Epigallocatechin-3-gallate protects bovine ruminal epithelial cells against lipopolysaccharide-induced inflammatory damage by activating autophagy.

BACKGROUND: Subacute ruminal acidosis (SARA) causes an increase in endotoxin, which can induce immune and inflammatory responses in the ruminal epithelium of dairy cows. In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against SARA-induced inflammation and the underlying mechanisms are unknown. RESULTS: In vivo, eight ruminally cannulated Holstein cows in mid-lactation were randomly assigned to either a low-concentrate (40%) diet (CON) or a high-concentrate (60%) diet (HC) for 3 weeks to induce SARA (n = 4). Cows with SARA had greater serum concentrations of tumor necrosis factor (TNF)-α and interleukin-6, and epithelium had histological signs of damage. In vitro, immortalized bovine ruminal epithelial cells (BREC) were treated with lipopolysaccharide (LPS) to imitate the inflammatory damage caused by SARA. Our data revealed that BREC treated with 10 µg/mL LPS for 6 h successfully induce a robust inflammatory response as indicated by increased phosphorylation of IκBα and nuclear factor kappa-B (NF-κB) p65. Pre-treatment of BREC with 50 µmol/L EGCG for 6 h before LPS challenge promoted the degradation of NLR family pyrin domain containing 3 (NLRP3) inflammasome through activation of autophagy, which further repressed activation of NF-κB pathway targeting Toll-like receptor 4 (TLR4). Analyses also revealed that the ECGG upregulated tight junction (TJ) protein expression upon incubation with LPS. CONCLUSIONS: Subacute ruminal acidosis causes ruminal epithelium injury and systemic inflammation in dairy cows. However, the anti-inflammatory effects of EGCG help preserve the integrity of the epithelial barrier through activating autophagy when BREC are exposed to LPS. Thus, EGCG could potentially serve as an effective therapeutic agent for SARA-associated inflammation.

Neurodegenerative diseases and catechins: (-)-epigallocatechin-3-gallate is a modulator of chronic neuroinflammation and oxidative stress.

Catechins, a class of phytochemicals found in various fruits and tea leaves, have garnered attention for their diverse health-promoting properties, including their potential in combating neurodegenerative diseases. Among these catechins, (-)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, has emerged as a promising therapeutic agent due to its potent antioxidant and anti-inflammatory effects. Chronic neuroinflammation and oxidative stress are key pathological mechanisms in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). EGCG has neuroprotective efficacy due to scavenging free radicals, reducing oxidative stress and attenuating neuroinflammatory processes. This review discusses the molecular mechanisms of EGCG's anti-oxidative stress and chronic neuroinflammation, emphasizing its effects on autoimmune responses, neuroimmune system interactions, and focusing on the related effects on AD and PD. By elucidating EGCG's mechanisms of action and its impact on neurodegenerative processes, this review underscores the potential of EGCG as a therapeutic intervention for AD, PD, and possibly other neurodegenerative diseases. Overall, EGCG emerges as a promising natural compound for combating chronic neuroinflammation and oxidative stress, offering novel avenues for neuroprotective strategies in the treatment of neurodegenerative disorders.

Effects of Green Tea Extract Epigallocatechin-3-Gallate on Oral Diseases: A Narrative Review.

OBJECTIVES: Oral diseases are among the most prevalent diseases globally. Accumulating new evidence suggests considerable benefits of epigallocatechin-3-gallate (EGCG) for oral health. This review aims to explore the role and application of EGCG in main oral diseases. METHODS: This narrative review thoroughly examines and summarizes the most recent literature available in scientific databases (PubMed, Web of Science, Scopus, and Google Scholar) reporting advances in the role and application of EGCG within the dental field. The major keywords used included "EGCG", "green tea extract", "oral health", "caries", "pulpitis", "periapical disease", "periodontal disease", "oral mucosa", "salivary gland", and "oral cancer". CONCLUSIONS: EGCG prevents and manages various oral diseases through its antibacterial, anti-inflammatory, antioxidant, and antitumor properties. Compared to traditional treatments, EGCG generally exhibits lower tissue irritation and positive synergistic effects when combined with other therapies. Novel delivery systems or chemical modifications can significantly enhance EGCG's bioavailability, prolong its action, and reduce toxicity, which are current hotspots in developing new materials. CLINICAL SIGNIFICANCE: this review provides an exhaustive overview of the biological activities of EGCG to major oral diseases, alongside an exploration of applications and limitations, which serves as a reference for preventing and managing oral ailments.

Soy protein isolate ameliorate gel properties by regulating the non-covalent interaction between epigallocatechin-3-gallate and myofibrillar protein.

This study primarily investigated the improvement of high-dose Epigallocatechin-3-Gallate (EGCG)-induced deterioration of MP gel by soy protein isolate (SPI) addition. The results showed that EGCG could interact with MP, SPI, and HSPI (heated), indicating the competitive ability of SPI/HSPI against EGCG with MP. EGCG was encapsulated by SPI/HSPI with high encapsulation efficiency and antioxidation, with antioxidant activities of 78.5% âˆ¼ 79.2%. FTIR and molecular docking results revealed that MP, SPI, and HSPI interacted with EGCG through hydrogen bonding and hydrophobic interactions. SPI/HSPI competed with MP for EGCG, leading to the restoration of MHC and Actin bands, alleviating the aggregation caused by EGCG and oxidation. Additionally, SPI/HSPI-E significantly reduced the high cooking loss (23.71 and 26.65%) and gel strength (13.60 and 17.02%) induced by EGCG. Hence, SPI competed with MP for EGCG binding site to ameliorate MP gel properties, thereby alleviating the detrimental changes in MP caused by high-dose EGCG and oxidation.

Epigallocatechin Gallate Derivative Y6 Reverses Oxaliplatin Resistance in Hepatocellular Carcinoma via Targeting the MiR-338-3p/HIF-1α/TWIST Axis to Inhibit EMT.

BACKGROUND: The emergence of drug resistance to oxaliplatin (OXA) is one of the critical obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate the effect of Y6 on oxaliplatin resistance in HCC. METHODS: MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant cells and observed the morphological changes of the cells. At the same time, transwell assay was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and Western blot analysis were performed to determine the expression levels of the miR-338-3p gene, HIF-1α/Twist proteins, and EMT-related proteins. RESULTS: We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the control group and OXA group showed typical mesenchymal-like cell morphology, while most of the cells in co-administration groups showed typical epithelioid cell morphology, and the ability of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated. CONCLUSION: Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT. Therefore, Y6 could be considered an effective medication resistance reversal agent, which could improve the therapeutic effect for hepatocellular cancer patients.

Analysis of the Antimicrobial Activity of Epigallocatechin-3-Gallate (EGCG).

We studied antimicrobial activity of epigallocatechin-3-gallate (EGCG), a green tea polyphenolic catechin, and its combined use with ceftazidime (CAZ) against bacterial strains of Klebsiella pneumoniae. EGCG exhibited no activity against strains of K. pneumoniae with a different sensitivity to CAZ. However, for a "sensitive" strain, a decrease in minimum inhibitory concentration (MIC) of CAZ (from 0.064 to 0.023 mg/liter) was revealed when CAZ was co-administered with EGCG. For a "resistant" stain, MIC of CAZ remained high, but activation of EGCG at its high concentrations was observed. Indirect evidence of antimicrobial effect of EGCG co-administered with CAZ on Klebsiella was obtained.

Epigallocatechin-3-gallate adsorbed on core-shell gold nanorod@mesoporous silica nanoparticles, an antioxidant nanomaterial with photothermal properties.

Epigallocatechin-3-gallate (EGCG) exhibits several pharmacological activities with potential benefits for human health, however, it has low oral bioavailability. A promising approach is to transport EGCG in a nanostructured system to protect it until it reaches the site of action and also allow combining chemotherapy with phototherapy to improve its therapeutic efficiency. The aim of this work was to synthesize GNR@mSiO2-NH2/EGCG and characterize the adsorption process, its antioxidant activity, properties and photothermal stability, for its potential use in chemo-photothermal therapy. The nanosystem presented good encapsulation efficiency (19.2 %) and EGCG loading capacity (6.0 %). The DPPH• free radical scavenging capacity (RSA) and chelating activity of the nanosystem was 60.7 ± 6.9 % and 71.0 ± 6.4 % at an EGCG equivalent concentration of 1 µg/mL and 30 µg/mL, respectively. The core-shell NPs presented a good photothermal transduction efficiency of 17 %. EGCG free, as well as its RSA and chelating activity, remained stable after NIR irradiation (808 nm, 7 W/cm2). The morphology of GNR@mSiO2 remained intact after being irradiated with NIR, however, ultrasmall gold NPs could be observed, probably a product of photocracking of GNR. In summary, the nanosystem has good antioxidant activity, photothermal stability, and photothermal transduction ability making it potentially useful for chemo-photothermal therapy.

Natural products targeting amyloid-ß oligomer neurotoxicity in Alzheimer's disease.

Alzheimer's disease (AD) constitutes a major global health issue, characterized by progressive neurodegeneration and cognitive impairment, for which no curative treatment is currently available. Current therapeutic approaches are focused on symptom management, highlighting the critical need for disease-modifying therapy. The hallmark pathology of AD involves the aggregation and accumulation of amyloid-ß (Aß) peptides in the brain. Consequently, drug discovery efforts in recent decades have centered on the Aß aggregation cascade, which includes the transition of monomeric Aß peptides into toxic oligomers and, ultimately, mature fibrils. Historically, anti-Aß strategies focused on the clearance of amyloid fibrils using monoclonal antibodies. However, substantial evidence has highlighted the critical role of Aß oligomers (AßOs) in AD pathogenesis. Soluble AßOs are now recognized as more toxic than fibrils, directly contributing to synaptic impairment, neuronal damage, and the onset of AD. Targeting AßOs has emerged as a promising therapeutic approach to mitigate cognitive decline in AD. Natural products (NPs) have demonstrated promise against AßO neurotoxicity through various mechanisms, including preventing AßO formation, enhancing clearance mechanisms, or converting AßOs into non-toxic species. Understanding the mechanisms by which anti-AßO NPs operate is useful for developing disease-modifying treatments for AD. In this review, we explore the role of NPs in mitigating AßO neurotoxicity for AD drug discovery, summarizing key evidence from biophysical methods, cellular assays, and animal models. By discussing how NPs modulate AßO neurotoxicity across various experimental systems, we aim to provide valuable insights into novel therapeutic strategies targeting AßOs in AD.

Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile.

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

Epigallocatechin-3-gallate attenuates fluoride induced apoptosis via PI3K/FoxO1 pathway in ameloblast-like cells.

Fluoride is a double-edged sword. It was widely used for early caries prevention while excessive intake caused a toxicology effect, affected enamel development, and resulted in dental fluorosis. The study aimed to evaluate the protective effect and mechanism of Epigallocatechin-3-gallate (EGCG) on the apoptosis induced by fluoride in ameloblast-like cells. We observed that NaF triggered apoptotic alterations in cell morphology, excessive NaF arrested cell cycle at the G1, and induced apoptosis by up-regulating Bax and down-regulating Bcl-2. NaF activated the insulin-like growth factor receptor (IGFR), and phosphatidylinositol-3-hydroxylase (p-PI3K), while dose-dependently down-regulating the expression of Forkhead box O1 (FoxO1). EGCG supplements reversed the changes in LS8 morphology, the cell cycle, and apoptosis induced by fluoride. These results indicated that EGCG possesses a protective effect against fluoride toxicity. Furthermore, EGCG suppressed the activation of p-PI3K and the down-regulation of FoxO1 caused by fluoride. Collectively, our findings suggested that EGCG attenuated fluoride-induced apoptosis by inhibiting the PI3K/FoxO1 signaling pathway. EGCG may serve as a new alternative method for dental fluorosis prevention, control, and treatment.

Epigallocatechin-3-gallate Inhibits LPS/AßO-induced Neuroinflammation in BV2 Cells through Regulating the ROS/TXNIP/NLRP3 Pathway.

Neuroinflammation is a key factor in cognitive dysfunction and neurodegenerative diseases such as Alzheimer's disease (AD), so inhibiting neuroinflammation is considered as a potential treatment for AD. Epigallocatechin-3-gallate (EGCG), a polyhydroxyphenol of green tea, has been found to exhibit anti-oxidative, anti-inflammatory and neuroprotective effects. The aim of this study was to investigate the inhibitory effect of EGCG on inflammation and its mechanism. In this study, BV2 cells were simultaneously exposed to lipopolysaccharides (LPS) and the amyloid-ß oligomer (AßO) to induce inflammatory microenvironments. Inflammatory cytokines and NLRP3 inflammasome-related molecules were detected by RT-PCR and Western Blot. The results show that EGCG inhibits LPS/AßO-induced inflammation in BV2 cells through regulating IL-1ß, IL-6, and TNF-α. Meanwhile, EGCG reduces the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and levels of intracellular ROS in BV2 cells treated with LPS/AßO by affecting the mitochondrial membrane potential (MMP). Further research found that EGCG inhibited MMP through regulating thioredoxin-interacting protein (TXNIP) in LPS/AßO-induced neuroinflammation. In conclusion, EGCG may alleviate LPS/AßO-induced microglial neuroinflammation by suppressing the ROS/ TXNIP/ NLRP3 pathway. It may provide a potential mechanism underlying the anti-inflammatory properties of EGCG for alleviating AD.

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.

Epigallocatechin-3-gallate ameliorates lipopolysaccharide-induced acute thymus involution in mice via AMPK/Sirt1 pathway.

The thymus, a site to culture the naïve T lymphocytes, is susceptible to atrophy or involution due to aging, inflammation, and oxidation. Epigallocatechin-3-gallate (EGCG) has been proven to possess anti-inflammatory, antioxidant, and antitumor activity. Here, we investigate the effects of EGCG on thymic involution induced by lipopolysaccharide (LPS), an endotoxin derived from Gram-negative bacteria. The methodology included an in vivo experiment on female Kunming mice exposed to LPS and EGCG. Morphological assessment of thymic involution, immunohistochemical detection, and thymocyte subsets analysis by flow cytometry were further carried out to evaluate the potential role of EGCG on the thymus. As a result, we found that EGCG alleviated LPS-induced thymic atrophy, increased mitochondrial membrane potential and superoxide dismutase levels, and decreased malondialdehyde and reactive oxygen species levels. In addition, EGCG pre-supplement restored the ratio of thymocyte subsets, the expression of autoimmune regulator, sex-determining region Y-box 2, and Nanog homebox, and reduced the number of senescent cells and collagen fiber deposition. Western blotting results indicated that EGCG treatment elevated LPS-induced decrease in pAMPK, Sirt1 protein expression. Collectively, EGCG relieved thymus architecture and function damaged by LPS via regulation of AMPK/Sirt1 signaling pathway. Our findings may provide a new strategy on protection of thymus from involution caused by LPS by using EGCG. And EGCG might be considered as a potential agent for the prevention and treatment of thymic involution.

Epigallocatechin-3-gallate inhibits osteogenic differentiation of vascular smooth muscle cells through the transcription factor JunB.

Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.

Epigallocatechin-3-gallate Alleviates Ethanol-Induced Endothelia Cells Injury Partly through Alteration of NF-κB Translocation and Activation of the Nrf2 Signaling Pathway.

Ethanol (alcohol) is a risk factor that contributes to non-communicable diseases. Chronic abuse of ethanol is toxic to both the heart and overall health, and even results in death. Ethanol and its byproduct acetaldehyde can harm the cardiovascular system by impairing mitochondrial function, causing oxidative damage, and reducing contractile proteins. Endothelial cells are essential components of the cardiovascular system, are highly susceptible to ethanol, either through direct or indirect exposure. Thus, protection against endothelial injury is of great importance for persons who chronic abuse of ethanol. In this study, an in vitro model of endothelial injury was created using ethanol. The findings revealed that a concentration of 20.0 mM of ethanol reduced cell viability and Bcl-2 expression, while increasing cell apoptosis, intracellular reactive oxygen species (ROS) levels, mitochondrial depolarization, and the expression of Bax and cleaved-caspase-3 in endothelial cells. Further study showed that ethanol promoted nuclear translocation of nuclear factor kappa B (NF-κB), increased the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 in the culture medium, and inhibited nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway. The aforementioned findings suggest that ethanol has a harmful impact on endothelial cells. Nevertheless, the application of epigallocatechin-3-gallate (EGCG) to the cells can effectively mitigate the detrimental effects of ethanol on endothelial cells. In conclusion, EGCG alleviates ethanol-induced endothelial injury partly through alteration of NF-κB translocation and activation of the Nrf2 signaling pathway. Therefore, EGCG holds great potential in safeguarding individuals who chronically abuse ethanol from endothelial dysfunction.

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

Excessive macroautophagy/autophagy leads to pancreatic ß-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 ß-cell-specific NR3C1 overexpression mice in vivo and NR3C1-enhanced ß cells in vitro. We showed that EGCG protects pancreatic ß 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 ß cells, which alleviates oxidative stress, and thereby prevents excessive autophagy. Moreover, FTO overexpression abolishes the beneficial effects of EGCG on ß cells against NR3C1 enhancement-induced damage. Collectively, our results demonstrate that EGCG protects pancreatic ß 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; ßNR3C1 mice: pancreatic ß-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.

Biosynthesis of Nanoparticles with Green Tea for Inhibition of ß-Amyloid Fibrillation Coupled with Ligands Analysis.

Background: Inhibition of amyloid ß protein fragment (Aß) aggregation is considered to be one of the most effective strategies for the treatment of Alzheimer's disease. (-)-Epigallocatechin-3-gallate (EGCG) has been found to be effective in this regard; however, owing to its low bioavailability, nanodelivery is recommended for practical applications. Compared to chemical reduction methods, biosynthesis avoids possible biotoxicity and cumbersome preparation processes. Materials and Methods: The interaction between EGCG and Aß42 was simulated by molecular docking, and green tea-conjugated gold nanoparticles (GT-Au NPs) and EGCG-Au NPs were synthesized using EGCG-enriched green tea and EGCG solutions, respectively. Surface active molecules of the particles were identified and analyzed using various liquid chromatography-tandem triple quadrupole mass spectrometry methods. ThT fluorescence assay, circular dichroism, and TEM were used to investigate the effect of synthesized particles on the inhibition of Aß42 aggregation. Results: EGCG as well as apigenin, quercetin, baicalin, and glutathione were identified as capping ligands stabilized on the surface of GT-Au NPs. They more or less inhibited Aß42 aggregation or promoted fibril disaggregation, with EGCG being the most effective, which bound to Aß42 through hydrogen bonding, hydrophobic interactions, etc. resulting in 39.86% and 88.50% inhibition of aggregation and disaggregation effects, respectively. EGCG-Au NPs were not as effective as free EGCG, whereas multiple thiols and polyphenols in green tea accelerated and optimized heavy metal detoxification. The synthesized GT-Au NPs conferred the efficacy of diverse ligands to the particles, with inhibition of aggregation and disaggregation effects of 54.69% and 88.75%, respectively, while increasing the yield, enhancing water solubility, and decreasing cost. Conclusion: Biosynthesis of nanoparticles using green tea is a promising simple and economical drug-carrying approach to confer multiple pharmacophore molecules to Au NPs. This could be used to design new drug candidates to treat Alzheimer's disease.

Epigallocatechin-3-gallate attenuates the sulfamethoxazole-induced immunotoxicity and reduces SMZ residues in Procambarus clarkii.

Sulfamethoxazole (SMZ) is a commonly used antibiotic in aquaculture, and its residues in water bodies pose a significant threat to aquatic organisms in the water environment. In the present study, epigallocatechin-3-gallate (EGCG), a catecholamine, was used to mitigate the immunotoxicity caused by SMZ exposure in Procambarus clarkii. EGCG reduced the apoptosis rate, which was elevated by SMZ exposure, and increased the total hemocyte count. Simultaneously, EGCG enhanced the activities of enzymes related to antibacterial and antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), lysozyme (LZM), acid phosphatase (ACP), and GSH, which were decreased following SMZ exposure. Hepatopancreatic histology confirmed that EGCG ameliorated SMZ-induced tissue damage caused by SMZ exposure. In addition to EGCG attenuating SMZ-induced immunotoxicity in crayfish, we determined that EGCG can effectively reduce SMZ residues in crayfish exposed to SMZ. In addition, at the genetic level, the expression levels of genes related to the immune response in hemocytes were disrupted after SMZ exposure, and EGCG promoted their recovery and stimulated an increase in the expression levels of metabolism-related transcripts in hemocytes. The transcriptome analysis was conducted, and "phagosome" and "apoptosis" pathways were shown to be highlighted using Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. To the best of our knowledge, this is the first study to confirm that EGCG attenuates SMZ-induced immunotoxicity in aquatic animals and reduces SMZ residues in aquatic animals exposed to SMZ. Our study contributes to the understanding of the mechanisms by which EGCG reduces the immunotoxicity of antibiotic residues in aquatic animals.

Antibacterial Activity of Epigallocatechin-3-gallate (EGCG) Loaded Lipid-chitosan Hybrid Nanoparticle against Planktonic Microorganisms.

Epigallocatechin-3-gallate (EGCG), a polyphenol derived from Green Tea, is one of the sources of natural bioactive compounds which are currently being developed as medicinal ingredients. Besides other biological activities, this natural compound exhibits anti-cariogenic effects. However, EGCG has low physical-chemical stability and poor bioavailability. Thus, the purpose of this study was to develop and characterize lipid-chitosan hybrid nanoparticle with EGCG and to evaluate its in vitro activity against cariogenic planktonic microorganisms. Lipid-chitosan hybrid nanoparticle (LCHNP-EGCG) were prepared by emulsion and sonication method in one step and characterized according to diameter, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (EE), mucoadhesion capacity and morphology. Strains of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus casei were treated with LCHNP- EGCG, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated. LCHNP-EGCG exhibited a size of 217.3 ± 5.1 nm with a low polydispersity index (0.17) and positive zeta potential indicating the presence of chitosan on the lipid nanoparticle surface (+33.7 mV). The LCHNP-EGCG showed a spherical morphology, high stability and a mucoadhesive property due to the presence of chitosan coating. In addition, the EGCG encapsulation efficiency was 96%. A reduction of almost 15-fold in the MIC and MBC against the strains was observed when EGCG was encapsulated in LCHNP, indicating the potential of EGCG encapsulation in lipid-polymer hybrid nanoparticles. Taking the results together, the LCHNP-EGCG could be an interesting system to use in dental care due to their nanometric size, mucoadhesive properties high antibacterial activity against relevant planktonic microorganisms.

EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness.

Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis. Given that LIN28B acts by negatively regulating the biogenesis of the tumor suppressor let-7 miRNAs, we reasoned that selective interference with the LIN28B/let-7 miRNA interaction would increase let-7 miRNA levels, ultimately leading to reduced NB aggressiveness. Here, we selected (-)-epigallocatechin 3-gallate (EGCG) out of 4959 molecules screened as the molecule with the best inhibitory activity on LIN28B/let-7 miRNA interaction and showed that treatment with PLC/PLGA-PEG nanoparticles containing EGCG (EGCG-NPs) led to an increase in mature let-7 miRNAs and a consequent inhibition of NB cell growth. In addition, EGCG-NP pretreatment reduced the tumorigenic potential of NB cells in vivo. These experiments suggest that the LIN28B/let-7 miRNA axis is a good therapeutic target in NB and that EGCG, which can interfere with this interaction, deserves further preclinical evaluation.