Epigallocatechin Gallate Research Articles

Electronic States of Epigallocatechin-3-Gallate in Water and in 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (Sodium Salt) Liposomes

In this work, the spectroscopy of epigallocatechin-3-gallate (EGCG) and EGCG bonded to 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (sodium salt) (DPPG) lipid is studied both experimentally by combining high-resolution vacuum ultraviolet (VUV) photo-absorption measurements in the 4.0–9.0 eV energy range and by theoretical calculations using density functional theory (DFT) methodology. There is a good agreement between the experimental and theoretical data, and the inclusion of the solvent both implicitly and explicitly further improves this agreement. For all experimentally measured absorption bands observed in the VUV spectra of EGCG in water, assignments to the calculated electronic transitions are provided. The calculations reveal that the spectrum of DPPG-EGCG has an intense peak around 150 nm, which is in accordance with experimental data, and it is assigned to an electron transfer transition from resorcinol–pyrogallol groups to different smaller groups of the EGCG molecule. Finally, the increase in absorbance observed experimentally in the DPPG-EGCG spectrum can be associated with the interaction between the molecules.

Effects of Lead Acetate Toxicity in Respect to Histological, Cytogenetical, Haematological Parameters and Subsequent Amelioration by Green Tea on Experimental Albino Rats

Lead acetate is arguably one of the environmental pollutants that threats the lives of living beings in multiple ways. Lead acetate occurs both naturally & due to human activities. Lead Acetate, a potential carcinogen, can enter the body through inhalation, ingestion, or dermal contact. Green tea and polyphenol have recently drawn attention of cell biologists. Multiple studies have confirmed the anti-inflammatory, anti-oxidative & anti-diabetic activities of polyphenols. In the Green tea extracts, Catechins including EGC (Epigallocatechin), ECG (Epicatechin-3-gallate), EGCG (Epigallocatechin-3-gallate) and EC (Epicatechin) are the major polyphenols which show a vast range of ameliorating effects on deleterious effects of different organs. Proper supplementation or dosage of green tea extracts may improve TAC (Total antioxidant capacity) and reduce the concentration of MDC (Malondialdehyde) in liver, brain and blood of vertebrates. Epicatechin supplementation could significantly lower the MDA levels and increase the glutathione concentration & catalase. It also increases superoxide dismutase (SODs, helpful antioxidant to defense against oxidative stress) & glutathione peroxidase activities in major organs. Though, high doses might have adverse effects, it has the capability to protect against oxidative damage & promote overall health. Twenty mature albino rats were used, divided into four groups of five rats per group. Group 1 (control male) were not administered with lead acetate or green tea extract; it received water only. Group 2 (male) was given lead acetate solution 0.003 ml/g; Group 3 (female) was administered with lead acetate 0.003 ml/g and Group 4 (male) was treated with lead acetate (0.003 ml/g) followed by green tea extract (0.0002 ml/g) daily. This study investigated the effect of lead acetate intoxication and ameliorating upshot of green tea extract on some haematological, histological, cytogenetical factors of Albino Rats.

Carbon quantum dots amplify beneficial effects of EGCG against neural injuries by NLRP3 inflammasome after intracerebral hemorrhage.

Neuroinflammation plays an indispensable role in neural damages after ICH, responsible for the induced high mortality and poor prognosis. NLRP3 inflammasome, which is known mediated by ROS, has been widely documented to aggravate brain injuries. Therefore, suppressing neural injuries by ROS/NLRP3 pathway may be beneficial in treating ICH. As the major catechin found in green tea, epigallocatechin-3-gallate (EGCG) shows excellent anti-oxidative and anti-inflammatory effects. In this study, EGCG-carbon quantum dots (EGCG-CQDs) were successfully fabricated based on EGCG by hydrothermal synthesis method. EGCG-CQDs exhibited an excellent aqueous solubility, and emerged more abundant phenolic oxygens as well as oxygen-rich functional groups. Importantly, EGCG-CQDs showed superior free radical scavenging activity by DPPH and ABTS assays in vitro than EGCG. In vivo, a significant antioxidative activity was presented by EGCG-CQDs rather than EGCG. Furthermore, the upregulated NLRP3 and the induced inflammatory cascades (NF-κB, Caspase-1 and GSDMD) in ICH were attenuated by EGCG-CQDs. Inflammatory factor productions were also decreased by EGCG-CQDs, such as IL-1β, IL-18, IL-6 and TNF-α. Finally, the disturbed neural viability, disordered cytomorphology, and neurological deficits were significantly improved by EGCG-CQDs rather than EGCG. Therefore, CQDs might be an effective form to amplify the efficacy and bioavailability of EGCG, exerting considerable effects on treating ICH by suppressing ROS/NLRP3.

Intervention of a Communication Between PI3K/Akt and β-Catenin by (-)-Epigallocatechin-3-Gallate Suppresses TGF-β1-Promoted Epithelial-Mesenchymal Transition and Invasive Phenotype of NSCLC Cells.

The epithelial-mesenchymal transition (EMT) assists in the acquisition of invasiveness, relapse, and resistance in non-small cell lung cancer (NSCLC) and can be caused by the signaling of transforming growth factor-β1 (TGF-β1) through Smad-mediated or Smad-independent pathways. (-)-Epigallocatechin-3-gallate (EGCG), a multifunctional cancer-preventing bioconstituent found in tea polyphenols, has been shown to repress TGF-β1-triggered EMT in the human NSCLC A549 cell line by inhibiting the activation of Smad2 and Erk1/2 or reducing the acetylation of Smad2 and Smad3. However, its impact on the Smad-independent pathway remains unclear. Here, we found that EGCG, similar to LY294002 (a specific inhibitor of phosphatidylinositol 3-kinase [PI3K]), downregulated Akt activation and restored the action of glycogen synthase kinase-3β (GSK-3β), accompanied by TGF-β1-caused changes in hallmarks of EMT such as N-cadherin, E-cadherin, vimentin, and Snail in A549 cells. EGCG inhibited β-catenin expression and its nuclear localization caused by TGF-β1, suggesting that EGCG blocks the crosstalk between the PI3K/Akt/GSK-3β route and β-catenin. Furthermore, it was shown that EGCG suppressed TGF-β1-elicited invasive phenotypes of A549 cells, including invading and migrating activities, matrix metalloproteinase-2 (MMP-2) secretion, cell adhesion, and wound healing. In summary, we suggest that EGCG inhibits the induction of EMT by TGF-β1 in NSCLC not only through a Smad-dependent pathway, but also through the regulation of the PI3K/Akt/β-catenin signaling axis.

Unlocking the Therapeutic Potential of Natural Products for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by memory loss and cognitive decline. With current treatments offering limited effectiveness, researchers are turning to natural products that can target various aspects of AD pathology. Clinically approved natural products, such as galantamine and huperzine A, have shown success in AD treatments. Furthermore, compounds such as epigallocatechin gallate, quercetin, and resveratrol are in clinical trials. This Perspective examines nearly 100 natural compounds with promising neuroprotective effects in preclinical and clinical studies. These compounds exhibit diverse pharmacological actions that help to prevent neurodegeneration while improving cognitive functions. Their unique structures further enhance their biological activities, making them promising candidates for drug discovery. This Perspective stresses the importance of further clinical research to maximize the medical benefits of these compounds and highlights their potential as innovative remedies for AD. Continued exploration of these compounds is crucial to fully leverage their capabilities in combating AD.

Influence of Radical Generation and Elimination on Sebum Production of Hamster Sebaceous Gland Cells

We focused on the effects of radical induction on cell differentiation and sebum production when antioxidants and oxidants were applied to normal hamster sebaceous gland cells. We also examined the relationship between sebum production and the reactive oxygen species (ROS) scavenging rate in these cells. Eight antioxidants (fullerene, epigallocatechin gallate, α-glucosylrutin, copper (II) gluconate, tannic acid, sodium copper-chlorophyllin, phytic acid, and ascorbyl tocopheryl phosphate) and one oxidant (hydrogen peroxide, H2O2) were used. The number of differentiated cells was determined by counting the viable cells, the intracellular triglyceride (TG) level was determined by separation and quantification by HPTLC, and the superoxide anion radical scavenging rate, nitric oxide scavenging rate, and H2O2 scavenging rate were also investigated. Adding various antioxidants decreased the differentiated cell number and TG content in the hamster sebaceous gland cells. Meanwhile, adding an oxidant (H2O2) increased the differentiated cell number and cellular TG. Pretreatment with antioxidants also prevented the oxidants from increasing the differentiated cell number and TG level. A strong correlation between the intracellular TG content and the H2O2 scavenging rate was identified. These results indicate that radical generation and scavenging are involved in sebum production in hamster sebaceous gland cells, and that the scavenging rate of H2O2 may be particularly important.

Green Tea's EGCG: Brewing Hope in the Battle against Breast Cancer

Breast cancer, a pervasive global malignancy, is anticipated to undergo a significant increase by 2040. Despite the conventional armamentarium of treatments including chemotherapy, radiation therapy, and surgery, the intricate landscape of breast cancer, characterized by its multifaceted surface receptors and signalling pathways, presents formidable challenges to treatment efficacy. Epigallocatechin-3-gallate (EGCG), extracted from Camellia sinensis, has emerged as a subject of interest due to its robust antioxidative properties stemming from its chemical structure. EGCG exerts its effects on pivotal stages of tumour growth and proliferation by modulating key signalling pathways such as MAPK, PI3K, NFkB, and ERK1/2 influencing apoptosis and cell cycle regulation. Clinical trials have provided insights into EGCG's potential impact on breast cancer such as mammographic density and pharmacokinetics, indicating its potential as a potent therapeutic agent. Moreover, when administered with conventional chemotherapy, EGCG demonstrates synergistic effects, enhancing therapeutic outcomes. Nevertheless, further research is warranted to validate the safety and efficacy of EGCG in breast cancer prevention and treatment.

Interpreting the role of epigallocatechin-3-gallate in Epstein-Barr virus infection-mediated neuronal diseases.

The increasing prevalence of neurodegenerative diseases is a formidable task due to their multifactorial causation and treatments limited to disease maintenance and progression. Epstein-Barr virus (EBV) is reported to be involved with neuropathologies; previous studies from our group suggested the effective binding of epigallocatechin-3-gallate (EGCG) with EBV nuclear antigen 1 (EBNA1) and glycoprotein H (gH). Therefore, in the current study, we evaluated the anti-EBV effect of ECGG on the neuronal cells. EBV-GFP exhibited a decline after EGCG treatment. We have observed a decrease in specific latent and lytic cycle genes. EBNA1 unravelled attenuation at day 1 (D1), whereas EBNA3B, EBNA3C, BMRF1, BZLF1, and gp350 showed major downregulation in D3 compared to EBV infection. Notably, EBNA-LP has shown mitigation in both the considered time points. Inflammatory and chemokine moieties like IL-6, CCR1, CCR3, and CCR5 declined upon EGCG treatment, while IL-10 exhibited elevation. Transcription factor STAT3 and NF-kB were decreased, especially in the pre-EGCG treated samples. Subsequently, restoration in the mitochondrial membrane potential was observed after EGCG treatment. We observed an increase in the mitochondrial fission genes like DRP1 and MiD49, and not many regulations were observed in the mitochondrial fusion genes except MFN2. Furthermore, the CytC, CytC oxidase, MAVS, ANT, and SDH exhibited elevation upon EGCG treatment, while ATPsyn and ABAD showed downregulation. Dysfunction of mitochondria is further related to apoptosis of neurons. Herein, we were keen to examine the level of amyloid-precursor protein (APP), and it has also indicated declined after EGCG treatment. Altogether, the current study demonstrated the anti-EBV effect of EGCG by subsiding the EBV-mediated inflammation and amendments in the neuropathological markers.

Injectable, Biodegradable and Photothermal Hydrogel with Quorum Sensing Inhibitory Effects for Subcutaneous Fungal Infection Treatment.

Owing to the high invasion depth and easy formation of biofilms, the treatment of subcutaneous fungal infection is intractable and challenging. Herein, we report an injectable and biodegradable hydrogel with bactericidal, quorum sensing inhibition and antioxidant activities for the in situ treatment of subcutaneous fungal infection. The hydrogel (BEPE) was constructed by irradiating mixed bovine serum albumin (BSA), ε-polylysine and epigallocatechin gallate (EGCG)-loaded mesoporous polydopamine (PDA) under near-infrared (NIR) light. BEPE exerted microbicidal effects against Candida albicans (99.5%) and Streptococcus mutans (99.6%) through synergistic photothermal effects and the microbiocidal activity of slowly released ε-polylysine. Moreover, the gently released EGCG from BEPE with relatively high bioavailability, synergistically inhibited and destroyed biofilms by inhibiting quorum sensing between microbes, resulting in an antibiofilm efficiency of 80.5% against C. albicans. An in vivo subcutaneous fungal infection study revealed that BEPE accelerates tissue regeneration via targeted formation, elimination of fungal infection and alleviation of inflammation in situ, thereby promoting wound healing. This biodegradable hydrogel strategy will facilitate the design of multifunctional microbicidal agents for targeted subcutaneous fungal infection treatment.

Biodegradable Polymeric Microspheres with Enhanced Hemostatic and Antibacterial Properties for Wound Healing.

Hemostasis is the initial step in wound healing, yet significant challenges, such as massive bleeding and infection, often arise. In this study, we developed amphiphilic biodegradable polyester-based segmented polyurethane (SPU) microspheres modified with epigallocatechin gallate (EGCG)-Ag nanoparticles and calcium-alginate cross-linking shell, combining blood absorption with the pro-coagulation properties of Ca2+ and the negative charge of EGCG for synergistic hemostatic effects across various stages of the coagulation cascade. The in vitro blood clotting time of the SPU@EAg@CaAlg microsphere (328.7 s) was reduced by half compared to the SPU microsphere (685.0 s). SPU@EAg@CaAlg exhibited a reduced hemostatic time and blood loss in three rat hemostatic models. Additionally, EGCG-Ag nanoparticles imparted strong antibacterial and anti-inflammatory properties both in vitro and in vivo. In vivo infected wound model demonstrated that SPU@EAg@CaAlg effectively eliminated bacteria and reduced the levels of pro-inflammatory factors, thereby promoting wound healing. Thus, the modified SPU microspheres present a promising candidate for effective hemostatic applications.

Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation

Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation

Epigallocatechin 3-gallate-induced neuroprotection in neurodegenerative diseases: molecular mechanisms and clinical insights.

Neurodegenerative diseases (NDs) are caused by progressive neuronal death and cognitive decline. Epigallocatechin 3-gallate (EGCG) is a polyphenolic molecule in green tea as a neuroprotective agent. This review evaluates the therapeutic effects of EGCG and explores the molecular mechanisms that show its neuroprotective properties. EGCG protects neurons in several ways, such as by lowering oxidative stress, stopping Aβ from aggregation together, changing cell signaling pathways, and decreasing inflammation. Furthermore, it promotes autophagy and improves mitochondrial activity, supporting neuronal survival. Clinical studies have demonstrated that EGCG supplementation can reduce neurodegenerative biomarkers and enhance cognitive function. This review provides insights into the molecular mechanisms and therapeutic potential of EGCG in treating various NDs. EGCG reduces oxidative stress by scavenging free radicals and enhancing antioxidant enzyme activity, aiding neuronal defense. It also protects neurons and improves cognitive abilities by inhibiting the toxicity and aggregation of Aβ peptides. It changes important cell signaling pathways like Nrf2, PI3K/Akt, and MAPK, which are necessary for cell survival, cell death, and inflammation. Additionally, it has strong anti-inflammatory properties because it inhibits microglial activation and downregulates pro-inflammatory cytokines. It improves mitochondrial function by reducing oxidative stress, increasing ATP synthesis, and promoting mitochondrial biogenesis, which promotes neurons' survival and energy metabolism. In addition, it also triggers autophagy, a cellular process that breaks down and recycles damaged proteins and organelles, eliminating neurotoxic aggregates and maintaining cellular homeostasis. Moreover, it holds significant promise as an ND treatment, but future research should focus on increasing bioavailability and understanding its long-term clinical effects. Future studies should focus on improving EGCG delivery and understanding its long-term effects in therapeutic settings. It can potentially be a therapeutic agent for managing NDs, indicating a need for further research.

Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and excessive cytokine production. This study aimed to explore the potential of Camellia sinensis L. water extract (CSE) as a treatment for AD by the impact of CSE on inflammatory responses in keratinocytes, particularly concerning the production of inflammatory cytokines and the modulation of signaling pathways relevant to AD pathogenesis. CSE was obtained via hot water extraction from Camellia sinensis L. Ultra-high-performance liquid chromatography (UPLC) analyzed catechin and caffeine content. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), polyphenol and flavonoid content were determined. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay measured antioxidant activity. Enzyme-Linked Immunosorbent Assay (ELISA), western blotting, and Immunofluorescence (IF) assays examined cytokines, pathways, and protein localization, respectively. Molecular docking assessed compound binding with inflammation-related proteins. UPLC identified six CSE components including epigallocatechin (EGC) epicatechin (EC), caffeine (CF), catechin (C), epigallocatechin gallate (EGCG), and epicatechin gallate (ECG). CSE demonstrated a significant reduction in the production of inflammatory cytokines interleukin (IL)-2 and IL-6 in TNF-α/IFN-γ activated keratinocytes. Treatment with CSE inhibited the mitogen-activated protein kinase (MAPK) pathway, which resulted in decreased phosphorylation of p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Exposure of TNF-α/IFN-γ- stimulated human keratinocytes (HaCaT) cells to CSE resulted in a 200 µg/mL dependent inhibition of p65 and signal transducer and activator of transcription 1 (STAT-1) translocation from the cytosol to the nucleus, as confirmed through immunofluorescence (IF) staining. Molecular docking simulations provided insights into the underlying mechanisms of CSE action, which supported its potential as a therapeutic agent for AD. CSE might be a potential candidate for its therapeutic efficacy for inflammatory skin conditions like AD. Thus, based on this evidence, the authors suggest that CSE should be studied further for its anti-inflammatory activities and topical application in the treatment of AD.

(-)-Epigallocatechin-3-Gallate and Quercetin Inhibit Quiescin Sulfhydryl Oxidase 1 Secretion from Hepatocellular Carcinoma Cells.

Liver cancer is one of the most prevalent cancers worldwide. The first-line therapeutic drug sorafenib offers only a moderate improvement in patients' conditions. Therefore, an approach to enhancing its therapeutic efficacy is urgently needed. It has been revealed that hepatocellular carcinoma (HCC) cells with heightened intracellular quiescin sulfhydryl oxidase 1 (QSOX1) exhibit increased sensitivity to sorafenib. QSOX1 is a secreted disulfide catalyst, and it is widely recognized that extracellular QSOX1 promotes the growth, invasion, and metastasis of cancer cells through its participation in the establishment of extracellular matrix. Inhibiting QSOX1 secretion can increase intracellular QSOX1 and decrease extracellular QSOX1. Such an approach would sensitize HCC cells to sorafenib but remains to be established. Since (-)-epigallocatechin-3-gallate (EGCG) has been demonstrated to be an effective inhibitor of α-fetal protein secretion from HCC cells, we screened QSOX1 secretion inhibition using polyphenolic compounds. We examined eight dietary polyphenols (EGCG, quercetin, fisetin, myricetin, caffeic acid, chlorogenic acid, resveratrol, and theaflavin) and found that EGCG and quercetin effectively inhibited QSOX1 secretion from human HCC cells (HepG2 or Huh7), resulting in high intracellular QSOX1 and low extracellular QSOX1. The combination of EGCG or quercetin, both of which change the cellular distribution of QSOX1, with sorafenib, which has no influence on the cellular distribution of QSOX1, exhibited multiple synergistic effects against the HCC cells, including the induction of apoptosis and inhibition of invasion and metastasis. In conclusion, our current results suggest that dietary EGCG and quercetin have the potential to be developed as adjuvants to sorafenib in the treatment of HCC by modulating the cellular distribution of QSOX1.

Bioinspired Assembly of Natural Polyphenol-Amino Acid Surfactants as Multifunctional Durable Coatings for Anticorrosion Fruit Packaging.

Challenges emerge in the quest for highly efficient and biocompatible coatings to tackle microbial contamination. Here, we propose a bioinspired paradigm combining (-)-epigallocatechin gallate (EGCG) and l-arginine surfactants (LAM) as all-green building blocks for advanced coatings with superior performance. Molecular dynamics simulations reveal the natural assembly process of the EGCG/LAM supramolecular nanoparticles (ELA NPs). Notably, the coatings retain 99.0% antimicrobial activity even after eight cycles of use and exhibit highly adhesive and anti-water washing properties, maintaining their efficacy after eight uses and 30 days of water soaking on various substrates. When applied as sustainable food packaging coatings for perishable fruits at room temperature, the ELA coatings significantly extend the shelf life of strawberries and cherry tomatoes, reducing weight loss and maintaining firmness and sweetness. This study demonstrates the potential of ELA NPs as versatile and durable coating materials for mitigating food waste and agricultural economic losses due to microbial pollution.

Incredible use of plant-derived bioactives as anticancer agents.

Cancer is a major global concern. Despite considerable advancements in cancer therapy and control, there are still large gaps and requirements for development. In recent years, various naturally occurring anticancer drugs have been derived from natural resources, such as alkaloids, glycosides, terpenes, terpenoids, flavones, and polyphenols. Plant-derived substances exhibit their anticancer potential through antiproliferative activity, cytotoxicity, apoptosis, angiogenesis and cell cycle arrest. Natural compounds can affect the molecular activity of cells through various signaling pathways, like the cell cycle pathway, STAT-3 pathway, PI3K/Akt, and Ras/MAP-kinase pathways. Capsaicin, ouabain, and lycopene show their anticancer potential through the STAT-3 pathway in breast, colorectal, pancreatic, lung, cervical, ovarian and colon cancers. Epigallocatechin gallate and emodin target the JNK protein in skin, breast, and lung cancers, while berberine, evodiamine, lycorine, and astragalin exhibit anticancer activity against breast, liver, prostate, pancreatic and skin cancers and leukemia through the PI3K/Akt and Ras/MAP-kinase pathways. In vitro/in vivo investigations revealed that secondary metabolites suppress cancer cells by causing DNA damage and activating apoptosis-inducing enzymes. After a meticulous literature review, the anti-cancer potential, mode of action, and clinical trials of 144 bioactive compounds and their synthetic analogues are included in the present work, which could pave the way for using plant-derived bioactives as anticancer agents.

Regulation of Bone Remodeling by Metal-Phenolic Networks for the Treatment of Systemic Osteoporosis.

Osteoporosis is a systemic metabolic disease that impairs bone remodeling by favoring osteoclastic resorption over osteoblastic formation. Nanotechnology-based therapeutic strategies focus on the delivery of drug molecules to either decrease bone resorption or increase bone formation rather than regulating the entire bone remodeling process, and osteoporosis interventions suffer from this limitation. Here, we present a multifunctional nanoparticle based on metal-phenolic networks (MPNs) for the treatment of systemic osteoporosis by regulating both osteoclasts and osteoblasts. In the osteoporotic microenvironment, the MPN nanoparticles degrade and trigger the release of bioactive metals (strontium ions, SrII) to promote osteogenesis and functionalized phenols (epigallocatechin gallate, EGCG) to suppress osteoclastogenesis. Injecting these nanoparticles into the tail vein of an ovariectomized mouse model, trabecular bone loss has been significantly prevented in the femoral head and vertebrae, along with increased trabecular bone volume and decreased trabecular bone separation. Overall, this work represents a versatile approach to explore MPN nanomaterials for the treatment of systemic osteoporosis and related orthopedic diseases.

Green Tea Polyphenol Epigallocatechin Gallate Interactions with Copper-Serum Albumin.

Epigallocatechin gallate (EGCg), an abundant phytochemical in green tea, is an antioxidant that also binds proteins and complex metals. After gastrointestinal absorption, EGCg binds to serum albumin in the hydrophobic pocket between domains IIA and IIIA and overlaps with the Sudlow I site. Serum albumin also has two metal binding sites, a high-affinity N-terminal site (NTS) site that selectively binds Cu(II), and a low-affinity, less selective multi-metal binding site (MBS). We proposed to determine whether EGCg binds or reacts with Cu(II)-serum albumin using fluorescence, UV-Visible and electron paramagnetic resonance (EPR) spectroscopy. Our results suggest that when serum albumin is loaded with Cu(II) in both sites, EGCg binds to the MBS-Cu(II) and reduces the copper to Cu(I). EGCg does not bind to or react with Cu(II) in the high-affinity NTS site. Potential consequences include changes in copper homeostasis and damage from pro-oxidative Fenton reactions.

The Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation for the Management of Obesity and Non-Alcoholic Fatty Liver Disease: Recent Updates.

Epigallocatechin gallate (EGCG) is the predominant bioactive catechin in green tea, and it has been ascribed a range of beneficial health effects. Current increases in obesity and non-alcoholic fatty liver disease (NAFLD) rates represent a persistent and burdensome threat to global public health. While many clinical studies have demonstrated that EGCG is associated with positive effects on various health parameters, including metabolic biomarkers, waist circumference, and body weight when consumed by individuals affected by obesity and NAFLD, there are also some reports suggesting that it may entail some degree of hepatotoxicity. The present review provides a comprehensive summary of the extant clinical findings pertaining to the safety and effectiveness of EGCG in managing obesity and NAFLD, with a particular focus on how treatment duration and dose level affect the bioactivity of this compound.

Multifunctional Nanomedicine for Targeted Atherosclerosis Therapy: Activating Plaque Clearance Cascade and Suppressing Inflammation.

Atherosclerosis (AS) is a prevalent inflammatory vascular disease characterized by plaque formation, primarily composed of foam cells laden with lipids. Despite lipid-lowering therapies, effective plaque clearance remains challenging due to the overexpression of the CD47 molecule on apoptotic foam cells, inhibiting macrophage-mediated cellular efferocytosis and plaque resolution. Moreover, AS lesions are often associated with severe inflammation and oxidative stress, exacerbating disease progression. Herein, we introduce a multifunctional nanomedicine (CEZP) targeting AS pathogenesis via a "cell efferocytosis-lipid degradation-cholesterol efflux" paradigm, with additional anti-inflammatory properties. CEZP comprises poly(lactic-co-glycolic acid) nanoparticles encapsulated within a metal-organic framework shell coordinated with zinc ions (Zn2+) and epigallocatechin gallate (EGCG), enabling CpG encapsulation. Upon intravenous administration, CEZP accumulates at AS plaque sites, facilitating macrophage uptake and orchestrating AS treatment through synergistic mechanisms. CpG enhances cellular efferocytosis, Zn2+ promotes intracellular lipid degradation, and EGCG upregulates adenosine 5'-triphosphate-binding cassette transporters for cholesterol efflux while also exhibiting antioxidant and anti-inflammatory effects. In vivo validation confirms CEZP's ability to stabilize plaques, reduce lipid burden, and modulate the macrophage phenotype. Moreover, CEZP is excreted from the body without safety concerns, offering a low-toxicity nonsurgical strategy for AS plaque eradication.