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Abstract (−)-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.

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.

Dorsal root injury usually leads to irreversible sensory function loss and lacks effective treatments. (−)-epigallocatechin-3-gallate (EGCG) is reported to exert neuroprotective roles in the nervous systems. However, the function of EGCG in treating dorsal root injury remains unclear. Hence, we built the dorsal root crush injury (DRCI) rat model to be treated with EGCG, followed by the western blot, Enzyme-linked immunosorbent assay, and sensory behavior tests. We observed that EGCG can upregulate the Lysine acetyltransferase 6A (KAT6A) level and inhibit the pyroptosis, indicated by downregulated gasdermin-D, caspase-1, and interleukin 18 protein levels, and alleviate the neuropathic pain, indicated by the decreased paw withdraw threshold in Plantar test and decreased paw withdraw latency in von Frey test, and downregulated calcitonin gene-related peptide, nerve growth factor, and c-Fos protein levels. But EGCG cannot alleviate the neuropathic pain when the KAT6A was inhibited by CTX-0124143 and pyroptosis was activated by Miltirone. These combined results indicated that EGCG can promote the sensory function recovery in rats after DRCI via upregulating KAT6A and inhibiting pyroptosis, laying the foundation for EGCG to be a novel candidate for the treatment of dorsal root injury.

Phase transition behaviors of poly(N-isopropylacrylamide) nanogels with different compositions induced by (−)-epigallocatechin-3-gallate (EGCG) and ethyl gallate (EG) has been investigated systematically. Monodisperse poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) (P(NIPAM-co-NMAM)) and poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-co-HEMA)) nanogels with different feeding monomer ratios were prepared by emulsion polymerization. P(NIPAM-co-NMAM) nanogels exhibit rapid isothermal phase transition behavior in EGCG solutions with low concentration (10−3 mol/L) in less than 10 minutes. The thermosensitive phase transition behaviors of nanogels are affected not only by the copolymerized monomers but also by the concentrations of EGCG and EG in aqueous solutions. Nanogels remain in a shrunken state and do not exhibit thermosensitive phase transition behaviors in EGCG solutions (≥5 mmol/L), whereas they display thermo-responsive phase transition behaviors in EG solutions. The volume phase transition temperature (VPTT) shifts to lower temperatures with increasing EG concentration. The diameters of P(NIPAM-co-NMAM) nanogels decrease with increasing EG concentration at temperatures between 29 and 33 °C. In contrast, the diameters of P(NIPAM-co-HEMA) nanogels increase with increasing EGCG concentration at temperatures between 37 and 45 °C. The results demonstrate the potential of nanogels for simple detection of EG and EGCG concentrations in aqueous solutions over a wide temperature range, and EGCG can serve as a signal for the burst-release of drugs from the P(NIPAM-co-NMAM)-based carriers at physiological temperature. [ABSTRACT FROM AUTHOR]

Abstract In this study, complexes formed by sodium caseinate (CS) and different concentrations of (−)‐epigallocatechin‐3‐gallate (EGCG) were successfully prepared. The structures of the CS–EGCG complexes were then analyzed by fluorescence spectroscopy, circular dichroism, and Fourier transform infrared spectroscopy (FTIR). Their thermodynamic features were also analyzed by Van't Hoff equation before evaluating antioxidant properties as well as emulsion stability. The results showed that EGCG grafting significantly altered the CS structure, primarily due to their interactions. However, besides the covalent bonding within CS–EGCG, thermodynamic analysis further highlighted the presence of slight interactions driven by hydrophobic and entropic changes. The EGCG grafting also decreased the surface hydrophobicity of CS while increasing its solubility, thus improving the stability of the protein in water. Finally, the grafting process significantly improved the thermal and emulsifying stability of CS as well as its antioxidant properties, especially 3‐ethylbenzothiazoline‐6‐sulfonic acid and 2,2‐diphenyl‐1‐picrylhydrazyl scavenging properties and ferric ion reducing power. These findings can contribute to the study of protein and polyphenol interactions in food fields.

Natural products have been a bedrock for drug discovery for decades. (−)-Epigallocatechin-3-gallate (EGCG) is one of the widely studied natural polyphenolic compounds derived from green tea. It is the key component believed to be responsible for the medicinal value of green tea. Significant studies implemented in in vitro, in cellulo, and in vivo models have suggested its anti-oxidant, anti-cancer, anti-diabetic, anti-inflammatory, anti-microbial, neuroprotective activities etc. Despite having such a wide array of therapeutic potential and promising results in preclinical studies, its applicability to humans has encountered with rather limited success largely due to the poor bioavailability, poor membrane permeability, rapid metabolic clearance and lack of stability of EGCG. Therefore, novel techniques are warranted to address those limitations so that EGCG or its modified analogs can be used in the clinical setup. This review comprehensively covers different strategies such as structural modifications, nano-carriers as efficient drug delivery systems, synergistic studies with other bioactivities to improve the chemico-biological aspects (e.g., stability, bioavailability, permeability, etc.) of EGCG for its enhanced pharmacokinetics and pharmacological properties, eventually enhancing its therapeutic potentials. We think this review article will serve as a strong platform with comprehensive literature on the development of novel techniques to improve the bioavailability of EGCG so that it can be translated to the clinical applications. [ABSTRACT FROM AUTHOR]

Abstract Cardiomyopathies comprise a group of disorders wherein the primary defect is in cardiac myocytes. The common forms of pediatric cardiomyopathies, classified according to their morphological and functional manifestations, include dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), hypertrophic cardiomyopathy (HCM), and others. Cardiac gene mutations caused abnormal myofibril Ca2+ sensitivity may be involved in the underlying molecular mechanisms of cardiomyopathies. Thus far, no effective treatment for cardiomyopathies has been developed, especially for HCM and RCM in which diastolic dysfunction occurs early and followed by diastolic heart failure. Our laboratory is among the first in the field to investigate the mechanisms underlying various cardiomyopathies and search for the treatment for these disorders. In the past, we and other researchers have found that (−)‐epigallocatechin‐3‐gallate (EGCg), the major biomedical polyphenol extracted from green tea, possess multiple therapeutic effects on protecting cardiac function and correcting impaired relaxation. Given its therapeutic effects, EGCg might be a potential drug candidate for administration to patients with cardiomyopathy and heart failure. In this review, we will discuss the molecular mechanisms associated with the pathogenesis of diastolic dysfunction and summarize the pharmacological effects of EGCg on experimental animals and pediatric patients with cardiomyopathies and diastolic dysfunction.

Phase transition behaviors of poly(N-isopropylacrylamide) nanogels with different compositions induced by (−)-epigallocatechin-3-gallate (EGCG) and ethyl gallate (EG) has been investigated systematically. Monodisperse poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) (P(NIPAM-co-NMAM)) and poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-co-HEMA)) nanogels with different feeding monomer ratios were prepared by emulsion polymerization. P(NIPAM-co-NMAM) nanogels exhibit rapid isothermal phase transition behavior in EGCG solutions with low concentration (10−3 mol/L) in less than 10 minutes. The thermosensitive phase transition behaviors of nanogels are affected not only by the copolymerized monomers but also by the concentrations of EGCG and EG in aqueous solutions. Nanogels remain in a shrunken state and do not exhibit thermosensitive phase transition behaviors in EGCG solutions (≥5 mmol/L), whereas they display thermo-responsive phase transition behaviors in EG solutions. The volume phase transition temperature (VPTT) shifts to lower temperatures with increasing EG concentration. The diameters of P(NIPAM-co-NMAM) nanogels decrease with increasing EG concentration at temperatures between 29 and 33 °C. In contrast, the diameters of P(NIPAM-co-HEMA) nanogels increase with increasing EGCG concentration at temperatures between 37 and 45 °C. The results demonstrate the potential of nanogels for simple detection of EG and EGCG concentrations in aqueous solutions over a wide temperature range, and EGCG can serve as a signal for the burst-release of drugs from the P(NIPAM-co-NMAM)-based carriers at physiological temperature.

(-)-epigallocatechin-3-gallate (EGCG), the main active component of tea polyphenols, has been less studied in Litopenaeus vannamei. Therefore, the potential benefits of EGCG on L. vannamei were explored in this experiment. L. vannamei were fed diets containing EGCG (0, 0.5, and 1.0 g/kg). At the end of the 60-day farming experiment, metabolomics, transcriptomics, quantitative real-time PCR assays, and tissue sections were used to assess and explore the effects of EGCG on growth, antioxidant capacity, and immunity. It was found that the best growth and genes expressions related to antioxidant, anti-stress, apoptosis, and immunity were observed in the group with 0.5 g/kg EGCG. The analysis of hepatopancreatic metabolomics and transcriptomics results revealed bumper differential metabolites and differentially expressed genes (DEGs) associated with nutrient metabolism, digestion, immunity, and environmental adaptation. Many metabolites with anti-inflammatory, antibacterial, antiviral, and antioxidant activities have been identified. A large number of DEGs were enriched in apoptosis, Rap1 signaling pathway, HIF-1 signaling pathway, hippo signaling pathway, chemokine signaling pathway, and signaling pathways related to amino acid and lipid metabolism. In conclusion, dietary 0.5 g/kg EGCG was beneficial for growth, resistance to oxidative stress, and immunity in L. vannamei. The improvement of the properties was attributed to the modulation of signaling pathways, metabolites abundance and genes expressions related to the above properties by EGCG., Competing Interests: Declaration competing of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The effects of nanoparticles (NPs) on microbiota homeostasis and their physiological relevance are still unclear. Herein, we compared the modulation and consequent pharmacological effects of oral administration of (−)-epigallocatechin-3-gallate (EGCG)-loaded β-cyclodextrin (β-CD) NPs (EGCG@β-CD NPs) and EGCG on gut microbiota. EGCG@β-CD NPs were prepared using self-assembly and their influence on the intestinal microbiome structure was analyzed using a metagenomics approach. The "Encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential" of EGCG@β-CD NPs were recorded as 98.27 ± 0.36%, 124.6 nm, 0.313 and –24.3 mV, respectively. Surface morphology of EGCG@β-CD NPs was observed as spherical. Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and molecular docking studies confirmed that EGCG could be well encapsulated in β-CD and formed as EGCG@β-CD NPs. After being continuously administered EGCG@β-CD NPs for 8 weeks, the serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and liver malondialdehyde (MDA) levels in the rats were significantly decreased, while the levels of catalase (CAT) and apolipoprotein-A1 (apo-A1) in the liver increased significantly in the hyperlipidemia model of rats, when compared to the high-fat-diet group. Furthermore, metagenomic analysis revealed that the ratio of Verrucomicrobia/Bacteroidetes was altered and Bacteroidetes decreased in the high-fat diet +200 mg/kg·bw EGCG@β-CD NPs group, while the abundance of Verrucomicrobia was significantly increased, especially Akkermansia muciniphila in rat feces. EGCG@β-CD NPs could be a promising EGCG delivery strategy to modulate the gut microbiota, enhancing its employment in the prevention of hyperlipidemia. [ABSTRACT FROM AUTHOR]

Amyloid-like fibrils derived from plant proteins has provided a strategy to improve plant protein physicochemical performance and has substantial untapped potential for application in stabilizing oil-in-water (O/W) emulsions. This study aimed to explore the structural modifications of lentil protein fibrils (LPF) and their emulsifying properties facilitated by EGCG, with the proposal of potential underlying mechanism. The structure and morphology of LPF-EGCG complexes were characterized by particle size, Fourier transform infrared (FTIR) spectroscopy, fluorescence spectroscopy, surface hydrophobicity, contact angle, and transmission electron microscope (TEM). Results showed that the binding of LPF to EGCG was driven by hydrogen bonding and hydrophobic interaction. Both interactions play a pivotal role in the cross-linking of LPF and the transformation of the elongated fibrillar morphology of LPF into fibrillar aggregates networks, and even large-sized non-amyloid fibril aggregates, with particle size increasing from 564 nm to 3221 nm. Droplet size and confocal laser scanning microscopy (CLSM) results showed that the O/W emulsions containing 30% and 50% (w/w) oil stabilized by LPF-EGCG complex (EGCG-to-protein ratio, EGCG/P = 0.04) exhibited smallest and uniform droplet sizes (9.25 μm and 11.50 μm, respectively). The reason was that an appropriate concentration of EGCG can fine-tune the hydrophobic/hydrophilic balance and network structures of LPF, thus enhancing the stability of emulsions. Moreover, emulsions containing 30% (w/w) oil stabilized by LPF-EGCG complexes (EGCG/P > 0.02) exhibited rheological behavior similar to emulsions containing 50% oil stabilized by LPF alone, indicating potential applications in the production of fat reduced emulsion with desirable textures. These findings provide a new perspective on the structural remodeling of plant-based protein fibrils mediated by phenolic compounds, expanding their application in the production of fat-reduced emulsion-based food products. [Display omitted] • The binding of LPF to EGCG was driven by hydrophobic interaction and hydrogen bonding. • EGCG induced exposure of hydrophobic groups of LPF in a concentration-dependent manner. • EGCG remodeled LPF from fibrils aggregates into large non-amyloid fibril aggregates. • EGCG significantly improved the stability and texture of emulsions stabilized by LPF. [ABSTRACT FROM AUTHOR]

Intracranial hemorrhage (ICH) causes high mortality and disability without effective treatment in the clinical setting. (−)-Epigallocatechin-3-gallate (EGCG) exerts an essential role in the central nervous system and offers a promising therapeutic agent for the treatment of oxidative damage-related diseases. MiR-137 can inhibit the oxidative stress and apoptosis to attenuate neuronal injury. However, the role of EGCG in regulating miR-137-3p and neuronal Parthanatos remains to be unclear. In the present study, we build the ICH mice model to investigate the antioxidant effects of EGCG via upregulating miR-137-3p and inhibiting neuronal Parthanatos. We revealed that EGCG upregulated miR-137-3p and inhibited neuronal Parthanatos, and promoted the functional recovery, alleviated ICH-induced brain injury, and reduced oxidative stress in mice following ICH. However, following the inhibition of miR-137-3p and activation of Parthanatos, EGCG was unable to exert neuroprotective roles. These combined results suggest that EGCG may upregulate miR-137-3p and inhibit neuronal Parthanatos to accelerate functional recovery in mice after ICH, laying the foundation for EGCG to be a novel strategy for the treatment of neuronal injuries related to Parthanatos.

Spinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Liu and Chen.)

[Display omitted] • EGCG addition improved the solubility of myofibrillar protein (MP) in water. • Ultrasound pretreatment promoted the grafting of EGCG onto the MP. • Ultrasound combined with covalent modification of EGCG hindered myosin self-assembly. • Ultrasound combined with covalent modification of EGCG reduced MP particle size. • Introduction of EGCG enhanced the antioxidant property of MP suspensions. This study investigated the effect of (−)-Epigallocatechin-3-gallate (EGCG) non-covalent/covalent grafting onto myofibrillar protein (MP) by high-intensity ultrasound (HIU) on its water-solubility and filament forming behavior. The results showed that the introduction of EGCG, especially in the case of covalent grafting, could inhibit the molecular assembly of myosin and improve the MP water solubility from 2.7% to 53.1% (P < 0.05). The HIU pretreatment provided more opportunities for EGCG grafting onto the ultrasound-treated protein (UMP) by disrupting the filamentous polymerization of myosin and thus further facilitated MP dissolution. Additionally, compared with the UMP-EGCG non-covalent complexes, the covalent complexes with a yellow appearance exhibited a higher absolute zeta potential (35.9 mV) and a lower particle size (53.7 μm) (P < 0.05). Overall, the combination of HIU pretreatment and EGCG covalent modification may provide a promising method for improving the solubility and processing properties of MP in low ionic media (prototype soup). [ABSTRACT FROM AUTHOR]

Natural deep eutectic solvents (NADES) are considered an efficient reaction medium for the production of glycated proteins. By optimizing the Maillard reaction conditions through response surface analysis, a glycation product (GOVA) of ovalbumin (OVA) with high grafting degree (92.2%) was prepared in choline chloride/glucose NADES. The binding information of (−)-epigallocatechin-3-gallate (EGCG) to OVA/GOVA was acquired by fluorescence spectroscopy and molecular docking. The interaction strength of GOVA + EGCG was higher than that of OVA + EGCG. Hydrogen bonding and van der Waals forces were the major driving forces in the binding process. Glycation and EGCG binding reduced the surface hydrophobicity, α-helix content and digestibility of OVA. Compared with OVA, the particle sizes of GOVA and GOVA + EGCG were increased by 54.8% and 87.7%, respectively. In addition, glycation increased the emulsifying activity index and foaming capacity of OVA by 32.6% and 20.0%, respectively, which was further increased in the presence of EGCG. The encapsulation of OVA, especially GOVA, improved the antioxidant activity, stability and bioaccessibility of EGCG. The results suggest that the glycated proteins based on NADES may provide an effective alternative for the protection and transport of bioactive ingredients in the food industries. [Display omitted] • Ovalbumin (OVA) was efficiently glycated in natural deep eutectic solvents. • Glycated OVA (GOVA) had a stronger interaction with (−)-epigallocatechin-3-gallate (EGCG). • Glycation and EGCG binding reduced the surface hydrophobicity and α-helix content of OVA. • The GOVA + EGCG nanocomplex had improved functional properties. [ABSTRACT FROM AUTHOR]

The effects of nanoparticles (NPs) on microbiota homeostasis and their physiological relevance are still unclear. Herein, we compared the modulation and consequent pharmacological effects of oral administration of (−)-epigallocatechin-3-gallate (EGCG)-loaded β-cyclodextrin (β-CD) NPs (EGCG@β-CD NPs) and EGCG on gut microbiota. EGCG@β-CD NPs were prepared using self-assembly and their influence on the intestinal microbiome structure was analyzed using a metagenomics approach. The “Encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential” of EGCG@β-CD NPs were recorded as 98.27 ± 0.36%, 124.6 nm, 0.313 and –24.3 mV, respectively. Surface morphology of EGCG@β-CD NPs was observed as spherical. Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and molecular docking studies confirmed that EGCG could be well encapsulated in β-CD and formed as EGCG@β-CD NPs. After being continuously administered EGCG@β-CD NPs for 8 weeks, the serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and liver malondialdehyde (MDA) levels in the rats were significantly decreased, while the levels of catalase (CAT) and apolipoprotein-A1 (apo-A1) in the liver increased significantly in the hyperlipidemia model of rats, when compared to the high-fat-diet group. Furthermore, metagenomic analysis revealed that the ratio of Verrucomicrobia/Bacteroidetes was altered and Bacteroidetes decreased in the high-fat diet +200 mg/kg·bw EGCG@β-CD NPs group, while the abundance of Verrucomicrobia was significantly increased, especially Akkermansia muciniphila in rat feces. EGCG@β-CD NPs could be a promising EGCG delivery strategy to modulate the gut microbiota, enhancing its employment in the prevention of hyperlipidemia.

• Alkaline-treated soybean protein isolate (SPI) had better functional properties. • The affinity of treated SPI and (−)-epigallocatechin-3-gallate (EGCG) were enhanced. • Antioxidant activity and EGCG bioaccessibility were improved. Polyphenols are readily affected by environmental factors, such as heat and light, which cause them to degrade; however, the functional properties of polyphenols can be protected by complexing them with proteins. In this study, we investigate the effects of acid and alkali treatments on the functional properties of soybean protein isolate (SPI) and interactions between the treated protein and (−)-epigallocatechin-3-gallate (EGCG). The results show that alkali treatment (pH 12–7) affects the structure and functional performance of the protein more significantly than acid treatment (pH 2–7) because the protein structure unfolds, resulting in improved solubility, surface hydrophobicity, and emulsification. In addition, because alkali treatment can change the structure of a protein more than acid treatment, its structure loosens. The interactions between alkali-treated proteins and EGCG were also found to be stronger than those of acid-treated proteins and the control protein, and EGCG binds to a protein through van der Waals forces and hydrophobic interactions; these interactions protect EGCG from degradation, ensuring that its antioxidant properties are maintained and its bioavailability rate is improved. [ABSTRACT FROM AUTHOR]

Cisplatin is a widely used chemotherapeutic agent in treating various types of cancers. However, it can induce neurotoxicity and nephrotoxicity, limiting its dose and clinical use. Although previous studies indicated the direct link between cisplatin-induced central neurotoxicity and oxidative stress, the exact mechanism is not completely understood. Therefore, herein we investigated the effects of prophylactic and concurrent treatment with (−)-epigallocatechin-3-gallate (EGCG), a natural polyphenolic neuroprotective antioxidant, on cisplatin-induced brain toxicity in rats to delineate its molecular mechanism of action. We found that cisplatin initiated a cascade of genetic, biological, and histopathological changes in the brain cortex, inducing inflammatory cytokines, appearance of scattered inflammatory cells, nitro-oxidative stress, and apoptotic proteins in the cerebral cortex. However, EGCG not only protected against cisplatin-induced inflammatory burden but also ameliorated the induction of nitro-oxidative stress and apoptotic proteins triggered by cisplatin in the cerebral cortex of pre- and co-treated rats with respect to their unprotected counterparts. EGCG anti-inflammatory effect here may be attributed to the downregulation of nuclear factor kappa B (NF-κB). Additionally, this natural polyphenol significantly ameliorated cisplatin-elicited reduction in cerebral cortex brain-derived neurotrophic factor and acetylcholine esterase. Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream heme oxygenase-1 (HO-1) by EGCG prophylactic and concurrent administration here seems also to play a key role in the protective impact of EGCG against cisplatin toxicity through enhancing total antioxidant capacity. Thus, EGCG can be used as a promising prophylactic adjuvant for preventing the development of brain inflammation and oxidative damage associated with cisplatin chemotherapy. [ABSTRACT FROM AUTHOR]

Intracranial hemorrhage (ICH) causes high mortality and disability without effective treatment in the clinical setting. (−)-Epigallocatechin-3-gallate (EGCG) exerts an essential role in the central nervous system and offers a promising therapeutic agent for the treatment of oxidative damage-related diseases. MiR-137 can inhibit the oxidative stress and apoptosis to attenuate neuronal injury. However, the role of EGCG in regulating miR-137- 3p and neuronal Parthanatos remains to be unclear. In the present study, we build the ICH mice model to investigate the antioxidant effects of EGCG via upregulating miR-137-3p and inhibiting neuronal Parthanatos. We revealed that EGCG upregulated miR-137-3p and inhibited neuronal Parthanatos, and promoted the functional recovery, alleviated ICH-induced brain injury, and reduced oxidative stress in mice following ICH. However, following the inhibition of miR-137-3p and activation of Parthanatos, EGCG was unable to exert neuroprotective roles. These combined results suggest that EGCG may upregulate miR-137-3p and inhibit neuronal Parthanatos to accelerate functional recovery in mice after ICH, laying the foundation for EGCG to be a novel strategy for the treatment of neuronal injuries related to Parthanatos. [ABSTRACT FROM AUTHOR]

Background ‒ Spinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear. Methods ‒ In the present study, we established primary cerebellar granule neurons (CGNs) and a T10 ST rat model to investigate the antioxidant effects of EGCG via its modulation of protein kinase D1 (PKD1) phosphorylation and inhibition of ferroptosis. Results ‒ We revealed that EGCG significantly increased the cell survival rate of CGNs and PKD1 phosphorylation levels in comparison to the vehicle control, with a maximal effect observed at 50 µM. EGCG upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST. Conclusion ‒ Together, these results lay the foundation for EGCG as a novel strategy for the treatment of SCI related to PKD1 phosphorylation and ferroptosis. [ABSTRACT FROM AUTHOR]

A food-grade emulsion gel was stabilized using waxy maize starch (WS) incorporated (−)-epigallocatechin-3-gallate (EGCG) at different ratio (from 5 % to 20 %, w/w). The microstructure, rheological behavior, physical stability and antioxidant activity of emulsion gels were investigated using confocal laser scanning microscopy (CLSM), cryo-scanning electron microscopy (cryo-SEM), and rheometer, etc. The results suggested that incorporated EGCG obviously affected the spatial configuration of WS hydrogel. The WS/EGCG hydrogels presented an excellent lipophilic capacity characterized by tightly adhering to linseed oil droplets in the emulsion gels. Moreover, the viscosity, viscoelasticity and physical stability of the emulsion gels stabilized by the WS/EGCG hydrogel matrices were significantly enhanced. The emulsion gel stabilized by the WS/EGCG hydrogel matrix (15 % EGCG) had long-term emulsifying stability because its emulsified phase volume fraction (77.14 %) remained stable for 30 days. Compared with typical natural and synthetic antioxidants in food and pharmaceutical processing, the emulsion gels stabilized by the WS/EGCG hydrogel matrices showed significant stronger DPPH (97.45 %) and ABTS•+ (97.97 %) free radical scavenging activity. These results demonstrate that WS/EGCG hydrogels can not only be used in food-grade matrix materials to stabilize emulsion gels but also improve the antioxidant activity of the emulsion gels. [Display omitted] • Addition of EGCG has visible effect on microstructure of waxy starch hydrogel. • WS-EGCG interactions endow the starch hydrogel with lipophilicity. • WS/EGCG hydrogels can absorb on the surface of oil droplets as stabilizers. • WS/EGCG hydrogel can form an orderly network structure on emulsion droplets. [ABSTRACT FROM AUTHOR]

Ectropis obliqua Prout is the main pest of the tea plant Camellia sinensis (L.) O. Kuntze in China, affecting an annual area of more than one million acres. (−)-Epigallocatechin-3-gallate (EGCG) is the major catechin in tea leaves. Here, we show that EGCG is highly efficient in increasing the survival rate of E. obliqua larvae. We also compared the gut peroxidase (PO) activity between EGCG-fed and control larvae. EGCG-fed larvae had significantly greater PO activity levels than control larvae. Western blotting validated these results. Gut PO activity levels of larvae fed an artificial diet gradually decreased and disappeared completely by day 5. We hypothesize that the increased survival rate of EGCG-fed larvae was associated with increased PO activity. This research provides evidence that E. obliqua larvae have adapted to, and may even benefit from, secondary compounds found in tea leaves. [ABSTRACT FROM AUTHOR]

Abstract β-lactoglobulin (β-lg), the predominant protein in bovine whey, was chemically modified by (−)-epigallocatechin-3-gallate (EGCG) to develop a biomacromolecule with antioxidant activity. The EGCG-modified β-lg was characterized by SDS-PAGE, MALDI-TOF MS and intrinsic fluorescence spectroscopy. The antioxidant properties of EGCG-modified β-lg was assessed using DPPH radical scavenging activity, iron chelating ability, and inhibition of Cu2+-induced LDL oxidation. SDS-PAGE and MALDI-TOF MS results indicated the dimerization of β-lg after EGCG modification. Intrinsic fluorescence spectra suggested that EGCG modification caused an alteration in the conformational structure of β-lg. The results demonstrated that EGCG-modified β-lg possessed great antioxidant potential in terms of scavenging DPPH radical and chelating ferrous ion. Furthermore, the EGCG-modified β-lg showed a protective effect against LDL peroxidation. The results indicate that EGCG-modified β-lg could provide significant health benefits as an antioxidant. Highlights • Covalent modification by EGCG caused the formation of β-lg dimer. • EGCG modification altered β-lg conformation making it more hydrophilic. • EGCG-modified β-lg is a novel biomacromolecule with antioxidant activity. [ABSTRACT FROM AUTHOR]

(−)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea, is a potential anticancer agent, but the molecular mechanisms of its effects are not well-understood. The present study was conducted to examine the mechanism of EGCG in lung cancer cells. Alterations in long non-coding RNAs (lncRNAs) and mRNAs were investigated in lung cancer cells treated with EGCG by lncRNA microarray analysis. Furthermore, the functions and signaling pathways regulated by EGCG were predicted by bioinformatics analysis. A total of 960 lncRNAs and 1,434 mRNAs were significantly altered following EGCG treatment. These lncRNAs were distributed across nearly all human chromosomes and the mRNAs were involved in the cell cycle and the mitotic cell cycle process. Through a combination of microarray and bioinformatics analysis, 20 mRNAs predicted to serve a key role in the EGCG regulation were identified, and certain regulatory networks involving EGCG-regulated lncRNAs were predicted. In conclusion, EGCG affects the expression of various lncRNAs and mRNAs in the cells, therefore affecting cell functions. The results of the present study provide an insight into the mechanism of EGCG, which may be useful for therapeutic development. [ABSTRACT FROM AUTHOR]

Highlights • pH-shifting treatment induced the structural changes of whey protein isolate (WPI). • The structural changes resulted improved functional properties. • Enhanced interaction of treated WPI and (-)-epigallocatechin-3-gallate (EGCG). • Better protection of EGCG and its antioxidant activity in treated WPI. Abstract Effect of pH-shifting on structural and functional properties of whey protein isolate and its interaction with (−)-epigallocatechin-3-gallate were investigated. Circular dichroism spectra showed that pH-shifting induced the decrease in α-helix content by 12.18% and β-sheet content by 3.24%, but β-turn and random coil content increased by 4.26% and 5.91%, respectively. Increase of fluorescence intensity and red-shift of maximum emission wavelength indicated the structural unfolding and exposure of tyrosine. The treatment also significantly increased the surface hydrophobicity, disulfide bonds content, solubility, emulsifying activity and emulsion stability of whey protein isolate at P < 0.05 level. Fluorescence quenching analysis revealed that treated whey protein isolate have a stronger binding affinity to (−)-epigallocatechin-3-gallate, resulting a better protection against the degradation of (−)-epigallocatechin-3-gallate and its antioxidant activity. This study confirmed that pH-shifting treatment can improve functional properties of whey protein isolate and its potential as a protective carrier for polyphones. [ABSTRACT FROM AUTHOR]

BACKGROUND: Soy protein isolate (SPI) has promising applications in various food products because of its excellent functional properties and nutritional quality. The structural and emulsifying properties of covalently modified SPI by (−)‐epigallocatechin‐3‐gallate (EGCG) were investigated. RESULTS: SPI was covalently modified by EGCG under alkaline conditions. SDS‐PAGE analysis revealed that EGCG modification caused crosslinking of SPI proteins. Circular dichroism spectra demonstrated that the secondary structure of SPI proteins was changed by EGCG modification. In addition, the modifications resulted in the perturbation of the tertiary structure of SPI as evidenced by intrinsic fluorescence spectra and surface hydrophobicity measurements. Oil‐in‐water emulsions of modified SPI had smaller droplet sizes and better creaming stability compared to those from unmodified SPI. CONCLUSION: The covalent modification by EGCG improved the emulsifying property of SPI. This study therefore provided an innovative approach for improving the emulsifying properties of proteins. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

It has been acknowledged that environmental stress is a risk factor for developing mental disorders. Chronic stress may contribute to the hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and a sustained rise in the levels of glucocorticoids (GCs). A high concentration of corticosterone (CORT) damages neuronal PC12 cells. It has been reported that (−)-Epigallocatechin-3-gallate (EGCG), a major component of green tea, exhibits neuroprotective activity. However, the protective effect of EGCG on neuronal cells injured by CORT remains to be elucidated. The present study aimed to identify the effects of EGCG on CORT-injured neuronal PC12 cells and its associated mechanisms of action. CORT-injured PC12 cells were pretreated with EGCG with or without cyclopamine. Cell viability was assessed using an MTT assay, changes in cell morphology were observed using phase-contrast microscopy, cellular apoptosis was assessed by Hoechst 33342 staining, cell proliferation was measured using a cell counting kit-8 assay, mRNA levels were measured by reverse transcription-quantitative polymerase chain reaction and protein expression was assessed using western blot analysis. The current study demonstrated that exposure to high concentrations of CORT induced cytotoxicity and downregulated the Sonic hedgehog pathway (Shh) in PC12 cells. These effects were attenuated by EGCG. However, the EGCG-mediated neuroprotective effects, as well as upregulation of the Shh pathway were all attenuated by the Shh signaling inhibitor cyclopamine. These results indicate that EGCG protects PC12 cells from CORT-induced neurotoxicity via activation of the Shh signaling pathway. [ABSTRACT FROM AUTHOR]

The dose-dependent effects of (−)-epigallocatechin-3-gallate (EGCG; at 0, 50, 100, 200, 500, and 1000 mg/L) on the physical, chemical, and oxidative stability of porcine myofibrillar protein (MP)–soybean oil emulsion systems were investigated. The results showed EGCG at all levels effectively suppressed lipid oxidation in MP emulsion composite gels during the entire chill storage (at 4 °C for 0, 3, or 7 days). The incorporation of EGCG at higher concentrations (>100 mg/L) promoted the loss of sulfhydryls, reduction of surface hydrophobicity, and aggregation and cross-linking of MP. As a result, high concentrations of EGCG (500 and 1000 mg/L) hampered emulsification and gel formation of MP. However, EGCG at lower concentrations (50–200 mg/L) improved the oxidative stability of meat emulsions without jeopardizing the textural stability. [ABSTRACT FROM AUTHOR]

(‑)‑Epigallocatechin‑3‑gallate (EGCG) is the most widely studied catechin in green tea and has been identified to regulate immune function. The objective of the present study was to explore the possible application of EGCG in the treatment of Parkinson's disease (PD) by examining its effects on the peripheral immune system in the 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP)‑induced PD mouse model. The results demonstrated that EGCG treatment restored the movement behavior of the mice impaired by MPTP, and protected tyrosine hydroxylase‑positive cells in the substantia nigra pars compacta region from MPTP toxicity. Flow cytometric analysis indicated that the ratio of CD3+CD4+ to CD3+CD8+ T lymphocytes in the peripheral blood increased in MPTP‑treated mice following treatment with EGCG, and EGCG reduced expression of inflammatory factors tumor necrosis factor‑α and interleukin‑6 in serum. The present findings indicated that EGCG serves neuroprotective effects in an MPTP‑induced PD mice model and may exert this through modulating peripheral immune response. [ABSTRACT FROM AUTHOR]

(-)-Epigallocatechin-3-gallate (EGCG) is a polyphenol monomer compound extracted and separated from green tea, and is a key catechin in green tea. Recent research has identified that EGCG is equipped with important biological activities, including antitumor, antioxidant, anti-inflammation, blood fat reduction and radiation protection abilities. In the current study, it was investigated whether EGCG exerts a neuroprotective effect on AIT and examined the possible underlying mechanism. The present study sought to establish an experimental autoimmune thyroiditis (AIT) rat model and to investigate the neuroprotective effect of EGCG in this model. EGCG was demonstrated to inhibit urinary iodine values and thyroid pathological features in AIT model rats. Treatment with EGCG significantly reduced interleukin-1β, interferon-γ (INF-γ) and tumor necrosis factor-α (TNF-α) levels in the AIT rats through suppression of nuclear factor-κB (NF-κB) pathway. In addition, pretreatment with EGCG significantly increased B-cell lymphoma-2 protein expression, and suppressed caspase-3 activity and TNF-α-related apoptosis-inducing ligand (TRAIL) protein expression levels in the AIT model rats. In conclusion, these results suggested that the neuroprotective effect of EGCG protects against AIT through its anti-inflammatory ability, anti-apoptosis and TRAIL signaling pathway in model rats, and it may be used as a therapeutic agent against AIT caused by inflammation. [ABSTRACT FROM AUTHOR]

The current study was designed to examine the role of galloyl moieties in the interaction of β -lactoglobulin ( β -Lg) with (−)-epigallocatechin-3-gallate (EGCG) using fluorescence and CD spectroscopic methods. The interactions with β -Lg were investigated for EGCG, (−)-epigallocatechin (EGC), and the phenolic compound methyl gallate (MeG) at pH values 3.0, 5.0 and 7.4. The spectroscopic data indicated the binding constants for polyphenol complexes with β -Lg in phosphate buffer pH 7.4 to be in the order of MeG > EGCG > EGC. MeG exhibited the strongest quenching efficiency compared to EGCG and EGC, and EGC exhibited the weakest quenching efficiency. The quenching efficiency of EGCG on β -Lg fluorescence decreased with increasing pH. Polyphenols binding results in a slight secondary structural change of β -Lg, consistent with the fluorescence analysis. This study confirmed that the high binding affinity of EGCG to β -Lg is due to the galloyl functional group. [ABSTRACT FROM AUTHOR]

[Display omitted] • SPI–EGCG–maltose ternary conjugate was prepared via ultrasound and the Maillard reaction. • The ternary conjugate showed superior solubility, emulsification and foaming and antioxidant activity properties. • β-Carotene nanoemulsion was prepared with the SPI–EGCG–maltose ternary conjugate as the emulsifiers via ultrasound. • The nanoemulsion can effectively prevent the oxidation and degradation of β-carotene. In this study, a ternary conjugate was prepared by covalent bonding of protein, polysaccharide, and polyphenol via ultrasound and the Maillard reaction. Subsequently, the β-carotene nanoemulsion was prepared with the soy protein isolate–(−)-epigallocatechin gallate–maltose (SPI–EGCG–maltose) conjugate as the emulsifiers via ultrasound. The SPI–EGCG–maltose conjugate showed superior solubility, emulsification and foaming properties at 4 h reaction time. Meanwhile, the retention rates of β-carotene in the nanoemulsion after 30 d of storage, 8 h of light, and 55 °C of heat were >60%, >75%, and >60%, respectively. Furthermore, ultrasound treatment at 500 W for 10 min produced an inhibitory effect on the degradation of β-carotene. This study indicates that the nanoemulsion based on the ternary conjugate can effectively inhibit the β-carotene degradation by the external environment and prevent the oxidation and degradation of β-carotene in the nanoemulsion. [ABSTRACT FROM AUTHOR]

The effect of (−)-epigallocatechin-3-gallate (EGCG) on protein structure and emulsion properties of glycosylated black bean protein isolate (BBPI-G) were studied and compared to native black bean protein isolate (BBPI). The binding affinity of BBPI and BBPI-G with EGCG belonged to non-covalent interaction, which was determined by fluorescence quenching. EGCG attachment caused more disordered protein conformation, leading to a higher emulsification property. Among the different EGCG concentrations (0.10, 0.25, 0.50 mg/mL), the result revealed that the highest level of the emulsification property was obtained with 0.25 mg/mL EGCG. Therefore, the BBPI-EGCG and BBPI-G-EGCG prepared by 0.25 mg/mL EGCG were selected to fabricate oil-in-water (O/W) emulsions. After the addition of EGCG, the mean particle size of emulsions decreased with the increasing absolute value of zeta-potential, and more compact interfacial film was formed due to the higher percentage of interfacial protein adsorption (AP%). Meanwhile, EGCG also significantly reduced the lipid oxidation of emulsions.

Purpose: In this study, we examined the effects of epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on sepsis-induced neurocognitive abnormity in aged rats. Methods: Aged rats received an intraperitoneal (i.p.) injection of 5.0 mg/kg lipopolysaccharide (LPS) or saline. Animals were further divided into three groups: control, low-dose EGCG (4.0 mg/kg), and high-dose EGCG (20 mg/kg). EGCG was i.p. injected at the same time, 24 and 48 h after LPS administration. Survival rate was recorded for 1 week. All surviving animals were assessed for cognitive function using the novel object recognition test, followed by measurement of hippocampal cytokine levels. In an additional set of experiments, the liver function test was performed. Furthermore, the effects of EGCG on cytokine release from microglia isolated from young and aged rats were assessed. Results: The survival rate in LPS-treated control rats was 77.8%, which was decreased to 72.2 and 33.3% in the low and high EGCG groups, respectively. In the surviving animals, the LPS-treated control rats exhibited impaired cognitive performance and increased pro-inflammatory cytokine levels compared with untreated animals. None of these neurocognitive alterations were affected by low or high EGCG treatment. Blood chemical analysis showed co-administration of EGCG with LPS resulted in a marked increase in both aspartate aminotransferase and alanine aminotransferase levels. In addition, EGCG inhibited LPS-induced cytokine release, whereas the suppressive ability of EGCG was lower in aged microglia compared with in young microglia. Conclusions: Our findings demonstrated that EGCG cannot prevent hippocampal neuroinflammation and related memory deficits in aged rats surviving sepsis. [ABSTRACT FROM AUTHOR]

We investigated the molecular mechanisms involved in the angiotensin-converting enzyme (ACE) inhibition by (−)-epigallocatechin-3-gallate (EGCg), a major tea catechin. EGCg inhibited both the ACE activity in the lysate of human colorectal cancer cells and human recombinant ACE (rh-ACE) in a dose-dependent manner. Co-incubation with zinc sulfate showed no influence on the rh-ACE inhibition by EGCg, whereas it completely counteracted the inhibitory effect of ethylenediaminetetraacetic acid, a chelating-type ACE inhibitor. Although hydrogen peroxide was produced by the autoxidation of EGCg, hydrogen peroxide itself had little effect on the ACE activity. Conversely, the co-incubation of EGCg with borate or ascorbic acid significantly diminished the EGCg inhibition. A redox-cycling staining experiment revealed that rh-ACE was covalently modified by EGCg. A Lineweaver-Burk plot analysis indicated that EGCg inhibited the ACE activity in a non-competitive manner. These results suggested that EGCg might allosterically inhibit the ACE activity through oxidative conversion into an electrophilic quinone. [ABSTRACT FROM AUTHOR]

Aims (−)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol compound, plays an important role in the prevention of cardiovascular disease and cancer. The present study aimed to investigate the effects of EGCG on doxorubicin (DOX)-induced cardiotoxicity in Sarcoma 180 (S180) tumor-bearing mice. Main methods S180 tumor-bearing mice were established by subcutaneous inoculation of S180 cells attached to the axillary region. The extent of myocardial injury was accessed by the amount of lactate dehydrogenase (LDH) released in serum. Heart tissue was morphologically studied with transmission electron microscopy. Apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (ΔѰm) as well as calcium concentration were measured by flow cytometric analysis. Expression levels of manganese superoxide dismutase (MnSOD) were analyzed by Western blot. Key findings Results showed that the combination with EGCG and DOX significantly inhibited tumor growth and enhanced induction of apoptosis compared with DOX alone. Moreover, administration of EGCG could suppress DOX-induced cardiotoxicity as evidenced by alleviating LDH release and apoptosis in cardiomyocyte. EGCG-evoked cardioprotection was in association with the increase of ΔѰm and MnSOD expression. EGCG was also found to attenuate ROS generation and myocardial calcium overload in Sarcoma 180 tumor-bearing mice subjected to DOX. Significance EGCG alleviated DOX-induced cardiotoxicity possibly in part mediated by increasing of MnSOD and Ѱm, reducing myocardial calcium overload and subsequently attenuating the apoptosis and LDH release. Our findings suggest that co-administration of EGCG and DOX have potential as a feasible strategy to mitigate cardiotoxicity of DOX without compromising its chemotherapeutic value. [ABSTRACT FROM AUTHOR]

(−)-Epigallocatechin-3-gallate (EGCG), the predominant constituent of green tea, has been demonstrated to be neuroprotective against acute ischemic stroke. However, the long-term actions of EGCG on neurogenesis and functional recovery after ischemic stroke have not been identified. In this study, C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion for 28 days. Neural progenitor cells (NPCs) were isolated from ipsilateral subventricular zone (SVZ) at 14 days post-ischemia (dpi). The effects of EGCG on the proliferation and differentiation of NPCs were examined in vivo and in vitro. Behavioral assessments were made 3 days before MCAO and at 28 dpi. SVZ NPCs were stimulated with lipopolysaccharide (LPS) in vitro to mimic the inflammatory response after ischemic stroke. We found that 14 days treatment with EGCG significantly increased the proliferation of SVZ NPCs and the migration of SVZ neuroblasts, as well as functional recovery, perhaps through M2 phenotype induction in microglia. LPS stimulation promoted the neuronal differentiation in cultured NPCs from the ischemic SVZ. EGCG treatment (20 or 40 μM) further significantly increased the neuronal differentiation of LPS-stimulated SVZ NPCs. After screening for multiple signaling pathways, the AKT signaling pathway was found to be involved in EGCG-mediated proliferation and neuronal differentiation of NPCs in vitro. Taken together, our results reveal a previously uncharacterized role of EGCG in the augment of proliferation and neuronal differentiation of SVZ NPCs and subsequent spontaneous recovery after ischemic stroke. Thus, the beneficial effects of EGCG on neurogenesis and stroke recovery should be considered in developing therapeutic approaches. [ABSTRACT FROM AUTHOR]

Fibrillogenesis of amyloid β-protein (Aβ) in human brain has been implicated as the main cause of Alzheimer’s disease. A few small molecules from natural sources have been discovered for their inhibition effects on Aβ fibrillation, of which (−)-epigallocatechin-3-gallate (EGCG) is one of the most broadly investigated compounds for its potent inhibitory activity. However, in vivo applicability of the inhibitors is largely limited by their low transmembrane efficiency. Hence, it is of great significance to develop inhibition systems that function at low concentrations. In this work, a dual-inhibitor system containing EGCG and negatively charged polymeric nanoparticles (NP10), which was also demonstrated effective on the inhibition of Aβ aggregation, was developed and comprehensively studied by extensive biophysical and biological assays. It was found that the dual-inhibitor system at low concentrations was more effective on the inhibition and detoxification of Aβ (Aβ 42 and Aβ 40 ) fibrillation than the additive effects of these two agents working individually. Namely, there was a synergistic effect of the two inhibitors. The synergism factor reached 1.25 with 5 μM EGCG and 5 μg/mL NP10. Kinetic studies with Aβ 40 revealed that the two inhibitors functioned in different Aβ assembling stages: NP10 mainly inhibited primary nucleation, while EGCG suppressed fibril elongation and changed the fibril structure to make it show less seeding activities in the secondary nucleation. NP10 might also help EGCG binding to Aβ, leading to its enhanced inhibitory effects on fibril elongation and secondary nucleation. The synergistic effect observed in the dual-inhibitor system offered new insight into the development of potent inhibitor systems against amyloid neurotoxicity. [ABSTRACT FROM AUTHOR]

Heat shock proteins (Hsps), amongst them, Hsp70 and Hsp90 families, serve mainly as facilitators of protein folding (molecular chaperones) of the cell. The Hsp70 family of proteins represents one of the most important molecular chaperones in the cell. Plasmodium falciparum, the main agent of malaria, expresses six Hsp70 isoforms. Two (PfHsp70-1 and PfHsp70-z) of these localize to the parasite cytosol. PHsp70-1 is known to occur in a functional complex with another chaperone, PfHsp90 via a co-chaperone, P. falciparum Hsp70-Hsp90 organising protein (PfHop). (−)-Epigallocatechin-3-gallate (EGCG) is a green tea constituent that is thought to possess antiplasmodial activity. However, the mechanism by which EGCG exhibits antiplasmodial activity is not fully understood. A previous study proposed that EGCG binds to the N-terminal ATPase domain of Hsp70. In the current study, we overexpressed and purified recombinant forms of two P. falciparum cytosol localized Hsp70s (PfHsp70-1 and PfHsp70-z), and PfHop, a co-chaperone of PfHsp70-1. Using the surface plasmon resonance approach, we demonstrated that EGCG directly binds to the two Hsp70s. We further observed that binding of EGCG to the two proteins resulted in secondary and tertiary conformational changes. In addition, EGCG inhibited the ATPase and chaperone function of the two proteins. Furthermore, EGCG abrogated association of the two Hsp70s with their functional partners. Using parasites cultured in vitro at the blood stages, we observed that 2.9 µM EGCG suppressed 50% P. falciparum parasite growth (IC50). Our findings demonstrate that EGCG directly binds to PfHsp70-1 and PfHsp70-z to inhibit both the ATPase and chaperone functions of the proteins. Our study constitutes the first direct evidence suggesting that the antiplasmodial activity of EGCG is at least in part accounted for by its inhibition of Hsp70 function.

• Both EGCG conjugation and conjugation method affect the structure of WPI. • The highest grafting efficiency was obtained by tyrosinase-catalyzed oxidation. • The conjugates showed better emulsifying and antioxidant activity. • The antioxidant activities of conjugates are proportional to their EGCG content. • β-Carotene stability was positively correlated with EGCG content in conjugates. (−)-Epigallocatechin-3-gallate (EGCG) was conjugated to whey protein isolate (WPI) using alkaline treatment, free radical grafting and tyrosinase-catalyzed oxidation. The structure and properties of the obtained conjugates and their application as antioxidant emulsifiers in stabilizing β-carotene emulsion were systematically characterized. Fourier transform infrared spectroscopy and sodium dodecyl sulfate–polyacrylamide gel electrophoresis verified the covalent linking between WPI and EGCG. The highest grafting efficiency was obtained for enzyme conjugate, followed for alkaline conjugate. Conjugation of EGCG decreased the α-helix content and fluorescence intensity of protein, and these changes depend on both EGCG conjugation and the cross-linking methods. Due to their improved emulsifying properties and antioxidant activity, WPI-EGCG conjugates formed smaller emulsion droplets and protect the encapsulated β-carotene more effectively, and the protective property is positively correlated with EGCG content in conjugates. [ABSTRACT FROM AUTHOR]

Scope: Existing research suggests that (-)-epigallocatechin-3-gallate (EGCG), which is a natural tea catechin active substance, can protect against liver injury. However, its mechanism for hepatic encephalopathy (HE) treatment is still unclear. In this study, the role of EGCG in the amelioration of HE rats and the effect on the microbiota-gut-liver axis are mainly analyzed., Methods and Results: Thioacetamide (TAA) is employed to induce the HE model in rats. The results of open field test show that EGCG restores locomotor activity and exploratory behavior. Histological and biochemical results demonstrate that EGCG ameliorates brain and liver damage, decreases the expression of pro-inflammatory cytokines, and increases the activity of antioxidant enzymes. Meanwhile, EGCG modulates the Nrf2 pathway and TLR4/NF-κB pathway to mitigate TAA-induced oxidative stress and inflammatory responses. Immunohistochemistry reveals protection of the intestinal barrier by EGCG upregulating the expression of occludin and zonula occludens-1. Furthermore, serum levels of ammonia and LPS are reduced. 16S rRNA analysis shows that EGCG treatment increases the abundance of beneficial bacteria (e.g., Bifidobacterium, Lactobacillus, and Limosilactobacillus)., Conclusion: The above results reveal that EGCG has anti-oxidative stress and anti-inflammatory effects, and ameliorates the condition through the microbiota-gut-liver axis, with potential for the treatment of HE., (© 2023 Wiley-VCH GmbH.)

(−)-Epigallocatechin-3-gallate (EGCG), the main active ingredient from the green tea leaves ( Camelia sinensis L.), is a hydrophilic drug with low-oral bioavailability (BCS class III). A novel self-double-emulsifying drug delivery system (SDEDDS) in solid form was formulated to improve the oral absorption of EGCG. Solubility of EGCG was determined in various components including water, oils, and surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The EGCG-SDEDDS in solid formulation rapidly formed fine water-in-oil-in-water emulsion. Furthermore, in vitro cellular experiments have shown increase in the cellular uptake of EGCG incorporated in SDEDDS compared to pure drug, and in an in vivo pharmacokinetic study in rats, the SDEDDS formulation exhibited 1.93-fold greater area-under-curve value than that of the drug solution. Stability studies have shown that solid EGCG-SDEDDS was stable up to 6 months under intermediate condition. These studies demonstrated that the novel SDEDDS in solid form could be a promising formulation strategy for the drug delivery of hydrophilic compounds with low-oral bioavailability. Practical applications: Solid SDEDDS could be used as a drug delivery system to encapsulate hydrophilic drug with low-oral bioavailability. In vitro and in vivo experiments have shown increase uptake of EGCG incorporated in solid SDEDDS compared to pure drug. Solid SDEDDS also improved the storage stability of EGCG. Furthermore, the production procedure of SDEDDS is two-step method, which is widespread and easy to handle. In regard to industrial production aspects, solid SDEDDS have the chance to be exploited as drug delivery system in commercial products. Hence, solid SDEDDS could be applicable delivery system for hydrophilic compounds with low-oral bioavailability. A novel self-double-emulsifying drug delivery system (SDEDDS) in solid form is prepared by the modified two-step method. The system can spontaneously emulsify into w/o/w double emulsions in the aqueous media. Pharmacokinetic studies reveal that solid SDEDDS shows 1.93-fold absorption of EGCG compared to EGCG solution. [ABSTRACT FROM AUTHOR]

Because of the aggregation and/or gelation of lactoferrin (LF) occurred during thermal treatment, its application is limited in food products. The present study was focused on the effect of covalently binding polyphenols on the heat-induced structural changes of LF in a neutral aqueous solution. LF, LF-chlorogenic acid (CA) and LF-epigallocatechin-3-gallate (EGCG) mixtures and conjugates in sodium phosphate buffer were heated between 50 °C and 90 °C for 20 min with or without NaCl (100–200 mM). The mechanism for the inhibition of LF aggregation during thermal treatment was elucidated by multispectral and physicochemical methods. Fourier transform infrared and circular dichroism spectroscopies suggested that a higher degree of changes in the secondary structure occurred for LF than LF-polyphenol conjugates. According to physicochemical analysis, the conjugation of polyphenols to LF increased the magnitude of ζ-potential and reduced the surface hydrophobicity, resulting in a lower turbidity during heat treatment. In addition, after heating at 90 °C for 20 min, a greater extent of aggregation was found in LF than LF-polyphenol conjugates by atomic force microscope. These results revealed that LF could generate aggregates at neutral pH after heating and the conjugation of polyphenols prevented LF from thermal aggregation by steric hindrance and electrostatic repulsion. [ABSTRACT FROM AUTHOR]

Intimal macrophages are determinant cells for atherosclerotic lesion formation by releasing inflammatory factors and taking up oxidized low-density lipoprotein (oxLDL) via scavenger receptors, primarily the CD36 receptor. (-)-Epigallocatechin-3-gallate (EGCG) has a potential to decrease cholesterol accumulation and inflammatory responses in macrophages. We made EGCG-loaded nanoparticles (Enano) using phosphatidylcholine, kolliphor HS15, alpha-tocopherol acetate and EGCG. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), a CD36-targeted ligand found on oxLDL, was incorporated on the surface of Enano to make ligand-Enano (L-Enano). The objectives of this study are to deliver EGCG to macrophages via CD36-targeted L-Enano and to determine its antiatherogenic bioactivities. The optimized nanoparticles obtained in our study were spherical and around 108 nm in diameter, and had about 10% of EGCG loading capacity and 96% of EGCG encapsulation efficiency. Compared to Enano, CD36-targeted L-Enano had significantly higher binding affinity to and uptake by macrophages at the same pattern as oxLDL. CD36-targeted L-Enano dramatically improved EGCG stability, increased macrophage EGCG content, delivered EGCG to macrophage cytosol and avoided lysosomes. L-Enano significantly decreased macrophage mRNA levels and protein secretion of monocyte chemoattractant protein 1, but did not significantly change macrophage cholesterol content. The innovative CD36-targeted nanoparticles may facilitate targeted delivery of diagnostic, preventive and therapeutic compounds to intimal macrophages for the diagnosis, prevention and treatment of atherosclerosis with enhanced efficacy and decreased side effects. [ABSTRACT FROM AUTHOR]

The physicochemical and functional properties of covalently modified whey protein isolate (WPI) by (−)-epigallocatechin-3-gallate (EGCG) were investigated. WPI was chemically modified by EGCG under alkaline conditions. The effect of modification on foaming and emulsifying properties was evaluated. The results of SDS-PAGE and size exclusion chromatography indicated that modification by EGCG induced cross-linking on proteins of WPI. Fourier transform infrared spectroscopy (FT-IR) analysis illustrated the incorporation of phenolic groups into the modified WPI and the changes in protein secondary structure. Intrinsic fluorescence spectra revealed that modified WPI had a more compact tertiary structure compared to unmodified WPI. The modified WPI exhibited better foaming and emulsifying properties than unmodified WPI. These results suggest that EGCG modification is a potential method for improving the functional properties of WPI. [ABSTRACT FROM AUTHOR]

The interactions between the flavan-3-ol (−)-epigallocatechin-3-gallate ( EGCG) and bovine β-casein in phosphate-buffered saline ( PBS) of pH 6.5 subjected to thermal processing at various temperatures (25-100 °C) were investigated using fluorescence quenching. The results indicated that different temperatures had different effects on the structural changes and EGCG-binding ability of β-casein. At temperatures below 60 °C, the β-casein- EGCG interaction changed little ( P > 0.05) with increasing temperature. At temperatures above 80 °C, native assemblies of β-casein in solution dissociated into individual β-casein molecules and unfolded, as demonstrated by a red shift of the maximum fluorescence emission wavelength (λmax) of up to 8.8 nm. The highest quenching constant ( Kq) and the number of binding sites ( n) were 0.92 (±0.01) × 1013 m−1 s−1 and 0.73 (±0.02) (100 °C), respectively. These results provide insight into the potential of interactions between β-casein- EGCG that may modulate bioactivity or bioavailability to be altered during thermal process. [ABSTRACT FROM AUTHOR]