aggregate lens αB-crystallin expression by 0.0076. The administration of EGCG at a dose of 300, 600, and 1200 mg shows a significant effect on preventing lens opacity and aggregation of αB-crystallin in diabetic rat models and this research could be a biomolecular prevention of cataract.

Comparative urine metabolomics of mice treated with non-toxic and toxic oral doses of (-)-epigallocatechin-3-gallate.

The green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), has been studied for its potential positive health effects, but human and animal model studies have reported potential toxicity at high oral bolus doses. This study used liquid chromatography-mass spectrometry-based metabolomics to compare the urinary EGCG metabolite profile after administration of a single non-toxic (100 mg kg-1) or toxic (750 mg kg-1) oral bolus dose to male C57BL6/J mice to better understand how EGCG metabolism varies with dose. EGCG metabolites, including methyl, glucuronide, sulfate, and glucoside conjugates, were tentatively identified based on their mass to charge (m/z) ratio and fragment ion patterns. Partial least squares discriminant analysis (PLS-DA) results showed clear separation of the urine metabolite profiles between treatment groups. The most differentiating metabolites in the negative and positive ion modes were provisionally identified as di-glucuronidated EGCG quinone and di-glucuronidated EGCG, respectively. The presence of EGCG oxidation products at toxic dose is consistent with studies showing that EGCG toxicity is associated with oxidative stress. Relative amounts of methylated metabolites increased with dose to a lesser extent than glucuronide and sulfate metabolites, indicating that methylation is more prominent at low doses, whereas glucuronidation and sulfation may be more important at higher doses. One limitation of the current work is that the lack of commercially-available EGCG metabolite standards prevented absolute metabolite quantification and identification. Despite this limitation, these findings provide a basis for better understanding the dose-dependent changes in EGCG metabolism and advance studies on how these differences may contribute to the toxicity of high doses of EGCG.

Physicochemical Properties and Oxidative Stability of an Emulsion Prepared from (-)-Epigallocatechin-3-Gallate Modified Chicken Wooden Breast Myofibrillar Protein.

The deterioration of wooden breast myofibrillar protein (WBMP) causes a decline in its processing performance, and the protein becomes easier to oxidize. Previous studies have revealed that the use of (-)-epigallocatechin-3-gallate (EGCG) may improve the physicochemical properties and oxidative stability of proteins in aqueous solutions. The effects of varying concentrations (0.01%, 0.02%, 0.03%, and 0.04% w/v) of EGCG on the physicochemical properties of a WBMP emulsion (1.2% WBMP/10% oil) and the inhibition of lipid and protein oxidation were studied. The results revealed that a moderate dose of EGCG (0.03%) could significantly (p &lt; 0.05) improve the emulsion activity index (4.66 ± 0.41 m2/g) and emulsion stability index (91.95 ± 4.23%), as well as reduce the particle size of the WBMP emulsion. According to the micrographs and cream index, 0.03% EGCG retarded the phase separation by stopping the aggregation of droplets and proteins, thus significantly improving the stability of WBMP emulsions. During storage at 50 °C for 96 h, 0.03% EGCG inhibited lipid oxidation (lipid hydroperoxide and 2-thiobarbituric acid-reactive substance formation) and protein oxidation (carbonyl formation and sulfhydryl loss). In contrast, lower and higher EGCG concentrations (0.01%, 0.02%, and 0.04%) demonstrated shortcomings (such as weak antioxidant capacity or protein over-aggregation) in improving the quality and oxidation stability of the emulsion. In conclusion, a moderate dose of EGCG (0.03%) can be used to improve the quality and shelf life of WBMP emulsions.

Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation in Attenuating Hypertension via Its Modulatory Activities on the Intrarenal Renin-Angiotensin System in Spontaneously Hypertensive Rats.

This study aimed to identify the no-observed-adverse-effect level (NOAEL) of dietary epigallocatechin gallate (EGCG) supplementation and its possible antihypertensive and nutrigenomics effects in modulating intrarenal renin-angiotensin system (RAS) gene expression in spontaneously hypertensive rats (SHR). EGCG (50, 250, 500 or 1000 mg/kg b.w. i.g., once daily) was administered to SHR for 28 days. All the SHR survived with no signs of systemic toxicity. Increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and thiobarbituric acid reactive substances (TBARS) were evident in SHR supplemented with 500 and 1000 mg/kg b.w. but not in those supplemented with lower doses of EGCG. Subsequently, the NOAEL of EGCG was established at 250 mg/kg b.w., and the same protocol was replicated to assess its effects on blood pressure and renal RAS-related genes in SHR. The systolic blood pressure (SBP) of the EGCG group was consistently lower than the control group. The mRNA levels of cortical Agtr2 and Ace2 and medullary Agtr2, Ace and Mas1 were upregulated while medullary Ren was downregulated in EGCG group. Statistical analysis showed that SBP reduction was associated with the changes in medullary Agtr2, Ace, and Ren. Dietary EGCG supplementation exhibits antihypertensive and nutrigenomics effects through activation of intrarenal Ace and Agtr2 and suppression of Ren mediators, while a high dose of EGCG induced liver damage in SHR. In future clinical studies, liver damage biomarkers should be closely monitored to further establish the safety of the long-term use of EGCG.

Simultaneous loading of (−)-epigallocatechin gallate and ferulic acid in chitosan-based nanoparticles as effective antioxidant and potential skin-whitening agents

Chitosan (CS) based nanoparticles simultaneously loaded with (−)-epigallocatechin gallate (EGCG) and ferulic acid (FA) were fabricated via ionic gelation method modified by sodium tripolyphosphate and genipin (G-CS-EGCG-FA NPs). The particle size, morphology, entrapment efficiency, rheological properties, antioxidant and tyrosinase inhibitory activity of NPs were investigated. The G-CS-EGCG-FA NPs exhibited irregular ellipsoidal shape with average diameter of 412.3 nm and high DPPH and ABTS·+ scavenging ability. The entrapment efficiency of EGCG and FA in NPs was 46.0 ± 1.3 % and 46.8 ± 1.6 %, respectively. CS-based NPs show no toxic effects on NIH 3 T3 cells and B16-F10 melanoma cells with concentration <200 μg/mL and 25 μg/mL, respectively and the cell viability ranged from 100 % to 118 %. Meanwhile, the oxidative repaired capacity of G-CS-EGCG-FA NPs (200 μg/mL) in H2O2-induced cells was over 100 %, higher than that of the same dose of free EGCG or FA. Moreover, the tyrosinase inhibition activity of G-CS-EGCG-FA NPs (25 μg/mL) (84.6 %) was more potent than that of free EGCG (55.3 %), free FA (47.1 %) and kojic acid, indicating the good skin repairing and whitening ability of G-CS-EGCG-FA NPs. Given these results, this research provides new insights for designing novel particles loaded with dual bioactive agents that possess synergistic benefits.

Epigallocatechin-3-gallate attenuates myocardial fibrosis in diabetic rats by activating autophagy.

Epigallocatechin-3-gallate (EGCG) possesses anti-fibrotic potential in diverse tissues; however, the molecular mechanisms underlying the impacts of EGCG on diabetes-induced myocardial fibrosis remain unclear. This present study aimed to unravel the anti-fibrotic effects of EGCG on the heart in type 2 diabetic rats and investigate its molecular mechanisms. Rats were randomly assigned to the following four groups: Normal (NOR), diabetic cardiomyopathy (DCM), DCM + 40 mg/kg EGCG, and DCM + 80 mg/kg EGCG groups. After 8 weeks of EGCG treatment, fasting blood glucose, left ventricular hemodynamic indices, heart index, and myocardial injury-related parameters were measured. Hematoxylin and eosin staining and Sirius Red staining were used to evaluate myocardial pathological alterations and collagen accumulation. The contents of myocardial hydroxyproline, collagen-I, collagen-III, transforming growth factor (TGF)-β1, matrix metalloprotease (MMP)-2, and MMP-9 were measured. The gene expression levels of myocardial TGF-β1, MMP-2, and MMP-9 were detected. Autophagic regulators, including adenosine 5'-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), and autophagic markers, including microtubule-associated protein-1 light chain 3 and Beclin1 were estimated. The results indicated that diabetes significantly decreased cardiac contractile function and aggravated myocardial hypertrophy and injury. Furthermore, diabetes repressed the activation of autophagy in myocardial tissue and promoted cardiac fibrosis. Following ingestion with different doses of EGCG, myocardial contractile dysfunction, hypertrophy and injury were ameliorated; myocardial autophagy was activated, and myocardial fibrosis was alleviated in the EGCG treatment groups. In conclusion, these findings suggested that EGCG could attenuate cardiac fibrosis in type 2 diabetic rats, and its underlying mechanisms associated with activation of autophagy via modulation of the AMPK/mTOR pathway and then repression of the TGF-β/MMPs pathway.

Aqueous core epigallocatechin gallate PLGA nanocapsules: characterization, antibacterial activity against uropathogens, and in vivo reno-protective effect in cisplatin induced nephrotoxicity

Epigallocatechin-3-gallate (EGCG) was isolated from Cycas thouarsii leaves for the first time and encapsulated in aqueous core poly(lactide-co-glycolide) (PLGA) nanocapsules (NCs). This work investigates antimicrobial activity and in vivo reno-protective effects of EGCG-PLGA NCs in cisplatin-induced nephrotoxicity. A double emulsion solvent evaporation process was adopted to prepare PLGA NCs loaded with EGCG. Particle size, polydispersity index (PDI), zeta potential, percent entrapment efficiency (%EE), structural morphology, and in vitro release platform were all studied in vitro. The optimum formula (F2) with particle size (61.37 ± 5.90 nm), PDI (0.125 ± 0.027), zeta potential (–11.83 ± 3.22 mV), %EE (85.79 ± 5.89%w/w), initial burst (36.85 ± 4.79), and percent cumulative release (87.79 ± 9.84) was selected for further in vitro/in vivo studies. F2 exhibited an enhanced antimicrobial activity against uropathogens as it had lower minimum inhibitory concentration (MIC) values and a more significant impact on bacterial growth than free EGCG. Forty male adult mice were randomly allocated into five groups: control vehicle, untreated methotrexate, MTX groups treated with a daily oral dose of free EGCG, placebo PLGA NCs, and EGCG PLGA NCs (F2) for 10 days. Results showed that EGCG PLGA NCs (F2) exerted promising renoprotective effects compared to free EGCG. EGCG PLGA NCs group induced a significant decrease in kidney index, serum creatinine, kidney injury molecule-1 (KIM-1), NGAL serum levels, and pronounced inhibition of NLPR-3/caspase-1/IL/1β inflammasome pathway. It also significantly ameliorated oxidative stress and decreased NFκB, Bax expression levels. Aqueous core PLGA NCs are a promising formulation strategy that provides high polymeric protection and sustained release pattern for hydrophilic therapeutic agents.

Positive effects of Epigallocatechin-3-gallate (EGCG) intervention on insulin resistance and gut microbial dysbiosis induced by bisphenol A

Schematic illustration of ameliorative effects of EGCG on BPA-induced insulin resistance. • EGCG intervention successfully ameliorated insulin resistance and impaired insulin sensitivity induced by BPA exposure. • EGCG intervention restored serious damage of gut tight junctions. • EGCG effectively improved intestinal flora disorder and increased gut short chain fatty acids level. Bisphenol A (BPA), a plasticizer, is widely believed to cause metabolic disorders. However, an effective intervention is still absent. This study investigated the beneficial effects of Epigallocatechin-3-gallate (EGCG) on insulin resistance and microbial disturbance induced by BPA. The serum glucose, insulin, total triglyceride, and total cholesterol were decreased in BPA-treated mice after the intervention of EGCG. The sensitivity of insulin signals in peripheral tissue was improved by modulating the phosphorylation of IRS-1, Akt, and GSK-3β. In addition, 16S rRNA analysis for fecal microbiota showed the relative abundance of Ruminiclostridium , Blautia , unidentified_Ruminococcaceae , and Candidatus_Saccharimonas were restored by the high dose of EGCG. Furthermore, EGCG increased the concentrations of fecal short-chain fatty acids and protected the gut barrier impaired by BPA. Overall, our results demonstrated the positive effects of EGCG on BPA-induced insulin resistance and gut microbial dysbiosis. The current study provides a potential treatment for the chronic metabolic toxicity of BPA.

Epigallocatechin-3-gallate ameliorates hepatic damages by relieve FGF21 resistance and promotion of FGF21\u2013AMPK pathway in mice fed a high fat diet

BackgroundNon-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Epigallocatechin-3-gallate (EGCG) derived from extract of green tea and is well known for beneficial effects on anti-oxidative, anti-inflammatory, and anti-tumor activity. The present study aimed to implore its underlying mechanism for protective effect of NAFLD.MethodsMice were fed either high fat diet (HFD) or chow diet with or without EGCG treatment in HFD group, for up to 16 weeks. Histopathology, expression of lipid and glucose metabolism and lipogenesis-related gene expression were assessed. Primary mouse hepatocytes were treated with free fatty acids combined with different doses of EGCG for 48 h, expression of lipid and lipogenesis-related gene expression were assessed.ResultsThe results showed that EGCG attenuated HFD- and FFA-induced lipid accumulation in vivo and in vitro. EGCG can decrease the oxidative stress and promote Nrf2 level. Meanwhile EGCG alleviated FGF21 resistance and elevated FGFR/AMPK expression, which suggested an unrecognized mechanism of EGCG in ameliorating NAFLD.ConclusionsEGCG attenuated hepatocytes damage and dysfunction in NAFLD by alleviating FGF21 resistance and improve FGFR/AMPK pathway, mitigating oxidative stress. Our studies verified that EGCG may become a promising drug to treat or relieve NAFLD.

Increased dosage and treatment time of Epigallocatechin-3-gallate (EGCG) negatively affects skeletal parameters in normal mice and Down syndrome mouse models.

Bone abnormalities affect all individuals with Down syndrome (DS) and are linked to abnormal expression of DYRK1A, a gene found in three copies in people with DS and Ts65Dn DS model mice. Previous work in Ts65Dn male mice demonstrated that both genetic normalization of Dyrk1a and treatment with ~9 mg/kg/day Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea and putative DYRK1A inhibitor, improved some skeletal deficits. Because EGCG treatment improved mostly trabecular skeletal deficits, we hypothesized that increasing EGCG treatment dosage and length of administration would positively affect both trabecular and cortical bone in Ts65Dn mice. Treatment of individuals with DS with green tea extract (GTE) containing EGCG also showed some weight loss in individuals with DS, and we hypothesized that weights would be affected in Ts65Dn mice after EGCG treatment. Treatment with ~20 mg/kg/day EGCG for seven weeks showed no improvements in male Ts65Dn trabecular bone and only limited improvements in cortical measures. Comparing skeletal analyses after ~20mg/kg/day EGCG treatment with previously published treatments with ~9, 50, and 200 mg/kg/day EGCG showed that increased dosage and treatment time increased cortical structural deficits leading to weaker appendicular bones in male mice. Weight was not affected by treatment in mice, except for those given a high dose of EGCG by oral gavage. These data indicate that high doses of EGCG, similar to those reported in some treatment studies of DS and other disorders, may impair long bone structure and strength. Skeletal phenotypes should be monitored when high doses of EGCG are administered therapeutically.

Effects of the psychoactive compounds in green tea on risky decision-making.

Epigallocatechin-3-gallate (EGCG) and caffeine are the two primary compounds found in green tea. While EGCG has anxiolytic and anti-inflammatory effects, its acute effects on cognition are not well understood. Furthermore, despite widespread green tea consumption, little is known about how EGCG and caffeine co-administration impacts behavior. Here, we investigated the effects of multiple doses of either EGCG or caffeine on a rat model of risk-taking. This was assessed using the risky decision-making task (RDT), in which rats choose between a small, well-tolerated reward and a large reward with escalating risk of mild footshock. Rats were tested in RDT after acute systemic administration of EGCG, caffeine or joint EGCG and caffeine. EGCG caused a dose-dependent reduction in risk-taking without affecting reward discrimination or task engagement. Caffeine did not impact risk-taking, but elevated locomotor activity and reduced task engagement at high doses. Finally, exposure to both EGCG and caffeine had no effect on risk-taking, suggesting that low-dose caffeine is sufficient to mask the risk-aversion caused by EGCG. These data suggest EGCG as a potential therapeutic treatment for psychological disorders that induce compulsive risky decision-making.

Epigallocatechin gallate and theaflavins independently alleviate cyclophosphamide-induced ovarian damage by inhibiting the overactivation of primordial follicles and follicular atresia

BackgroundCyclophosphamide (CTX), which has been used to treat common female cancers for several years, often causes ovarian damage, early menopause and infertility. However, strategies for the effective prevention and treatment of CTX-induced ovarian damage are still lacking. Epigallocatechin gallate (EGCG) and theaflavins (TFs), key molecules derived from green tea or black tea, have been shown to exert preventive effects on many ageing-related diseases. PurposeWe aimed to explore the potential preventive and protective effects of EGCG and TFs on CTX-induced ovarian damage and compare the two compounds. Study DesignSix-week-old female mice were administered a low or high dose of EGCG or TFs. The low dose was equivalent to the average daily amount of tea consumed by a drinker. MethodsWe determined the oestrous cycle and serum hormone levels to evaluate ovarian endocrine function, and we performed mating tests for reproductivity. We also assessed the follicle count and AMH level to evaluate ovarian reserve, and we performed Masson's trichrome and Sirius red staining to evaluate ovarian fibrosis. We conducted γ-H2AX and TUNEL analyses to evaluate DNA damage, and we also measured the relevant indicators of oxidative stress and follicular activation, including NRF2, HO-1, SOD2, AKT, mTOR and RPS6. ResultsEGCG and TFs treatment independently improved the ovarian endocrine function and reproductivity of mice that were administered CTX. EGCG and TFs also increased the ovarian reserve of these animals. Furthermore, EGCG and TFs alleviated oxidation-induced damage to ovarian DNA in mice by activating the NRF2/HO-1 and SOD2 pathways and reducing the apoptosis of growing follicles. At the same time, EGCG and TFs reduced the overactivation of primordial follicles by inhibiting the AKT/mTOR/RPS6 pathway. ConclusionThe present study showed that EGCG and TFs independently improved ovarian function in mice with CTX-induced ovarian damage, thereby providing useful information for designing a potential clinical strategy that will protect against chemotherapy-induced ovarian damage.

Oral epigallocatechin gallate reduces intestinal nadolol absorption via modulation of Oatp1a5 and Oct1 transcriptional levels in spontaneously hypertensive rats

BackgroundConcurrent use of epigallocatechin-3-gallate (EGCG) and medication may lead to botanical-drug interactions, subsequently therapeutic failure or drug toxicity. It has been reported that EGCG reduces plasma nadolol bioavailability in normotensive models. Nevertheless, evidence on the effects of EGCG on hypertensive model, and the possible underlying mechanism have not been elucidated. ObjectivesThis study aims (i) to investigate the effects of EGCG on nadolol pharmacokinetics (maximum plasma concentration, time to achieve maximum concentration, area under the time-plasma concentration curve, plasma half-life and total clearance) and subsequently its impact on blood pressure control; and (ii) to identify transcriptional regulatory roles of EGCG on the nadolol intestinal and hepatic drug-transporters in SHR. MethodsMale SHR were pre-treated with a daily dose of EGCG (10 mg/kg body weight, i.g.) for 13 days. On day-14, a single dose of nadolol (10 mg/kg body weight) was given to the rats 30 min after the last dose of EGCG administration. Systolic blood pressure (SBP) was measured at 6-h and 22-h post-nadolol administration. Plasma and urinary nadolol concentrations were quantified using high-performance liquid chromatography, and pharmacokinetic parameters were analyzed by using non-compartmental analysis. Hepatic and ileal Oatp1a5, P-gp, and Oct1 mRNA expressions were determined by real-time PCR. ResultsSBP of SHR pre-treated with EGCG and received nadolol was significantly higher than those which were not pre-treated with EGCG but received nadolol. Pre-treatment of EGCG resulted in a marked reduction of plasma nadolol maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) by 53% and 51% compared to its control. The 14-day treatment with oral EGCG led to a significant downregulation of mRNA levels of ileal Oatp1a5, P-gp, and Oct1 genes by 4.03-, 8.01- and 4.03-fold; and hepatic P-gp, and Oct1 genes by 2.61- and 2.66-fold. ConclusionThese data concluded that exposure to EGCG could lead to reduced nadolol bioavailability and therefore, uncontrolled raised blood pressure and higher risks of cardiovascular events. Our data suggest that the reduced nadolol bioavailability is associated with the downregulation of ileal Oatp1a5 and Oct1 mRNA levels that subsequently lead to poor absorption of nadolol to the systemic circulation.