Effect Of EGCG Research Articles

Computational Insights Into the Mechanism of EGCG's Binding and Inhibition of the TDP-43 Aggregation.

Misfolding and aggregation of TAR DNA-binding protein, TDP-43, is linked to devastating proteinopathies such as ALS. Therefore, targeting TDP-43's aggregation is significant for therapeutics. Recently, green tea polyphenol, EGCG, was observed to promote non-toxic TDP-43 oligomer formation disallowing TDP-43 aggregation. Here, we investigated if the anti-aggregation effect of EGCG is mediated via EGCG's binding to TDP-43. In silico molecular docking and molecular dynamics (MD) simulation suggest a strong binding of EGCG with TDP-43's aggregation-prone C-terminal domain (CTD). Three replicas, each having 800 ns MD simulation of the EGCG-TDP-43-CTD complex, yielded a high negative binding free energy (ΔG) inferring a stable complex formation. Simulation snapshots show that EGCG forms close and long-lasting contacts with TDP-43's Phe-313 and Ala-341 residues, which were previously identified for monomer recruitment in CTD's aggregation. Notably, stable physical interactions between TDP-43 and EGCG were also detected invitro using TTC staining and isothermal titration calorimetry which revealed a high-affinity binding site of EGCG on TDP-43 (Kd, 7.8 μM; ΔG, -6.9 kcal/mol). Additionally, TDP-43 co-incubated with EGCG was non-cytotoxic when added to HEK293 cells. In summary, EGCG's binding to TDP-43 and blocking of residues important for aggregation can be a possible mechanism of its anti-aggregation effects on TDP-43.

Antimicrobial effects of epigallocatechin-3-gallate, a catechin abundant in green tea, on periodontal disease-associated bacteria

ObjectiveEpigallocatechin-3-gallate (EGCG), a catechin abundant in green tea, exhibits antibacterial activity. In this study, the antimicrobial effects of EGCG on periodontal disease-associated bacteria (Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum, and Fusobacterium periodontium) were evaluated and compared with its effects on Streptococcus mutans, a caries-associated bacterium. ResultsTreatment with 2 mg/ml EGCG for 4 h killed all periodontal disease-associated bacteria, whereas it only reduced the viable count of S. mutans by about 40 %. Regarding growth, the periodontal disease-associated bacteria were more susceptible to EGCG than S. mutans, based on the growth inhibition ring test. As for metabolism, the 50 % inhibitory concentration (IC50) of EGCG for bacterial metabolic activity was lower for periodontal disease-associated bacteria (0.32–0.65 mg/ml) than for S. mutans (1.14 mg/ml). Furthermore, these IC50 values were negatively correlated with the growth inhibition ring (r = −0.73 to −0.86). EGCG induced bacterial aggregation at the following concentrations: P. gingivalis (>0.125 mg/ml), F. periodonticum (>0.5 mg/ml), F. nucleatum (>1 mg/ml), and P. nigrescens (>2 mg/ml). S. mutans aggregated at an EGCG concentration of > 1 mg/ml. ConclusionEGCG may help to prevent periodontal disease by killing bacteria, inhibiting bacterial growth by suppressing bacterial metabolic activity, and removing bacteria through aggregation.

Resveratrol and (-)-Epigallocatechin-3-gallate Regulate Lipid Metabolism by Activating the AMPK Pathway in Hepatocytes.

The purpose of this study was to explore the effects of Res and EGCG on cell growth, cellular antioxidant levels, and cellular lipid metabolism in hepatocytes. In this experiment, leghorn male hepatoma (LMH) cells were used as hepatocytes. The results showed that 6.25-25 μM Res and EGCG had no adverse effects on cell viability and growth. Meanwhile, with the increasing dosage of Res and EGCG, the contents of total cholesterol (TC), total glyceride (TG), and malondialdehyde (MDA) in hepatocytes decreased significantly (p < 0.05), while the contents of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT) increased significantly (p < 0.05). In addition, western blot results showed that Res and EGCG could significantly increase the expression of p-AMPK protein and reduce the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) protein in hepatocytes (p < 0.05). Moreover, q-PCR results showed that with the increase in Res and EGCG, the expression of cholesterol- and fatty acid synthesis-related genes decreased significantly (p < 0.05). In conclusion, Res and EGCG can increase the antioxidant capacity of hepatocytes and reduce the synthesis of TC and TG in hepatocytes by activating AMPK, thereby regulating lipid metabolism in hepatocytes.

Regulation of gene expression by modulating microRNAs through Epigallocatechin-3-gallate in cancer.

Cancer is an intricate ailment that has a higher death rate globally and is characterized by aberrant cell proliferation and metastasis in nature. Since the beginning of healthcare, natural products, especially those derived from plants, have been utilized to support human health. Green tea contains an essential catechin called epigallocatechin gallate, which has anti-proliferative, anti-mutagenic, anti-inflammatory, and antioxidative properties. The anticancer properties of EGCG have been extensively studied using pre-clinical cell culture and animal model systems. Dysregulated miRNA may be a biomarker since it influences the different characteristics of cancer like upholding proliferative signaling, cell death, invasiveness, metastasis, and angiogenesis. EGCG either elevates or lowers the expression of dysregulated miRNAs in cancer. Nonetheless, due to its anticancer properties, greater attention has been paid towards the development of efficient strategies for utilizing EGCG in cancer chemotherapy. This review summarizes the modifying effect of EGCG on miRNAs in cancer after briefly discussing the anticancer mechanisms of EGCG and the function of miRNAs in cancer.

EGCG-induced selective death of cancer cells through autophagy-dependent regulation of the p62-mediated antioxidant survival pathway

The effects of EGCG on the selective death of cancer cells by modulating antioxidant pathways through autophagy were explored in various normal and cancer cells. EGCG positively regulated the p62-KEAP1-NRF2-HO-1 pathway in normal cells, while negatively regulating it in cancer cells, leading to selective apoptotic death of cancer cells. In EGCG-treated MRC5 cells (EGCG-MRC5), autophagic flux was blocked, which was accompanied by the formation of p62-positive aggregates. However, EGCG-treated HeLa cells (EGCG-HeLa) showed incomplete autophagic flux and no aggregate formation. The levels of P-ULK1 S556 and S758 increased in EGCG-MRC5 through AMPK-mTOR cooperative interaction. In contrast, EGCG treatment in HeLa cells led to AMPK-induced mTOR inactivation, resulting in abrogation of P-ULK1 S556 and S758 levels. AMPK knockout in EGCG-HeLa restored positive regulation of the p62-mediated pathway, which was accompanied by increased P-mTOR S2448 and P-ULK1 S758 levels. Knockdown of 67LR in EGCG-HeLa abolished AMPK activity but did not restore the p62-mediated pathway. Surprisingly, both AMPK knockout and 67LR knockdown in EGCG-HeLa markedly increased cell viability, despite differential regulation of the antioxidant enzyme HO-1. In conclusion, EGCG induces the selective death of cancer cells through the modulation of at least two autophagy-dependent and independent regulatory pathways: negative regulation involves the mTOR-ULK1 (S556 and S758)-p62-KEAP1-NRF2-HO-1 axis via AMPK activation, whereas positive regulation occurs through the 67LR-AMPK axis.

EGCG attenuated acute myocardial infarction by inhibiting ferroptosis via miR-450b-5p/ACSL4 axis

BackgroundEpigallocatechin gallate (EGCG) has multiple biological effects such as anti-tumor multiple drug resistance, antioxidation and anti-inflammatory properties. Ferroptosis is the main driving factor of ischemic heart injury, thus inhibiting ferroptosis may prove to be an effective treatment strategy for cardiovascular diseases. However, the role of EGCG on ferroptosis in ischemic myocardium and underlying mechanisms remain uncertain. PurposeThis study was aimed to investigate the effects and potential mechanisms of EGCG on myocardial ischemic-induced ferroptosis both in vitro and in vivo. MethodsCardiomyocyte hypoxia model and mouse acute myocardial infarction (AMI) model were established in vitro and in vivo. MiR-450b-5p and ACSL4 silencing or overexpression plasmids were transfected, with or without EGCG pretreatment. Cell viability was determined by the CCK-8 assay. Hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the morphologic alterations. TTC staining was used to observe the infarction area, and echocardiography was adopted to appraise the heart function. Using flow cytometry, the presence of reactive oxygen species (ROS) was assessed. The content of cardiac troponin I (cTn I), glutathione (GSH), malondialdehyde (MDA), divalent iron ions (Fe2+) and superoxide dismutase (SOD) were detected using reagent kits. A luciferase activity assay was performed to assess the binding ability of miR-450b-5p to ACSL4. Expressions of related genes and proteins were measured by RT-qPCR and western blotting respectively. ResultsEGCG attenuated AMI-induced ferroptosis and improved myocardial ischemia injury, which was associated with reducing iron deposition and cTn I, inhibition of lipid peroxidation, decreasing TFR1 and ACSL4, and upregulating SLC7A11, FTH1 and GPX4. Meanwhile, EGCG pretreatment increased miR-450b-5p expression in ischemic myocardium. Further researches discovered that knockdown of miR-450b-5p partially compromised EGCG-generated protective effect in hypoxia HL-1 cells, while combination with miR-450b-5p mimic could strengthen the potency of EGCG on ischemic myocardium. The dual-luciferase test demonstrated that miR-450b-5p has binding to ACSL4. Furthermore, silencing of ACSL4 synergistically increased the cardioprotective effect of EGCG. More significantly, EGCG treatment regulated the ferroptosis-related proteins expression via miR-450b-5p/ACSL4 axis. ConclusionIn summary, the present study evidently demonstrated that EGCG attenuates myocardial ischemia injury by targeting ferroptosis. Our work revealed the role of miR-450b-5p/ACSL4 axis in AMI for the first time. Further, it also elucidated the molecular mechanisms of EGCG on inhibiting ferroptosis greatly depend on the miR-450b-5p/ACSL4 axis, suggesting that EGCG may act as a novel anti-ferroptosis agent and exert a therapeutic role in AMI.

Co-incorporation of probiotics into 3D printed custard cream with hydrophilic and hydrophobic bioactives

There is an emerging need for food with specific functionality and nutrition. This work investigated the feasibility of developing 3D printed custard cream co-enriched with probiotics, hydrophilic and hydrophobic bioactives. The effect of EGCG and resveratrol on survival of probiotics encapsulated in 3D printed custard cream during storage, heating, and simulated gastrointestinal conditions were investigated. The addition of bioactives and probiotic coacervates didn't exhibit great influence on the emulsion structure, gel-like rheological behavior and great printing properties of the resulting custard cream samples. The cell survival of encapsulated probiotics in the custard cream with bioactives was prominently increased during storage at 4 °C as well as under heating at 63 and 75 °C. The co-encapsulation of probiotics, EGCG and resveratrol in the custard cream improved the viability of probiotic in the gastrointestinal tract. There was only a 0.85 log and 1.52 log loss of probiotic viability in the custard cream after digestion in simulated gastric and small intestinal digestion conditions. Meanwhile, EGCG and resveratrol in this sample showed a maximum release after simulated digestion, which reached 68.10% and 71.69% release at the end of digestion. Therefore, the co-encapsulation of EGCG, resveratrol with probiotic in this 3D printable custard cream delivery system would be an efficient approach to simultaneous delivery bioactives and probiotic in the gastrointestinal tract with synergistic beneficial effects.

Potential protective function of green tea polyphenol EGCG against high glucose-induced cardiac injury and aging

Green tea and its active extracts have been widely used in a variety of dietary supplements. However, to date, the interaction of these bioactive compounds in green tea and their protein targets are not well studied. We first used the bioinformatics analysis of the relevant diabetes-related targets with the green tea bioactive compounds target proteins to construct a protein interaction (PPI) network to screen the core targets. The results of in vitro experiments showed that EGCG, a major polyphenolic component of green tea, inhibited HG-induced cardiomyocyte hypertrophy, inflammation, oxidative stress response, and cellular senescence. It was found that the PPARG-dependent pathways were involved in the protective effects of EGCG against HG-induced myocardial injury and senescence. This study comprehensively explored the role of EGCG in high glucose-induced myocardial cell injury and aging.

Effects of epigallocatechin-3-gallate on oxidative stress, inflammation, and bone loss in a rat periodontitis model

Background/purposeEpigallocatechin-3-gallate (EGCG) is playing an increasingly important role in the treatment of oral diseases. However, its mechanisms remain to be clarified. This study aimed to investigate the effect of EGCG on oxidative and inflammatory stress and bone loss in experimental periodontitis. Materials and methodsPeriodontitis was induced in rats, followed by gavage using different concentrations of EGCG for 5 weeks. The levels of interleukin-1β (IL-1β), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) in rats were measured. The degree of alveolar bone loss and the number of inflammatory cells were detected. The integrated optical density of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), NLR pyrin domain-containing 3 (NLRP3) and nuclear factor-kappaB p65 (NF-κB p65) was measured. ResultsEGCG (200 mg/kg) significantly reduced alveolar bone loss in the ligated maxillary molars and the number of inflammatory cells in the EGCG-200 group compared with the periodontitis, EGCG-100 and EGCG-400 groups. 200 mg/kg was the optimal dose of EGCG and was used in subsequent experiments. The expression levels of IL-1β, IL-18, TNF-α and MDA were significantly lower and the expression level of SOD was significantly higher in the EGCG-200 group compared with the periodontitis group. The expression of NLRP3 and NF-κB p65 was significantly decreased, while the expression of Nrf2 and HO-1 was significantly increased in the EGCG-200 group compared with the periodontitis group. ConclusionThese results suggest that EGCG inhibits oxidative stress and inflammatory responses in the periodontitis model by modulating the Nrf2/HO-1/NLRP3/NF-κB p65 signaling pathway, thereby decreasing alveolar bone loss.

Epigallocatechin gallate restores the reduction of protein phosphatase 2 A subunit B caused by middle cerebral artery occlusion

BackgroundEpigallocatechin gallate (EGCG) is a flavonoid compound commonly found in green tea. It exhibits antioxidant, anti-inflammatory, and neuroprotective effects in cerebral ischemia. Protein phosphatase 2 A (PP2A) is an important serine/threonine phosphatase enzyme involved in various cellular activities. PP2A subunit B is present abundantly in the brain and plays an important role in the nervous system. We investigated the effect of EGCG on the expression level of PP2A subunit B in cerebral ischemia caused by middle cerebral artery occlusion (MCAO). EGCG (50 mg/kg) or vehicle was injected into the peritoneal cavity prior to MCAO surgery. Neurological behavior tests were performed 24 h after MCAO, and right cerebral cortex tissue was collected. Cerebral ischemia caused serious neurological abnormalities, which were alleviated by EGCG administration. We screened the expression of PP2A subunits containing A, B, and C using reverse-transcription PCR. We confirmed that PP2A subunit B exhibited significant changes in MCAO animals compared to subunits A and C. We continuously examined the expression of PP2A subunit B protein in MCAO animals using Western blot analysis.ResultsEGCG alleviated the reduction of PP2A subunit B protein by MCAO damage. In addition, immunohistochemistry demonstrated a decrease in the number of PP2A subunit B-positive cells in the cerebral cortex, and EGCG attenuated this decrease. Maintenance of PP2A subunit B is important for normal brain function.ConclusionTherefore, our findings suggest that EGCG exerts neuroprotective effects against cerebral ischemia through modulation of PP2A subunit B expression.

In vitro antibacterial activity of green tea-loaded chitosan nanoparticles on caries-related microorganisms and dentin after Er:YAG laser caries removal.

This study aimed to determine the inhibitory effects of green tea (Gt), EGCG, and nanoformulations containing chitosan (Nchi) and chitosan+green tea (Nchi+Gt) against Streptococcus mutans and Lactobacillus casei. In addition, the antibacterial effect of nanoformulations was evaluated directly on dentin after the selective removal of carious lesion. At first, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against S. mutans and L. casei isolates were investigated. In parallel, dentin specimens were exposed to S. mutans to induce carious lesions. Soft dentin was selectively removed by Er:YAG laser (n=33) or bur (n=33). Remaining dentin was biomodified with Nchi (n=11) or Gt+Nchi (n=11). Control group (n=11) did not receive any treatment. Dentin scraps were collected at three time points. Microbiological analyses were conducted and evaluated by agar plate counts. Gt at 1:32 dilution inhibited S. mutans growth while 1:16 was efficient against L. casei. EGCG at 1:4 dilution completely inhibited S. mutans and L. casei growth. Independently of the association with Gt, Nchi completely inhibited S. mutans at 1:4 dilution. For L. casei, different concentrations of Nchi (1:32) and Nchi+Gt (1:8) were required to inhibit cell growth. After selective carious removal, viability of S. mutans decreased (p<0.001), without difference between bur and Er:YAG laser (p>0.05). Treatment with Nchi and Nchi+Gt did not influence the microbial load of S. mutans on dentin (p>0.05). Although variations in concentrations were noticed, all compounds showed antibacterial activity against S. mutans and L. casei. Both bur and Er:YAG laser have effectively removed soft dentin and reduced S. mutans counts. Nanoformulations did not promote any additional antibacterial effect in the remaining dentin.

Soluble dietary fibres decrease α-glucosidase inhibition of epigallocatechin gallate through affecting polyphenol-enzyme binding interactions

The effects of soluble dietary fibres (SDFs) on α-glucosidase inhibition of EGCG were studied. Three arabinoxylans and polygalacturonic acid (PGA) significantly decreased inhibitory activity of EGCG against α-glucosidase, while two β-glucans hardly affected the inhibition. Although arabinoxylans and PGA weakened the competitive inhibition character of EGCG, they maintained the fluorescence quenching effect of EGCG. Then, arabinoxylans and PGA significantly decreased the particle size and turbidity of EGCG-enzyme complex. These results suggest that there formed SDFs-EGCG-enzyme ternary complexes. The stronger decreasing-effects of arabinoxylans and PGA on α-glucosidase inhibition of EGCG than β-glucans resulted from the stronger non-covalent interactions of arabinoxylans and PGA with EGCG. This is considered to arise from the short-branches of arabinoxylans that provided more opportunity for capturing EGCG, and from the strong polarity of PGA carboxyl that promoted hydrogen bondings with EGCG. Conclusively, SDFs should be considered as an impact factor when evaluating α-glucosidase inhibition of dietary polyphenols.

Study on the inhibitory mechanism of dehydrogenated antioxidants on coal spontaneous combustion

In order to comprehensively and systematically analyze the reasons why antioxidant inhibitors can scavenge free radicals in coal and inhibit coal spontaneous combustion, this paper studies the effects of VC, TBHQ, EGCG and BHT on coal spontaneous combustion by means of coal spontaneous combustion characteristics experiments and quantum chemical simulation methods. The low-temperature oxidation characteristics of coal were studied through temperature-programmed experiments. The results showed that the CO emission of coal samples with antioxidants was significantly lower than that of raw coal. At 170°C, the maximum decrease was 37.74%. Fourier infrared test showed that compared with the coal samples without antioxidant treatment, the adsorption strength of hydroxyl structure and oxygen-containing functional groups of the treated coal samples was significantly reduced. The area percentages of hydroxyl and methylene changed significantly, decreased by 7.14% and 6.46%, respectively. Subsequently, molecular models of four antioxidants were constructed using quantum chemical theory, and their Mulliken charges, BDE values ​and frontier orbitals were calculated according to density functional theory (DFT), and the active sites and inhibition mechanisms of antioxidants were discussed. The results showed that H9 of VC, H33 of EGCG, H1 of TBHQ and H40 of BHT all had strong ability to scavenge oxygen-containing free radicals, and their order of strength was TBHQ > BHT > EGCG > VC. Antioxidant inhibitors mainly reduce the number of active free radicals by removing the peroxide groups in the initial stage of the coal oxygen reaction, and remove the hydroxyl groups to prevent the further spontaneous combustion of coal and inhibit the low temperature oxidation process of coal.

Preparation and characterization of high embedding efficiency epigallocatechin-3-gallate glycosylated nanocomposites

Glycosylated protein nano encapsulation was an efficient encapsulation technology, but its embedding rate for EGCG was not high, and the research on the embedding mechanism was relatively weak. Based on this, this study compared the embedding effect of glycosylated peanut globulin and glycosylated casein on EGCG. The embedding mechanism of EGCG with glycosylated protein was discussed by ultraviolet, fluorescence, infrared and fluorescence microscopy. Results revealed that the highest encapsulation efficiency of EGCG was 93.89 ± 1.11%. The neutral pH value and 0.3 mg/mL EGCG addition amount were suitable for EGCG glycosylated nanocomposites. The hydrogen bond between EGCG hydroxyl group and tyrosine and tryptophan of glycosylated protein is mainly non covalent. The encapsulation effect of EGCG glycosylated nanocomposites could be quenched by changing the polar environment and spatial structure of the group. The fluorescence characteristic and dispersibility of EGCG glycosylated peanut globin were higher than EGCG glycosylated casein. This study might provide a theoretical basis for EGCG microencapsulation technology and EGCG application in tea beverage and liquid tea food systems.

Construction of functional soybean peptide–cyclodextrin carboxylate nanoparticles and their interaction with porcine pancreatic α-amylase

In this study, soybean peptide-succinic acid-modified cyclodextrin (SPT-SACD) nanoparticles (NPs) were successfully fabricated by combining SPT and SACD using an antisolvent precipitation approach. The effects of the average molecular weight of SPT and the SPT/SACD mass ratio on the structure and properties of the SACD-SPT NPs were investigated. Under optimal conditions, the SPT/SACD mass ratio was 2:1, and the SPT average molecular weight was 300 Da. SPT-SACD NPs were prepared under these conditions were spherical and had good uniformity. The particle sizes by DLS of SPT1 (300 Da) /SACD and SPT2 (500 Da) /SACD were in the range of 250–400 nm. The interaction between α-amylase and SPT-SACD NPs was investigated using ultraviolet visible (UV–Vis) absorption, fluorescence, and circular dichroism (CD) spectroscopy. The results of the fluorescence spectra and CD spectroscopy suggested that the presence of SPT-SACD NPs changed the microenvironment of the aromatic amino acid residues, which leads to the change of enzyme protein structure. The SPT-SACD NPs statically quenched the intrinsic fluorescence of the α-amylase by forming a complex with the enzyme. Moreover, the SPT-SACD NPs significantly improved the inhibitory effect of EGCG on α-amylase. The semi-inhibitory concentration (IC50) decreased from 0.324 to 0.248 mg/mL. This study provides an improved understanding of the interaction mechanism between polypeptide-cyclodextrin complexes and digestive enzymes, which may facilitate the design of functional foods.

Injectable chitosan hydrogels tailored with antibacterial and antioxidant dual functions for regenerative wound healing

Herein, an injectable self-healing hydrogel with inherent antibacterial activity was fabricated based on the dynamic covalent bond formation between boronic acid and catechol groups in quaternized chitosan as building blocks in conjunct with the in-situ encapsulation of epigallocatechin-3-gallate (EGCG, a green tea derivative). Benefiting from the catechol groups and therapeutic effect of EGCG, the resulting natural-based injectable hydrogels showed excellent antibacterial and antioxidant dual functions in preventing bacterial infection and scavenging radicals. The hydrogels loaded with EGCG also exhibited good biocompatibility along with contact-active antibacterial activity via a “capture and kill” strategy. The dynamic covalent bonding enables shear-thinning delivery of the gels via syringe, followed by rapid self-healing. Additionally, the in vivo wound healing evaluation in a full-thickness skin defect model revealed the appreciable and regenerative wound healing performance of the hydrogels, demonstrating their great potential as novel wound dressings for wound management.

Systemic H2O2 signaling mediates epigallocatechin-3-gallate-induced cadmium tolerance in tomato

Toxic heavy metal cadmium (Cd) reduces crop yield and threatens human health via the food chain. The bioactive flavonoid ‘Epigallocatechin-3-gallate’ (EGCG) affects plant stress response; however, the function of EGCG in Cd tolerance and the molecular pathways remain largely unknown. Here, we revealed that root application of EGCG alleviated Cd stress in tomato plants. While Cd stress decreased Fv/Fm, ФPSII, photosynthetic rate, root growth, root vitality and biomass accumulation by increasing reactive oxygen species (ROS) accumulation and lipid peroxidation, exogenous EGCG minimized excessive ROS accumulation and oxidative stress by promoting the activity of antioxidant enzymes and redox poise in roots and leaves. Moreover, EGCG induced the transcript of RESPIRATORY BURST OXIDASE HOMOLOG1 (RBOH1) and decreased Cd content and photoinhibition in leaves. Interestingly, similar to EGCG, exogenous H2O2 application also enhanced Cd tolerance; however, the application of an NADPH oxidase inhibitor, diphenyleneiodonium (DPI), aggravated Cd phytotoxicity and attenuated the beneficial effects of EGCG on plant tolerance to Cd stress, suggesting that root applied EGCG-induced expression of RBOH1 and associated H2O2 signaling mediate the EGCG-induced enhanced Cd tolerance. This work elucidates a fundamental mechanism behind EGCG-mediated Cd tolerance and contributes to our existing knowledge of stress resistance properties of EGCG in plants.

EGCG regulated osteolytic microenvironment to enhance the antitumor effect of DOX on orthotopic osteosarcoma

Here, we demonstrated that EGCG could enhance the anti-osteosarcoma effect of DOX in vivo and in vitro. The combination of DOX and EGCG could inhibit the activity of osteoclasts at the tumor-bone interface, thereby preventing tumor-induced osteolysis and blocking the vicious circle. Taken together, EGCG may be used as an adjuvant chemotherapy drug to treat osteosarcoma. • EGCG enhanced DOX-induced proliferation inhibition of 143B Cells. • EGCG in synergy with DOX inhibited osteoclast differentiation and bone resorption in vitro. • EGCG in synergy with DOX inhibited AKT phosphorylation in 143B cells and BMMs. • EGCG could enhance the anti-osteosarcoma and anti- osteolysis effect of DOX in vivo. Osteosarcoma is the most common malignant bone tumor with the pathological essence of osteolysis. Doxorubicin (DOX) is common in adjuvant chemotherapy of osteosarcoma. However, it is required to address the conflict between enhancing its dose to improve efficacy and reducing its complications and chemotherapy resistance. Previous studies have demonstrated that EGCG has an antitumor and osteoclastogenesis inhibition effect. However, the combined effect of EGCG and DOX on osteosarcoma is still unclear. Here, EGCG was demonstrated to enhance the 143B cell proliferation inhibition and anti-osteoclastogenesis effect of DOX in vitro. The results suggest that EGCG in synergy with DOX inhibited AKT phosphorylation, which was involved in 143B cells proliferation and osteoclastogenesis. In vivo, the combination of DOX and EGCG could reduce tumor volume and osteolysis destruction compared with the DOX treatment group. This present study raised the possibility that EGCG may be used as an adjuvant chemotherapy drug to treat osteosarcoma.

Neuroprotective effects of catechins in an experimental Parkinson’s disease model and SK-N-AS cells: evaluation of cell viability, anti-inflammatory and anti-apoptotic effects

ABSTRACT Objectives The aim of the study was to establish an in vitro Parkinson’s disease (PD) model and to investigate the cell viability, anti-inflammatory, anti-apoptotic and neuroprotective effects of catechin and EGCG in SK-N-AS and in vitro PD model cells. Method SK-N-AS human neuroblastoma cells were used. To develop an in vitro PD model, SK-N-AS cells were exposed to 6-hydroxydopamine. Model control was performed after ELISA analysis of dopamine and α-synuclein levels in the culture medium. Catechin and EGCG were administered to SK-N-AS and in vitro PD model cells. Cell viability was measured using MTT assay and trypan blue staining. Anti-inflammatory and anti-apoptotic activities of catechin and EGCG were investigated by indirect immunocytochemistry using anti-TNF-α, anti-IL-1β and anti-caspase-3. Results After 24 hours of 6-hydroxydopamine administration at 50 μM, higher αlfa-synuclein and lower dopamine levels were found in PD model than SK-N-AS cells. Cell viability was similar between SK-N-AS and in vitro PD model cells. Treatment with both bioactive components increased cell viability of in vitro PD model cells. Caspase-3 immunoreactivity was significantly reduced in SK-N-AS and PD model cells after EGCG administration, while it was decreased only in PD model cells after catechin administration. IL-1β staining intensity weakened after catechin administration in PD model cells, after EGCG administration in SK-N-AS cells. TNF-α staining intensity was similar in both cells. Conclusion Catechin and EGCG increased cell viability in PD model neuron cells. Both components showed anti-apoptotic and anti-inflammatory effects. Catechin may be more effective in preventing damage to neurons PD.

Effects of tea polyphenols and EGCG on glucose metabolism and intestinal flora in diabetic mice fed a cornstarch-based functional diet

Diabetes is a worldwide metabolic diseases that requires adjustments in the blood glucose. Cornstarch is one kind of resistant starch, which helps to control postprandial glucose, and is a desired alternatives of carbohydrates for developing functional food. Herein, a cornstarch-based functional diet (CFD) was developed, and in this study we investigated the effects of CFD supplemented with tea polyphenols and EGCG on blood glucose and intestinal flora in diabetic mice. The results showed that diabetic mice had significant weight loss and serious hyperglycemia. The CFD or CFD supplemented with tea polyphenols and EGCG resulted in a trend toward reduced fasting blood glucose. Furthermore, diabetes had significant intestinal flora disturbance, with particularly increased levels of Bacteroidaceae, Helicobacteraceae, Ruminococcaceae, Enterobacteriaceae, Rikenellaceae and Saccharibacteria_genera_incertae_sedis, and decreased Prevotellaceae, Coriobacteriaceae, Bifidobacteriaceae and Verrucomicrobiaceae. Interesting, CFD supplemented with EGCG significantly increased levels of Prevotellaceae and Coriobacteriaceae, and decreased Lachnospiraceae, Helicobacteraceae, Ruminococcaceae and Saccharibacteria_genera_incertae_sedis compared to controls. CFD supplemented with tea polyphenols significantly increased the Coriobacteriaceae and Bifidobacteriaceae. The comprehensive analysis indicated that tea polyphenols and EGCG supplementation improved glucose metabolism, and reversed the sick changes of intestinal flora, suggesting they are two valuable additions to promote nutritional value of CFD.