Epigallocatechin-3-gallate Group Research Articles

Comparative Analysis of Epigallocatechin-3-Gallate and TNF-Alpha Inhibitors in Mitigating Cisplatin-Induced Pancreatic Damage Through Oxidative Stress and Apoptosis Pathways.

Oxidative stress and inflammation caused by cisplatin, which is frequently used in the treatment of many cancers, damage healthy tissues as well as cancer cells. In this study, we aimed to investigate the effect of epigallocatechin-3-gallate (EGCG) and infliximab (INF) administration on pancreatic endocrine cells in rats treated with systemic cisplatin (CDDP). The rats were randomly divided into 6 groups: group 1 (control group), group 2 (EGCG group), group 3 (CDDP group), group 4 (EGCG + CDDP group), group 5 (CDDP + INF group), and group 6 (EGCG + CDDP + INF group). The study's findings demonstrated that EGCG and INF effectively reduced the cellular damage induced by CDDP in histopathologic investigations of the pancreas. EGCG and INF, whether used individually or in combination, demonstrated a significant reduction in malondialdehyde (MDA) levels and an increase in glutathione (GSH) levels in the rat pancreas compared to the CDDP group. Immunohistochemically, the enhanced presence of insulin and glucagon positivity in the EGCG and INF groups, along with the absence of TUNEL immunopositivity, indicate that both treatments reduced CDDP-induced apoptosis. Furthermore, the observed lack of immunopositivity in TNF-α and 8-OHdG in the groups treated with EGCG and INF, compared to those treated with CDDP, indicates that these substances can inhibit inflammation. EGCG and INF, whether provided alone or together, can potentially reduce the damage caused to pancreatic islet cells by cisplatin. This effect is achieved through their anti-inflammatory and antioxidant properties during the early stages of the condition.

EGCG’s effects on Mean Arterial Pressure and Heart Rate Variability and Their Correlations with Metabolic and Hormonal Profiles in Obese Subjects

This study aimed to investigate the effects of epigallocatechin gallate (EGCG), a potent polyphenol found in green tea, on mean arterial pressure (MAP) and heart rate variability (HRV) in obese subjects along with their associations with metabolic factors. We hypothesized that EGCG treatment could significantly reduce MAP and sympathetic tone, represented by decreased low-frequency power (LF) and LF-to-high frequency power (HF) ratio. Furthermore, we expected that systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP would be positively correlated with obesity parameters, LF, and LF-to-HF ratio. This study is a double-blind, randomized controlled trial. Thai obese subjects with a body mass index (BMI) ≥ 25 kg/m2 (criteria for an Asian population) were randomly allocated into EGCG and placebo groups and received a capsule of 150 mg of EGCG or starch, respectively, twice a day without any dietary restrictions. Clinical and anthropometric data, as well as spontaneous 5-minute HRV measurements in both time and frequency domains, were assessed at baseline (week 0), week 4, and week 8. Additionally, 8-hour fasting blood samples were collected at weeks 0 and 8 to measure metabolic and hormonal levels. EGCG treatment for 8 weeks significantly reduced MAP compared to week 0 and week 4 (P < 0.05 for all). In the EGCG treatment group, there was a significant increase in the LF-to-HF ratio and a nonsignificant decrease in HF at week 8 compared to week 0. LF showed a trend toward increasing in week 8 of EGCG treatment compared to week 4. For correlation analysis at week 0, SBP had significant positive correlations with BMI, percent fat, fat mass, serum leptin and insulin levels, and the homeostatic model assessment for insulin resistance (HOMA-IR) (R = 0.468-0.593, p<0.05 for all) but had negative correlations with the quantitative insulin sensitivity check index (QUICKI) and HDL-cholesterol (R = (-0.437)-(-0.468), P <0.05 for all). DBP was positively correlated with age and HF in normal units (nu) (R = 0.412-0.568, p<0.05 for all), but was negatively correlated with height, HDL-cholesterol, LF in ms (R = (-0.379)-(-0.509), P <0.05 for all). MAP showed significant positive correlations with age, BMI, percent fat, fat mass, serum leptin levels, and HOMA-IR (R = 0.370-0.459, P < 0.05 for all), but had a negative correlation with HDL-cholesterol (R = -0.522, P = 0.004). EGCG treatment over an 8-week duration reduced MAP, a pivotal component of overall blood pressure in obese individuals, and exhibited a significant increase in the LF/HF ratio, tending toward an increase in LF and a non-significant decrease in HF. We postulate that the decrease in MAP may be attributed to EGCG's direct or indirect vasodilatory effects, potentially through the stimulation of nitric oxide production, reduced oxidative stress, and/or decreased levels of kisspeptin, a vasoconstrictive substance, as reported by previous studies. An increase in the LF/HF ratio could reflect a shift toward sympathetic nervous system dominance (LF) and/or a decrease in parasympathetic nervous system activity (HF) indicating a compensatory response to the reduced blood pressure post-vasodilation. HDL cholesterol showed negative correlations with SBP, DBP, and MAP, reflecting its protective benefit against high blood pressure. In summary, 8 weeks of EGCG treatment resulted in a significant decrease in MAP and an increase in the LF/HF ratio, reflecting EGCG’s primary vasodilatory effects and a compensatory increase in sympathetic nervous system activity. The research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R015932003, R0159333013 and R016132012). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

(-)-Epigallocatechin-3-O-Gallate Regulates Muscle Growth, Antioxidant Status, and Nutritional Composition of Juvenile Common Carp (Cyprinus carpio L.)

Among the polyphenolic compounds commonly found in green tea, (-)-epigallocatechin-3-gallate (EGCG) is known to have various functions, including the promotion of antioxidant and myofiber growth in mammals. However, the effect of EGCG on common carp (Cyprinus carpio L.) remains poorly understood. To evaluate the role of EGCG on juvenile common carp, 255 fish (initial weight 17.33 ± 0.34 g) were fed with five experimental diets containing 0, 0.05, 0.25, 0.5, and 1 g/kg EGCG. The results showed that diet supplementation with 0.05–0.5 g/kg EGCG supplementation significantly enhanced the specific growth rate (SGR) and reduced the feed conversion ratio (FCR). Weight gain rate (WGR) was significantly enhanced in the 0.25 and 0.5 g/kg EGCG groups. As for antioxidants, 0.25–1 g/kg EGCG significantly reduced protein carbonyl (PC) content and upregulated superoxide dismutase (sod) gene expression in the muscle. As for muscle nutritional composition, 0.05–0.5 g/kg EGCG increased total amino acid (TAA) and flavor amino acid (FAA) contents, likely via the rapamycin (mTOR) signaling pathway. Muscle n-3 polyunsaturated fatty acids (n-3 PUFA) content was increased with 0.5 g/kg EGCG, presumably owing to the upregulation of fatty acyl elongase 5 (elovl5), long-chain fatty acyl-CoA synthetase 6 (acsl6), and peroxisome proliferator-actiated receptor α (pparα). Dietary EGCG (0.05–1 g/kg) significantly increased muscle hardness and chewiness, accompanied by an increase in myofiber density. EGCG supplementation (0.25–1 g/kg) increased the pH value and reduced lactate contents in the muscle. However, muscle crude lipid and hydroxyproline contents significantly decreased with 1 g/kg EGCG. Overall, quadratic regression analysis of WGR, SGR, TAA, and FAA showed that optimal EGCG (0.46–0.52 g/kg) dietary supplementation improved the growth and nutritional composition of juvenile common carp.

Exploring the effects of epigallocatechin gallate on lipid metabolism in the rat steatotic liver during normothermic machine perfusion: Insights from lipidomics and RNA sequencing

BackgroundHepatic steatosis is the leading cause of discarded liver grafts. Defatting steatotic liver grafts using drug combinations during ex vivo normothermic machine perfusion (NMP) has been reported. However, the effectiveness of NMP in reducing fat content using epigallocatechin gallate (EGCG) as a single defatting agent and its effect on lipid metabolism are poorly investigated. MethodsIn this study, an NMP system was set up to perfuse a steatotic liver from a rat model with 10 mM EGCG. Livers without EGCG served as NMP controls, whereas static cold-preserved livers in the University of Wisconsin medium were used as static cold storage controls. Liver enzyme, reactive oxygen species (ROS), histology, and lipid content assessments were conducted post-perfusion, complemented by lipidomics, RNA sequencing, and western blotting to determine the lipid metabolism changes. ResultsEGCG during NMP reduced hepatocellular injury markers and defatted steatotic liver grafts. Additionally, we observed a significant increase in triglyceride (TG) content in the perfusate post-NMP in the NMP + EGCG group, suggesting TG output from the liver. Furthermore, lipidomics analysis revealed that EGCG primarily affected metabolites involved in glycerophospholipid (GP) and glycerolipid (GL) metabolism. Further, the RNA sequencing indicated the modulation of these metabolic pathways via ECGC, which was associated with the downregulated Lpin1 and Gpat3 expression. ConclusionsEGCG defats steatotic livers as a single defatting agent during NMP by promoting GL and GP metabolism via decreasing Lpin1 and Agpat9 levels.

Decellularized human amniotic membrane loaded with epigallocatechin-3-gallate accelerated diabetic wound healing

Diabetic wounds, as one of the most important complications of diabetes, face many challenges in treatment. Herein we investigated whether decellularized human amniotic membrane (dAM) loaded with epigallocatechin-3-gallate (EGCG) could promote healing in diabetic rats. Sixty diabetic rats were randomly planned into the untreated group, dAM group, EGCG group, and dAM + EGCG group. On days 7, 14, and 21, five rats from each group were sampled for stereological, molecular, and tensiometrical assessments. Our finding revealed that the wound closure rate, the total volumes of new epidermis and dermis, the numerical densities of fibroblasts, blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were considerably increased in the treated groups than in the untreated group, and these changes were more obvious in the dAM + EGCG ones. Furthermore, the expression of TGF-β, bFGF, and VEGF genes were significantly upregulated in all treated groups compared to the untreated group and were greater in the dAM + EGCG group. This is while expression of TNF-α and IL-1β, as well as cell numerical densities of neutrophils and macrophages decreased more considerably in the dAM + EGCG group in comparison to the other groups. In conclusion, it was found that using both dAM transplantation and EGCG has more effect on diabetic wound healing.

Alleviation effects of epigallocatechin-3-gallate against acute kidney injury following severe burns

BackgroundBurn patients often face a high risk of acute kidney injury (AKI) after severe burn injuries, meanwhile epigallocatechin-3-gallate (EGCG) has been proven to be effective in alleviating organ injury.MethodsThis study used the classical burn model in rats. Thirty model rats were randomly divided into a Burn group, a Burn + placebo group, a Burn + EGCG (50 mg/kg) group, and ten non-model rats as Sham group. The urinary excretion of the rats was subsequently monitored for a period of 48 h. After 48 h of different treatments, rat serum and kidneys were taken for the further verification. The efficacy of EGCG was assessed in pathological sections, biochemical indexes, and at the molecular level.ResultsPathological sections were compared between the Burn group and Burn + placebo group. The rats in the Burn + EGCG group had less kidney damage. Moreover, the EGCG group maintained significantly elevated urine volumes, biochemical indexes manifested that EGCG could reduce serum creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL) level and inhibit the oxidation-related enzyme malondialdehyde (MDA) level, meanwhile the superoxide dismutase (SOD) level was increased. The molecular level showed that EGCG significantly reduced the mRNA expression levels of the inflammation-related molecules interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).ConclusionThe research indicated that EGCG had an alleviating effect on kidney injury in severely burned rats, and its alleviating effects were related to improving kidney functions, alleviating oxidative stress, and inhibiting the expression of inflammatory factors.

Hyperbaric Oxygen in Combination with Epigallocatechin-3-Gallate Synergistically Enhance Recovery from Spinal Cord Injury in Rats.

Spinal cord injury (SCI) following trauma is a devastating neurological event that can lead to loss of sensory and motor functions. However, the most effective measures to prevent the spread of damage are treatment measures in the early stages. Currently, we investigated the combined effects of hyperbaric oxygen (HBO) along with epigallocatechin-3-gallate (EGCG) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley rats were randomly planned into five equal groups (n=18). In addition to sham group that only underwent laminectomy, SCI rats were allocated into 4 groups as follows: control group; HBO group; EGCG group; and HBO+EGCG group. Tissue samples at the lesion site were obtained for stereological, immunohistochemical, biochemical, and molecular evaluation. In addition, behavioral tests were performed to assess of neurological functions. The finding indicated that the stereological parameters, antioxidant factors (CAT, GSH, and SOD), IL-10 gene expression levels and neurological functions were considerably increased in the treatment groups in comparison with control group, and these changes were more obvious in the HBO+EGCG group (P<0.05). On the other hand, we observed that the density of apoptotic cells and gliosis, the biochemical levels of MDA and the expression levels of inflammatory genes (TNF-α and IL-1β) in the treatment groups, especially the HBO+EGCG group, were considerably reduced in comparison with control group (P<0.05). We conclude that co-administration of HBO and EGCG has a synergistic neuroprotective effects in animals undergoing SCI.

Topotekan, karvakrol, epigallokateşin gallat ve kombinasyonlarının nöroblastom ve astrosit hücrelerinde apoptotik süreç üzerine etkisinin değerlendirilmesi

Neuroblastoma is the sympathetic nervous system cancer. It most commonly affects children under 5 years of age and is the most common solid tumor in childhood. Topotecan is a topoisomerase 1 inhibitor. Carvacrol and Epigallocatechin gallate are naturally derived substances with anticancer, antioxidant, and apoptotic properties. The aim of our study was to evaluate the effects of topotecan, carvacrol, EGCG, topotecan+carvacrol, and topotecan+ epigallocatechin gallate combinations on the apoptotic signaling pathway. IC50 values were determined in neuroblastoma and healthy astrocyte cells using the MTT assay. Apoptotic mRNA expressions (topoisomerase 1 and 2, p53, BCL2, BAX, caspase 9, caspase 3, IL1, TNFα) in astrocytes and neuroblastoma cells at the neuroblastoma IC50 dose were analyzed using quantitative real-time PCR. We found that topotecan and carvacrol did not exhibit selective cytotoxic effects between healthy astrocytes and neuroblastoma cells. However, we found that the combination of topotecan+ epigallocatechin gallate and topotecan+carvacrol with epigallocatechin gallate showed selective cytotoxic effects on the neuroblastoma cell line compared to astrocyte cells. The obtained mRNA results can be interpreted as the initiation of apoptosis in neuroblastoma cells in the topotecan, carvacrol, epigallocatechin gallate, and topotecan+epigallocatechin gallate groups. Further studies are needed to investigate this matter in more detail.

Efficacy of anti-sebum moisturizing cream containing 2% l-carnitine and 5% epigallocatechin gallate in seborrhea: A randomized clinical trial.

Seborrhea leads to facial greasiness and unpleasant feeling. People with seborrhea also have trouble with selecting moisturizers. l-Carnitine and epigallocatechin gallate (EGCG) are reported anti-sebum properties. However, neither efficacy comparison nor the combination effect of the two topical anti-sebum agents was studied. Moisturizing cream with these agents is supposed to provide skin with an optimal water-oil balance. To compare the efficacy of moisturizer containing 2% l-carnitine or 5% EGCG alone on sebum controlling, and the synergistic effect of these two agents. Three study creams were formulated by adding three kinds of anti-sebum agents which were 2% l-carnitine, 5% EGCG, and 2% l-carnitine plus 5% EGCG in moisturizing cream base of dimethicone and glycerin. A randomized clinical trial was conducted. Ninety subjects, divided into three groups, applied the cream for 4 weeks. Sebum level, skin capacitance, and transepidermal water loss (TEWL) were evaluated at Weeks 0, 1, 2, and 4. Life qualities and subjective outcomes were assessed before and after treatment. The mean sebum reduction from baseline was statistically significant in all treatment groups (p < 0.01). The median time to oil control was longer in l-carnitine group. The combine group had significantly greater anti-sebum efficacy than l-carnitine group (p = 0.009). All three groups had significant improvement of other objective parameters and subjective outcomes. The anti-sebum moisturizing cream exhibited beneficial effect on the sebum reduction with improve skin hydration in people with seborrhea and made users satisfied. The EGCG group and the combine group show the greater anti-sebum effect than the l-carnitine group.

Biochemical, hematological, peripheral smear and weight evaluation of low dose Epigallocatechin Gallate in Diethylnitrosamine administered rats

Background: Currently, with the development of technology, the use of many chemicals especially Diethylnitrosamine (DEN) in agriculture and industry has increased. The polyphenolic compounds of Epigallocatechin gallate (EGCG) is the active ingredient of green tea. It has been reported that green tea has antioxidant effects. In this study, effects of low dose Epigallocatechin gallate (EGCG), against exposure of Diethylnitrosamine administered rats. &#x0D; Methods: As a group, groups were divided into five groups of ten rats for the application as Control, Sham, DEN EGCG and DEN+EGCG. The parameters analyzed are hemogram, biochemical, peripheral smear and weight. &#x0D; Results: DEN injection has significantly increased LDH, AST, ALT and ALP values, Which are signs of hepatocyte injuries. The number of WBCs increased in the EGCG group. In terms of HDL and TChol levels, the group in which DEN+EGCG were applied together was found to be the highest and TG and LDL levels were found to be lowest. The current study will be a comprehensive study demonstrating the effects of low-dose EGCG against DEN-administred rats.

Release and MMP-9 Inhibition Assessment of Dental Adhesive Modified with EGCG-Encapsulated Halloysite Nanotubes

Degradation of the collagen fibrils at the dentin-resin interface by the enzymatic activity of matrix metalloproteinases (MMPs) has been known to permit some dental restoration complications, such as microleakage, secondary caries, and, ultimately, restoration failures. This study aimed to evaluate a modified adhesive by adding an MMP inhibitor from green tea extract with and without nanotube encapsulation to sustain the drug release. Epigallocatechin-3-gallate (EGCG) and Halloysite nanotubes (HNTs) were prepared to produce three variant combinations of modified adhesive (EGCG, EGCG-encapsulated HNT, and EGCG-free HNT). The drug loading efficiency and EGCG release over time were evaluated using UV-vis spectrometry. MMP-mediated β-casein (BCN) cleavage rate assays were used to determine the ability of the EGCG in eluates of the adhesive to inhibit MMP-9 activities. For up to 8 weeks, HNT encapsulation reduced release to a statistically significant level. MMP-mediated β-casein cleavage rate assays showed a significant decrease for the EGCG groups compared to the non-EGCG adhesive groups. Furthermore, the use of HNT for EGCG encapsulation to modify a dental adhesive helped slow down the rate of EGCG release without impacting its MMP inhibitory capabilities, which may help to maintain the dentin-resin interface's integrity over the long term after dental restoration placement.

Effect of EGCG Extracted from Green Tea against Largemouth Bass Virus Infection.

(1) Background: Largemouth bass virus (LMBV) is a major viral pathogen in largemouth bass (Micropterus salmoides) aquaculture that often causes high mortality and heavy economic losses, thus developing treatments to combat this pathogen is of great commercial importance. Green tea is a well-known medicinal plant that contains active ingredients with antiviral, antibacterial, and other biological activities. The goals of this study were to explore the effect and mechanism of green tea source compounds on LMBV and provide data to serve as the basis for the screening of targeted drugs in the future. In this study, we evaluated the effects of the main component of green tea, epigallocatechin-3-gallate (EGCG), against LMBV infection. (2) Methods: The safe working concentration of EGCG was identified by cell viability detection and light microscopy. The antiviral activity and mechanism of action of EGCG against LMBV infection were evaluated with light microscopy, an aptamer 6-carboxy-fluorescein-based fluorescent molecular probe, and reverse transcription quantitative PCR. (3) Results: The safe working concentration of EGCG was ≤10 μg/mL. EGCG showed significant anti-LMBV infection activity in a concentration-dependent manner, and it also destroyed the structure of virus particles. EGCG impacted the binding of virus particles to cell receptors and virus invasion into the host cells. Inhibitory effects of EGCG on LMBV particles, LMBV binding to the host-cell membrane, and LMBV invasion were 84.89%, 98.99%, and 95.23%, respectively. Meanwhile, the effects of EGCG subsequently were verified in vivo. The fatality rate of the LMBV + EGCG group was significantly lower than that of the LMBV group. (4) Conclusions: Our results suggest that EGCG has effective antiviral properties against LMBV and may be a candidate for the effective treatment and control of LMBV infections in largemouth bass aquaculture.

Effects of green tea polyphenols on inflammation and iron status.

Inflammation is an underlying problem for many disease states and has been implicated in iron deficiency (ID). This study aimed to determine whether iron status is improved by epigallocatechin-3-gallate (EGCG) through reducing inflammation. Thirty-two male Sprague-Dawley rats were fed an iron-deficient diet for 2 weeks and then randomly divided into four groups (n 8 each): positive controls, negative controls, lipopolysaccharide (LPS, 0⋅5 mg/kg body weight), and LPS + EGCG (LPS plus 600 mg EGCG/kg diet) for 3 additional weeks. The study involved testing two control groups, both treated with saline. One group (positive control) was fed a regular diet containing standard iron, while the negative control was fed an iron-deficient diet. Additionally, two treatment groups were tested. The first group was given LPS, while the second group was administered LPS and fed an EGCG diet. Iron status, hepcidin, C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were measured. There were no differences in treatment groups compared with control in CRP, hepcidin, and liver iron concentrations. Serum iron concentrations were significantly lower in the LPS (P = 0⋅02) and the LPS + EGCG (P = 0⋅01) than in the positive control group. Compared to the positive control group, spleen iron concentrations were significantly lower in the negative control (P < 0⋅001) but not with both LPS groups. SAA concentrations were significantly lower in the LPS + EGCG group compared to LPS alone group. EGCG reduced SAA concentrations but did not affect hepcidin or improve serum iron concentration or other iron markers.

The durability of resin-dentine bonds are enhanced by epigallocatechin-3-gallate-encapsulated nanohydroxyapatite/mesoporous silica.

Biomimetic nanohydroxyapatite (nHAp) has long been used as a biocompatible material for bone repair, bone regeneration, and bone reconstruction due to its low toxicity to local or systemic tissues. Various cross-linkers have been employed to maintain the structure of collagen; these include epigallocatechin-3-gallate (EGCG), which can fortify the mechanical properties of collagen and withstand the degradation of collagenase. We hypothesized that EGCG combined with nHAp may promote resin-dentin bonding durability. Here, we examined the effect of epigallocatechin-3-gallate-encapsulated nanohydroxyapatite/mesoporous silica (EGCG@nHAp@MSN) on thermal stability and remineralization capability of dentin collagen. Dentin slices (2 × 2 × 1 mm3 ) were obtained and completely demineralized in a 10% phosphoric acid water solution. The resulting dentin collagen matrix was incubated with deionized water, EGCG, nHAp@MSN, and EGCG@nHAp@MSN. The collagen thermal degradation temperature was assessed utilizing differential scanning calorimetry analysis, which indicated that EGCG, nHAp@MSN, and EGCG@nHAp@MSN reinforced collagen's capability to resist thermal degradation. EGCG@nHAp@MSN resulted in the highest increase in denaturation temperature. Thermogravimetric analysis showed that both nHAp@MSN and EGCG@nHAp@MSN achieved a higher residual mass than the EGCG and control groups. Fourier transform infrared spectroscopy was performed to examine the interaction between EGCG@nHAp@MSN and dentin collagen. The EGCG@nHAp@MSN sample exhibited stronger dentin microhardness and uppermost bond strength after thermocycling. EGCG significantly enhanced collagen's capability to resist thermal degradation. In summary, EGCG and nHAp@MSN may work together to assist the exposed collagen to improve resistance to thermal cycling and promote remineralization while also strengthening the durability of resin-dentin bonds.

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.

Epigallocatechin-3-Gallate Decreases Plasma and Urinary Levels of p-Cresol by Modulating Gut Microbiota in Mice.

p-Cresol (PC), a gut bacterial product of tyrosine catabolism, is recognized as a uremic toxin that has negative biological effects. Lowering the plasma PC level by manipulating the gut bacterial composition represents a promising therapeutic strategy in chronic kidney disease. This study was conducted to reveal whether epigallocatechin-3-gallate (EGCG) decreases plasma PC levels by limiting its bacterial production in a mouse model. The PC concentration in the samples was measured by high-performance liquid chromatography (HPLC) after treatments with sulfatase and β-glucuronidase. The results showed that the addition of EGCG to the diet decreased the plasma and urinary concentrations of PC in a dose-dependent manner, with a statistically significant difference between the control group and the 0.2% EGCG group. However, once EGCG was enzymatically hydrolyzed to epigallocatechin (EGC) and gallic acid, such effects were lost almost completely. The addition of 0.2% EGCG in the diet was accompanied by a decreased abundance of Firmicutes at the phylum level and Clostridiales at the order level, which constitute a large part of PC produced from tyrosine. In conclusion, EGCG, not EGC, reduced plasma and urinary concentrations of PC in mice by suppressing its bacterial production with accompanying alteration of the relative abundance of PC producers.

Enhancing adhesive–dentin interface stability of primary teeth: From ethanol wet-bonding to plant-derived polyphenol application

ObjectivesTo investigate whether the adhesive–dentin interface stability of primary teeth would be enhanced by epigallocatechin-3-gallate (EGCG) with ethanol wet-bonding. MethodsNon-caries primary molars were sliced to achieve a flat dentin surface and etched then randomly distributed into five groups in accordance with different treatments: group 1, no treatment; group 2, applying absolute ethanol wet-bonding for 60 s; groups 3–5, applying 0.1%, 0.5%, and 1% (w/v) EGCG-incorporating ethanol wet-bonding (0.1%, 0.5%, and 1% EGCG) for 60 s. Singlebond universal adhesive was then applied followed by resin composite construction. Microtensile bond strength, fracture mode, and nanoleakage at adhesive–dentin interface were evaluated after 24 h of water storage or 10,000 times of thermocycling. Zymography of hybrid layer, biofilm formation of Streptococcus mutans by CLSM, FESEM, and MTT test, and cytotoxicity by CCK-8 assay were respectively assessed. ResultsIrrespective of thermocycling, the dentin bond strength was preserved with reduced nanoleakage in the 0.5% and 1% EGCG groups. Furthermore, the activity of endogenous proteases and the growth of Streptococcus mutans biofilm were inhibited after treatment with 0.5% and 1% EGCG/ethanol solutions (groups 4 and 5). CCK-8 results of the 0.1% and 0.5% EGCG groups showed acceptable biocompatibility. ConclusionsTreatment by EGCG/ethanol solutions effectively enhanced the bond stability of primary teeth at the adhesive–dentin interface. Clinical significanceSynergistic application of EGCG and ethanol wet-bonding suggesting a promising strategy to improve dentin bonding durability with bacterial biofilm inhibition, thus increasing resin-based restorations’ service life in primary dentition.

Epigallocatechin Gallate Protects Diabetes Mellitus Rats Complicated with Cardiomyopathy through TGF-β1/JNK Signaling Pathway.

Epigallocatechin gallate (EGCG) is the main component of rhubarb tannin, with antioxidant, anti-angiogenic, anti-cancer and antiviral activities. Diabetes mellitus (DM) is a high blood sugar and protein metabolism disorder syndrome, which is caused by absolute or relative factors, such as deficiency of insulin and oxidative stress. Diabetes cardiomyopathy (DCM) is one of the most frequent complications of DM. This study aims to explore whether EGCG can improve diabetic complication, myocardial fibrosis, in diabetic rats with an intraperitoneal injection of streptozotocin (STZ) through the transforming growth factor β1 (TGF-β1)/C-Jun N -terminal kinase (JNK) signaling pathway. 50 male SD rats were randomly divided into five groups, including the control group, model group, and EGCG drug groups (10 mg/kg, 20 mg/kg, 40 mg/kg), with 10 rats in each group. Rats, except for the control group, were intraperitoneally injected with STZ (65 mg/kg) to induce the diabetic rats model. EGCG drug groups were given distilled water according to the dose, while the control group and model group were given the same volume of distilled water for 12 weeks. The levels of glucose (GLU), triglyceride (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in serum were detected by ELISA of all rats. Myocardial function was observed by HE, Masson staining and Sirius red staining in DCM rats. Immunohistochemistry was used to detect the expression of Collagen I (COL-I) and Collagen III (COL-III), and detect the degree of myocardial fibrosis of DM rats. Western blot was used to detect the expression of matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinase (TIMPs), TGF-β1, JNK and p-JNK in the myocardium. Compared to the model group, the levels of GLU, TG, CHO, and LDL in serum were decreased while the level of HDL in serum was increased in EGCG groups rats; cardiac index and left ventricular mass index were decreased while heart function was improved in EGCG groups rats; the expressions of the COL-I and COL-III were decreased in EGCG groups, and the high dose group was the best; the expressions of TGF-β1, JNK, p-JNK, and TIMP-1 were down-regulated, and the expression of MMP-9 was up-regulated in EGCG groups. The results demonstrated that EGCG could improve STZ-induced diabetic complication, i.e., myocardial fibrosis, in diabetic rats, and protect their heart through TGF-β1/JNK signaling pathway.

(-)-Epigallocatechin Gallate Attenuates Spinal Motoneuron Death Induced by Brachial Plexus Root Avulsion in Rats.

Recent studies have indicated that epigallocatechin gallate (EGCG) benefits a variety of neurological insults. This study was performed to investigate the neuroprotective effect of EGCG after brachial plexus root avulsion in SD rats. One hundred twenty SD rats were randomized into the following three groups: an EGCG group, an Avulsion group, and a Sham group. There were 40 rats in each group. EGCG (100 mg/kg, i.p.) or normal saline was administered to rats immediately following the injuries. The treatment was continued from day 1 to day 7, and the animals were sacrificed on days 3, 7, 14, and 28 post-surgery for the harvesting of spinal cord samples for Nissl staining, immunohistochemistry (caspase-3, p-JNK, p-c-Jun), and western blot analysis (p-JNK, JNK, p-c-Jun, c-Jun). EGCG treatment caused significant increases in the percentage of surviving motoneurons on days 14 and 28 (p<0.05) compared to the control animals. On days 3 and 7 after avulsion, the numbers of caspase-3-positive motoneurons in the EGCG-treated animals were significantly fewer than in the control animals (p<0.05). The numbers of p- JNK-positive motoneurons and the ratio of p-JNK/JNK were no significant differences between the Avulsion group and the EGCG-treated group after injury at any time point. The numbers of p-c-Jun-positive motoneurons and the ratio of p-c-Jun/c-Jun were significantly lower in the EGCG-treated group compared with the Avulsion group at 3d and 7d after injury (p<0.05). Our results indicated that motoneurons were protected by EGCG against the cell death induced by brachial plexus root avulsion, and this effect was correlated with inhibiting c-Jun phosphorylation.

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.