Effects Of Epigallocatechin-3-gallate Research Articles

Exploring the Potential of Epigallocatechin Gallate in Combating Insulin Resistance and Diabetes

Background/Objectives: In this study, the potential effects are evaluated of epigallocatechin gallate (EGCG) on the prognosis of diabetes and insulin resistance. Methods: In an experiment, 35 male Wistar albino rats were used and in the streptozotocin (STZ)-induced diabetic rats, the effects were examined of different doses (50 mg/kg, 100 mg/kg, 200 mg/kg) of EGCG on metabolic parameters associated with diabetes and insulin resistance. Results: The findings show favorable effects of EGCG on fasting blood glucose levels, insulin secretion, insulin resistance, and beta cell function. In this study, it was observed that EGCG was able to significantly lower fasting blood glucose levels, especially at high doses (200 mg/kg), providing the most significant improvement. Furthermore, EGCG has been found to reduce insulin resistance and improve insulin sensitivity by increasing insulin secretion. When the biochemical parameters of increased insulin secretion are evaluated, it is also observed that it creates clinically significant changes. At doses of 100 mg/kg and 200 mg/kg, EGCG has the potential to help control diabetes by most effectively improving insulin resistance and beta cell function. The study results suggest that EGCG, especially at high doses, is an effective component in the treatment of diabetes and the management of insulin resistance. Conclusions: The inclusion of EGCG as a natural flavonoid in medical nutrition therapy may contribute to glycemic control and improve insulin sensitivity in individuals with diabetes. These findings suggest that EGCG may be used as an alternative option in the treatment of diabetes and future studies may further clarify the potential benefits in this area.

Effects of epigallocatechin gallate on microbial communities of rainbow trout fillets during ice storage and identification of biogenic amines-producing bacteria

Effects of epigallocatechin gallate on microbial communities of rainbow trout fillets during ice storage and identification of biogenic amines-producing bacteria

(−)-Epigallocatechin-3-gallate (EGCG) ameliorates ovalbumin-induced asthma by inhibiting inflammation via the TNF-α/TNF-R1/NLRP3 signaling pathway

(−)-Epigallocatechin-3-gallate (EGCG) is a polyphenol in green tea with potential lung-protective effects. However, the effects of EGCG on airway inflammation in asthma remain unclear. The aim of this study was to investigate the effect and mechanism of EGCG on asthmatic airway inflammation. In this study, the therapeutic effects of EGCG on ovalbumin (OVA)-induced asthmatic mice were tested first. Second, the effects of EGCG on airway inflammation, airway hyperresponsiveness (AHR), airway mucus hypersecretion, cell apoptosis and differential genes were investigated. Finally, the relationships between the effects of EGCG on airway inflammation and the TNF-α/TNF-R1/NLRP3 signaling pathway in asthmatic mice were explored. The results showed that EGCG could attenuate AHR, alleviate the symptoms of alveolar wall thickening and inflammatory cell infiltration, decrease the levels of inflammatory cytokines and airway mucus markers, reduce apoptosis and reactive oxygen species (ROS) and increase the mitochondrial membrane potential (MMP) in primary lung cells in asthmatic mice. Additionally, EGCG significantly inhibited the activation of the TNF-α/TNF-R1/NLRP3 signaling pathway in the lung tissues of asthmatic mice. The lowest binding free energies of EGCG with TNF-α, TNF-R1 and NLRP3 were −11.6, −11.6 and −8.2 kcal/mol, respectively. Moreover, the equilibrium dissociation constant (KD) of EGCG and TNF-R1was 26.05 μmol/L. EGCG-mediated inhibition of TNF-α/TNF-R1/NLRP3 signaling pathway activation was blocked in LPS-induced BEAS-2B and RAW264.7 cells overexpressing TNF-α. Consequently, EGCG effectively attenuated AHR and inhibited airway inflammation and airway mucus hypersecretion in asthmatic mice, and these effects may be closely related to the TNF-α/TNF-R1/NLRP3 signaling pathway.

Epigallocatechin‐3‐Gallate Ameliorates Diabetic Kidney Disease by Inhibiting the TXNIP/NLRP3/IL‐1β Signaling Pathway

ABSTRACTRecent research indicates that the activation of the NLRP3 inflammasome is crucial in the development of diabetic kidney disease (DKD). Epigallocatechin‐3‐gallate (EGCG), the predominant catechin in green tea, has been noted for its anti‐inflammatory properties in DKD. However, the specific mechanisms are not yet fully understood. In this study, our objective was to explore the effects of EGCG on podocytes and in diabetic kidney disease (DKD) mice and investigate how EGCG modulates the TXNIP/NLRP3/IL‐1β signaling pathway in DKD, both in podocytes and animal models. In vitro, we co‐cultured podocytes with EGCG and detected the viability, apoptosis, inflammation and the TXNIP/NLRP3/IL‐1β signaling pathway. In vivo, DKD mice were given EGCG via oral gavage, followed by evaluations of renal function, inflammation, and the aforementioned signaling pathway. Our findings revealed that oxidative stress, inflammatory cytokines, and the TXNIP/NLRP3/IL‐1β pathway were upregulated in podocytes exposed to high glucose (HG) and in the kidneys of DKD mice. However, EGCG treatment reduced the expression of the NLRP3 inflammasome and its associated proteins, including TXNIP, ASC, caspase‐1, and IL‐1β, as well as the levels of ROS and inflammatory factors such as TNF‐α, IL‐6, and IL‐18. Furthermore, in vivo, EGCG improved kidney function, reduced albuminuria and body weight, and alleviated renal pathological damage. In summary, our study suggests that EGCG mitigates inflammation in podocytes and DKD through the TXNIP/NLRP3/IL‐1β signaling pathway, indicating potential benefits of EGCG or green tea in managing DKD.

Beneficial Effects of Epigallocatechin Gallate in Preventing Skin Photoaging: A Review.

Skin photoaging, primarily caused by ultraviolet (UV) radiation, leads to skin metabolic disorders, which have adverse psychological and physiological effects on individuals. However, traditional medications for repairing skin photoaging cause side effects. Natural bioactive compounds have been shown to prevent and treat skin photoaging with fewer side effects. Epigallocatechin gallate (EGCG), the main substance in tea polyphenols, is a natural bioactive compound with a range of properties. This review summarizes the beneficial effects and mechanisms of EGCG, as well as the application forms of EGCG in repairing photoaged skin. Results indicated that EGCG has repair effects, including improving elasticity, enhancing moisturization, inhibiting damage, and reducing pigmentation of photoaged skin. It has also been demonstrated that EGCG delivery systems, modified EGCG, and combinations with other bioactive substances could be used for repairing photoaged skin due to its poor stability and low bioavailability. EGCG effectively repairs various types of skin damage caused by UV radiation while maintaining normal skin structure and function. It is, therefore, an effective candidate for repairing photoaged skin. These results could provide references for the development and application of EGCG products for the treatment of photoaged skin.

The Role of Epigallocatechin-3-gallate (EGCG) In Inhibiting MMP3 Expression and Human Pterygium Fibroblast Migration: A Review

Background: Pterygium is characterized by the overgrowth of fibroblasts and the remodeling of the extracellular matrix (ECM), driven by MMPs. The review outlines the pathophysiology of pterygium, emphasizing the role of MMP-3 in cell motility, proteolysis, and angiogenesis. The recurrence rate of pterygium following surgical excision remains a significant challenge, with current adjuvant therapies like mitomycin-C presenting serious side effects. Methods: The review synthesizes findings from various studies on the effects of EGCG on MMP-3 expression and fibroblast migration. It discusses the mechanisms by which EGCG inhibits MMP-3 activity and its potential impact on pterygium progression. Findings: EGCG has been shown to inhibit MMP-3 expression and activity in several models, including mouse Lewis lung carcinoma-derived cells and photoaged hairless mouse models. It also suppresses the migration of human pterygium fibroblast cells, potentially preventing pterygium formation. EGCG's ability to reduce oxidative stress and modulate inflammatory pathways further supports its therapeutic potential. Conclusion: EGCG emerges as a promising agent for inhibiting MMP-3 expression and human pterygium fibroblast migration, offering a safer alternative to current adjuvant therapies. Its anti-inflammatory, antioxidant, and anti-angiogenic properties make it a potential therapeutic option for managing pterygium, warranting further clinical investigation.

Phenotype variability in diet-induced obesity and response to (−)-epigallocatechin gallate supplementation in a Diversity Outbred mouse cohort: a model for exploring gene x diet interactions for dietary bioactives

The flavan-3-ol (−)-epigallocatechin gallate (EGCG) blunts obesity in inbred mice, but human clinical trials have yielded mixed results. Genetic homogeneity in preclinical models may explain translational disconnect between rodents and humans. The Diversity Outbred (DO) mouse model provides genotype and phenotype variability for characterization of gene x environment (i.e., diet) interactions. We conducted a longitudinal phenotyping study in N=50 DO mice. Mice were fed a high-fat diet for 8 weeks and then a high-fat diet + 0.3% EGCG for 8 weeks. We hypothesized that obesity and any protective effects of EGCG would exhibit extreme variability in these genetically heterogeneous mice. As anticipated, DO mice exhibited extreme variation in body composition at baseline (4.0-13.9% fat), after 8 weeks of high-fat diet (6.5-38.1% fat), and after 8 weeks of high-fat diet + EGCG (7.6-42.6% fat), greater than what is observed in inbred mice. All 50 mice gained body fat on the high-fat diet (changes from baseline of +5-+640%). Intriguingly, adiposity variability increased when EGCG was added to the diet (changes from the high-fat diet alone of −52-+390%), with 11/50 mice losing body fat. We postulate that the explanation for this variability is genetic heterogeneity. Our data confirm the promise for EGCG to manage obesity but suggest that genetic factors may exert significant control over the efficacy of EGCG. Larger studies in DO mice are needed for quantitative trait loci mapping to identify genetic loci governing EGCG x obesity interactions and translate these findings to precision nutrition in humans.

Biophysical Analysis of EGCG’s Protective Effects on Camptothecin-Induced Oxidative Stress in Bone-like Cancer Cells Using Electric Cell-Substrate Impedance Sensing (ECIS)

Various medical treatments aim to counteract the impact of oxidants on mammalian cells. One such antioxidant is Epigallocatechin-3-gallate (EGCG), an active ingredient in green tea, which has demonstrated protective effects against cellular oxidants like camptothecin (CAMPT). This study examines how EGCG mitigates CAMPT’s effects on UMR cells, focusing on cell proliferation and biophysical parameters. UMR cells were treated with different CAMPT concentrations and incubated for 72 h. Subsequently, cell proliferation and viability were assessed. In a separate experiment, UMR cells were co-treated with CAMPT and varying EGCG concentrations to evaluate EGCG’s ability to mitigate CAMPT’s oxidative effect. Electric Cell–Substrate Impedance Sensing (ECIS) technology was also used to assess the biophysical parameters of CAMPT-treated UMR cells, including cell monolayer resistance, cell spreading, and cell attachment. The results showed a concentration-dependent decrease in cell proliferation for CAMPT-treated UMR cells. However, co-treatment with EGCG reversed CAMPT’s oxidative effects in a concentration-dependent manner. ECIS technology revealed a decrease in biophysical parameters when UMR cells were treated with CAMPT alone. Statistical analysis indicated significant differences with p-values < 0.05. This study suggests that EGCG effectively protects UMR cells from oxidative stress and highlights its potential role in mitigating oxidative stress in mammalian cells. Additionally, the use of ECIS technology validates its application in corroborating the biological effects of CAMPT and EGCG on UMR cells.

Bioinformatics Analysis and Experimental Validation of Epigallocatechin-3-gallate Against Iopromide-induced Injury in HEK-293 Cells via Anti-oxidative and Anti-inflammation Pathways.

The administration of contrast agents can adversely affect kidney function. Nevertheless, the nephrotoxicity of iopromide in human renal cells, potential therapeutic agents, and the underlying molecular mechanisms have not been thoroughly investigated. The proliferation of HEK-293 kidney cells was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay. Apoptotic cell death was examined using the TUNEL assay and caspase-3 activity measurements. The impacts and potential pathways of epigallocatechin-3-gallate (EGCG) on iopromide-induced renal damage were analyzed through whole transcriptome sequencing. The redox state was assessed by measuring reactive oxygen species (ROS) production and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Iopromide-induced inhibition of cell proliferation and apoptosis in HEK-293 cells was counteracted by EGCG co-treatment. Pathway analysis revealed that molecules related to antioxidant and anti-inflammatory responses, such as ERK1/2, STAT1, and NF-[Formula: see text]B, were pivotal in the action of EGCG. Iopromide-induced ROS production, decreased DPPH scavenging ability, DNA strand breaks, elevated caspase-3 activity, and reduced cell proliferation were all reversed by EGCG co-treatment in HEK-293 cells. The mechanisms likely involve the attenuation of oxidative stress, inflammatory responses, and apoptosis, with regulation through the ERK1/2, STAT1, and NF-[Formula: see text]B pathways. Further research is necessary to confirm the protective effects of EGCG on renal function, particularly against damage induced by contrast agents like iopromide.

EGCG enhances antitumor effect of apatinib in nonsmall cell lung cancer by targeting VEGF signaling to inhibit glycolysis.

Nonsmall cell lung cancer (NSCLC), one of the most aggressive malignancies globally, is characterized by poor prognosis and limited life expectancy. Epigallocatechin-3-gallate (EGCG), a natural polyphenol found in green tea, has emerged as a promising anticancer agent due to its potent antitumor properties. However, the role and the underlying mechanisms of EGCG in NSCLC remain poorly understood. Hence, this research aimed to explore the effect of EGCG on the antitumor effect of apatinib in NSCLC throughvascular endothelial growth factor(VEGF)-regulated glycolysis. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine staining, wound healing, transwell, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and flow cytometry assays were carried out to evaluate the proliferation, migration, invasion, and apoptosis of H1299 cells, respectively. Furthermore, western blot analysis was used to detect the expressions of VEGF, p-vascular endothelial growth factor receptor-2, hypoxia-inducible factor 1α, neuropilin-1, phosphorylated-phosphatidylinositol 3-kinase, and phosphorylated-AKT. The transfection efficiency of H1299 cells with VEGF overexpression plasmid was also assessed by western blot analysis. Glycolysis was analyzed by estimating extracellular acidification rate, lactate concentration, glucose uptake, and the expressions of lactate dehydrogenase A, pyruvate kinase M2, and hexokinase 2. The results demonstrated that VEGF activated glycolysis in NSCLC cells. EGCG alone and apatinib alone or in combination inhibited cell viability, proliferation, invasion, migration, and glycolysis whereas promoted apoptosis in NSCLC cells. EGCG regulated glycolysis levels in NSCLC through VEGF overexpression, and enhanced the antitumor effect of apatinib in NSCLC through VEGF-regulated glycolysis. Taken together, EGCG strengthened the protective effects of apatinib in NSCLC through glycolysis mediated by VEGF.

Molecular interaction mechanisms on (−)-epigallocatechin-3-gallate improving activities of inhibited acetylcholinesterase by selected organophosphorus pesticides in vitro & vivo

(−)-Epigallocatechin-3-gallate (EGCG) is reported to have benefits for the treatment of Alzheimer’s disease by binding with acetylcholinesterase (AChE) to enhance the cholinergic neurotransmission. Organophosphorus pesticides (OPs) inhibited AChE and damaged the nervous system. This study investigated the combined effects of EGCG and OPs on AChE activities in vitro & vivo. The results indicated that EGCG significantly reversed the inhibition of AChE caused by OPs. In vitro, EGCG reactived AChE in three group tubes incubated for 110 min, and in vivo, it increased the relative activities of AChE from less than 20% to over 70% in brain and vertebral of zebrafish during the exposure of 34 h. The study also proposed the molecular interaction mechanisms through the reactive kinetics and computational analyses of density functional theory, molecular docking, and dynamic modeling. These analyses suggested that EGCG occupied the key residues, preventing OPs from binding to the catalytic center of AChE, and interfering with the initial affinity of OPs to the central active site. Hydrogen bonding, conjugation, and steric interactions were identified as playing important roles in the molecular interactions. The work suggests that EGCG antagonized the inhibitions of OPs on AChE activities and potentially offered the neuroprotection against the induced damage.

EGCG inhibits migration, invasion and epithelial-mesenchymal transition of renal cell carcinoma by activating TFEB-mediated autophagy

BackgroundThe incidence of renal cell carcinoma (RCC) is already in the top ten of all types of cancers, with more than 4 %. Epigallocatechin gallate (EGCG), a polyphenolic compound extracted from green tea, has been shown to be effective in the treatment of various tumors. However, limited studies have demonstrated the effect of EGCG on RCC and its underlying molecular mechanisms. MethodsAfter exposure to gradient concentration (0,5,10,20,40,60,80,100 μM) of EGCG, the cell viability of RCC cells was determined by MTT assay. The migration and invasion abilities of RCC cells were investigated by wound healing and transwell assays. The expression levels of proteins involved in the epithelial-mesenchymal transition (EMT) and autophagy were explored by Western blotting assays. The formation of autophagosome was detected by electron microscope and LC3 puncta assays. Nude mouse xenograft model was used as the model system in vivo. ResultsIn the present study, EGCG significantly inhibited the migration, invasion and EMT of RCC cells in a concentrated manner. Further exploration of its mechanism indicated that autophagy is involved in EGCG-mediated metastasis inhibition and EMT inhibition of RCC cells. In addition, EGCG could significantly up-regulate the transcription factor EB (TFEB) and promotes its nuclear localization. The incorporation of TFEB into the nucleus enhanced the transcriptional levels of molecules associated with autophagy. TFEB knockdown inhibited EGCG-mediated autophagy activation, metastasis and EMT inhibition in RCC cells. ConclusionsIn conclusion, these findings demonstrate for the first time that EGCG inhibits migration, invasion, and EMT of RCC by activating TFEB-mediated autophagy. Therefore, the combination of EGCG and TFFB activators or EMT inhibitors is expected to be a promising therapeutic strategy for RCC.

Epigallocatechin gallate enhances sympathetic heart rate variability and decreases blood pressure in obese subjects: a randomized control trial

This study aimed to investigate effects of epigallocatechin gallate (EGCG) on blood pressure (BP) and autonomic nervous system, indicated by 5-min heart rate variability (HRV) measurement in obese subjects, and determine correlations of BP with metabolic factors. In a double-blind, randomized controlled trial, obese subjects (n = 30) were randomly allocated to receive 150 mg EGCG (n = 15) or placebo (n = 15) twice a day without dietary restrictions. After 8-week EGCG treatment, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) significantly decreased, while the low-frequency (LF) to high-frequency power (HF) ratio (LF/HF ratio) significantly increased (P < 0.05 all), indicating a shift toward sympathetic dominance, either directly or indirectly after BP lowering. SBP had positive correlations with obesity parameters, leptin, insulin, and insulin resistance but had a negative correlation with insulin sensitivity. DBP was positively correlated with age and HF in normalized unit, but negatively correlated with height and LF in ms2. High-density lipoprotein cholesterol (HDL-C) was negatively correlated with SBP, DBP, and MAP reflecting its protective effect against elevated BP. In conclusion, the 8-week EGCG treatment decreased BP and increased the LF/HF ratio, reflecting increased sympathetic activity, either a direct EGCG effect or an indirect compensatory response following BP reduction.

The effect of epigallocatechin gallate on Streptococcus Gordonii biofilm formation

Background: Dental caries, as a primary disease in dentistry, is strongly influenced by the presence of biofilms. One of the Gram-positive bacteria that acts as an initiator in the biofilm formation process is Streptococcus gordonii. As the primary catechin in green tea, epigallocatechin gallate (EGCG) is easily found in our daily lives, and it has a broad spectrum of antimicrobial effects. Several studies have revealed that EGCG inhibited the growth of Gram-positive bacteria, including inhibiting biofilm formation by damaging the bacterial cell wall and reducing glucosyltransferase activity. However, there is still limited information that explains the effect of EGCG on S. gordonii bacterial biofilms. Purpose: This study aims to analyze the effect of EGCG in inhibiting the formation of S. gordonii bacterial biofilms. Methods: This study was an in-vitro experimental laboratory study, with samples divided into five groups, namely, the group containing BHIB-bacteria, the BHIB-bacteria-5% sucrose groups, and the treatment groups containing BHIB-bacteria-5% sucrose-EGCG with concentrations of 12.5%, 6.25%, and 3.125%, respectively, incubated for 24 hours. The data was analyzed using the Kruskal–Wallis test. Results: There was a significant difference in the formation of biofilms in S. gordonii bacteria with the addition of 5% sucrose in BHIB compared with the group of S. gordonii bacteria in BHIB. The highest biofilm formation in the group containing bacteria-BHIB-5% sucrose, while the lowest biofilm formation occurred in the treatment group containing bacteria-BHIB-5% sucrose-12.5% EGCG with significant difference between the group. Conclusion: The addition of EGCG 12.5% inhibits the formation of S. gordonii biofilms.

Green Tea Catechin Epigallocatechin Gallate Inhibits Vegetative Cell Outgrowth and Expression of Beta-Lactamase Genes in Penicillin-Resistant Bacillus anthracis Strain PCr.

The green tea catechin epigallocatechin gallate (EGCg) has antimicrobial effects on many bacteria. In this study, we investigated the inhibitory effects of EGCg on Bacillus anthracis spores and vegetative cells. The B. anthracis spores were insensitive to EGCg, but the growth of vegetative cells derived from germinated spores was inhibited by EGCg. Moreover, EGCg decreased the minimum inhibitory concentration of penicillin and meropenem for penicillin-resistant B. anthracis. In the penicillin-resistant B. anthracis strain, the transcription levels of the beta-lactamase genes (bla1 and bla2) decreased significantly following the treatment with 50 µg/mL EGCg. These results suggest that the appropriate application of EGCg may effectively control the penicillin-resistant B. anthracis growth and beta-lactamase production.

Epigallocatechin gallate induces apoptosis in multiple myeloma cells through endoplasmic reticulum stress induction and cytoskeletal disruption

Multiple myeloma (MM) is an incurable plasma cell malignancy that has prompted investigations into new potential therapeutic avenues. Epigallocatechin-3-gallate (EGCG), a major component of green tea, confers antioxidant, anti-inflammatory, and anti-tumor properties. Previous studies have shown that EGCG inhibits proliferation and induces apoptosis of multiple myeloma cells, however its underlying molecular mechanisms are largely unknown. In this study, we accordingly sought to examine the therapeutic effects and underlying mechanisms of EGCG on MM.Initially, using CCK8 (Cell Counting Kit-8) assays and Annexin V-FITC/PI staining, we demonstrated that EGCG dose-dependently reduced cell viability and induced apoptosis in the MM cell lines MM.1S and RPMI 8226. Subsequently, mRNA sequencing of EGCG-treated MM.1S cells revealed a significant upregulation of genes associated with endoplasmic reticulum stress (ERS), including P-eIF2α (phosphorylation-eukaryotic translation initiation factor 2 alpha), ATF4 (activating transcription factor 4), CHOP (C/EBP homologous protein, DDIT3), and PUMA (p53 upregulated modulator of apoptosis, BBC3), which were confirmed at the protein level by western blotting. Furthermore, treatment with the eIF2α inhibitor ISRIB reduced the rates of EGCG-induced apoptosis and promoted increases in the protein expression of all four ER stress-related molecules in MM cells. Additionally, mRNA-seq data revealed a downregulation of α-Tubulin 1b (TUBA1B) expression in EGCG-treated MM cells, which was confirmed by western blotting and immunofluorescence analyses. Moreover, we utilized a mouse model to show that EGCG inhibited myeloma tumor growth, which was inhibited by ISRIB.In summary, the findings of this novel study indicated that EGCG promotes apoptosis of MM cells, both via activation of the ER stress pathway and disruption of cytoskeletal integrity. These findings highlight the multi-faceted anti-tumor effects of EGCG and its potential clinical application in MM treatment.

In Vitro Effect of Epigallocatechin Gallate on Heme Synthesis Pathway and Protoporphyrin IX Production.

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG's role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (<50 µM) did not have an antiproliferative effect over A-431 cells; however, EGCG inhibited clonogenic cell capability. Furthermore, EGCG (<50 µM) improved MAL-PDT cytotoxicity, increasing PpIX and ROS levels, exerting a positive influence on PpIX synthesis, decreasing intracellular iron concentration and modifying HGS enzyme gene expression such as PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells.

Fractionation of debranched starch with different degree of polymerization and its effect of epigallocatechin gallate

Herein, five distinct degrees of polymerization (DP n‾) of debranched starch (DBS) were separated from native corn starch based on their differential solubility in aqueous/ethanol solutions of different volumetric ratios (1:1.5 and 1:3). Compared with the DBSP (DP n‾ 24.53 and DP n‾ 19.36), DBSs (DP n‾ 8.85 and DP n‾ 7.32) were found to have an amorphous crystal structure, resulting in lower thermal stability and an inability to form a complex with iodine. Furthermore, the proportion of rapidly digestible starch (RDS) in DBSP decreased, while the proportions of slow-digestible starch (SDS) and resistant starch (RS) increased. Additionally, the starch microparticles (SMPs) self-assembled from DBSp exhibit a larger particle size and a more regular shape than those formed by DBSs. Moreover, DBS-based SMPs (DBS-SMPs) with the maximum encapsulation efficiency and loading capacity of epigallocatechin gallate (EGCG) in DBSP3.0 (20) reached 88.67% and 22.35%, respectively. The EGCG loaded in EGCG@DBS-SMPs exhibited excellent radical scavenging activity.

Up-regulation of BMAL1 by epigallocatechin-3-gallate improves neurological damage in SBI rats

Brain Muscle ARNT-Like Protein 1 (BMAL1) suppresses oxidative stress in brain injury during surgery. Epigallocatechin-3-gallate (EGCG), a monomer in green tea, has been identified as an antioxidant and a potential agonist for BMAL1. In this work, the mechanism by which BMAL1 is regulated was investigated, as well as the therapeutic effect of EGCG on surgically injured rats. The pathological environment after brain injury during surgery was simulated by excising the right frontal lobe of rats. Rats received an intraperitoneal injection of EGCG immediately after surgery. Neurological scores and cerebral edema were recorded after surgery. Fluoro-Jade C staining, TUNEL staining, western blot, and lipid peroxidation analyses were conducted 3 days later. Here we show that the endogenous BMAL1 level decreased after brain injury. Postoperative administration of EGCG up-regulated the content of BMAL1 around the cerebral cortex, reduced the oxidative stress level, reduced neuronal apoptosis and the number of degenerated neurons, alleviated cerebral edema, and improved neurological scores in rats. This suggests that BMAL1 is an effective target for treating surgical brain injury, as well as that EGCG may be a promising agent for alleviating postoperative brain injury.

(-)-Epigallocatechin 3-gallate protects pancreatic β-cell against excessive autophagy-induced injury through promoting FTO degradation

ABSTRACT Excessive macroautophagy/autophagy leads to pancreatic β-cell failure that contributes to the development of diabetes. Our previous study proved that the occurrence of deleterious hyperactive autophagy attributes to glucolipotoxicity-induced NR3C1 activation. Here, we explored the potential protective effects of (-)-epigallocatechin 3-gallate (EGCG) on β-cell-specific NR3C1 overexpression mice in vivo and NR3C1-enhanced β cells in vitro. We showed that EGCG protects pancreatic β cells against NR3C1 enhancement-induced failure through inhibiting excessive autophagy. RNA demethylase FTO (FTO alpha-ketoglutarate dependent dioxygenase) caused diminished m6A modifications on mRNAs of three pro-oxidant genes (Tlr4, Rela, Src) and, hence, oxidative stress occurs; by contrast, EGCG promotes FTO degradation by the ubiquitin-proteasome system in NR3C1-enhanced β cells, which alleviates oxidative stress, and thereby prevents excessive autophagy. Moreover, FTO overexpression abolishes the beneficial effects of EGCG on β cells against NR3C1 enhancement-induced damage. Collectively, our results demonstrate that EGCG protects pancreatic β cells against NR3C1 enhancement-induced excessive autophagy through suppressing FTO-stimulated oxidative stress, which provides novel insights into the mechanisms for the anti-diabetic effect of EGCG. Abbreviation 3-MA: 3-methyladenine; AAV: adeno-associated virus; Ad: adenovirus; ALD: aldosterone; AUC: area under curve; βNR3C1 mice: pancreatic β-cell-specific NR3C1 overexpression mice; Ctrl: control; CHX: cycloheximide; DEX: dexamethasone; DHE: dihydroethidium; EGCG: (-)-epigallocatechin 3-gallate; FTO: FTO alpha-ketoglutarate dependent dioxygenase; GSIS: glucose-stimulated insulin secretion; HFD: high-fat diet; HG: high glucose; i.p.: intraperitoneal; IOD: immunofluorescence optical density; KSIS: potassium-stimulated insulin secretion; m6A: N6-methyladenosine; MeRIP-seq: methylated RNA immunoprecipitation sequencing; NO: nitric oxide; NR3C1/GR: nuclear receptor subfamily 3, group C, member 1; NR3C1-Enhc.: NR3C1-enhancement; NAC: N-acetylcysteine; NC: negative control; PBS: phosphate-buffered saline; PI: propidium iodide; OCR: oxygen consumption rate; Palm.: palmitate; RELA: v-rel reticuloendotheliosis viral oncogene homolog A (avian); RNA-seq: RNA sequencing; O2 .-: superoxide anion; SRC: Rous sarcoma oncogene; ROS: reactive oxygen species; T2D: type 2 diabetes; TEM: transmission electron microscopy; TLR4: toll-like receptor 4; TUNEL: terminal dUTP nick-end labeling; UTR: untranslated region; WT: wild-type.