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Epigallocatechin gallate (EGCG) has demonstrated potential effects on obesity-induced precocious puberty, but the underlying mechanisms remain unclear. Female mice were randomly assigned into control (CON), EGCG-treated (EGCG), high-fat diet (HFD), and HFD with EGCG treatment (HFDEGCG) groups. Key measurements included body weight, vaginal opening time, and serum sex hormone levels. The gut microbiota was analyzed through 16S rRNA sequencing, fecal metabolites were assessed via metabolomics, and the hypothalamic transcriptome was examined using RNA sequencing. EGCG mitigated weight gain and delayed vaginal opening in mice with obesity-induced precocious puberty. Additionally, it reduced serum estradiol levels and decreased the number of mature ovarian follicles in the HFDEGCG group compared to the HFD group. EGCG treatment partially reversed HFD-induced dysbiosis by increasing the abundance of beneficial bacteria such as Akkermansia . Metabolomic analysis revealed significant alterations in tryptophan metabolism, while transcriptome analysis identified genes involved in metabolic pathways. Correlation analyses underscored the importance of the gut-brain axis in mediating EGCG's effects. Overall, EGCG prevents obesity-induced precocious puberty by modulating the gut microbiota, altering metabolic pathways, and regulating hypothalamic gene expression.

Probiotics have considerable interest due to their inseparable link to human health. However, probiotic products are seriously challenged during processing, preservation, and intake. Food-grade probiotic delivery systems need to be further explored as an effective way to enhance cell viability. In this study, water-in-oil (W/O) Pickering emulsions were fabricated by adding candelilla wax (CLW) as a network stabilizer based on acylated EGCG derivatives in the crystalline form as a Pickering stabilizer. The effects of acylated EGCG derivatives' concentration, CLW concentration, and oil phase volume fraction on the droplet size distribution, microstructure, and physical stability of Pickering emulsions were explored. The presence of CLW reduced the particle size and improved the physical stability of acylated EGCG-based emulsions, and the effect was more positive with increasing concentration. The protective effect of emulsions with different oil phase volume fractions on Lactobacillus plantarum during freeze-thaw cycles, storage, and gastrointestinal digestion was evaluated. The outer-phase physical barrier of W/O emulsions co-stabilized with acylated EGCG derivatives and CLW facilitated the sensitivity of probiotics to ice crystal growth, temperature changes, acidic environments, and digestive enzymes. The emulsions formulated with 40% oil phase volume fractions allowed Lactobacillus plantarum to survive up to 7.75 log CFU g -1 in the harsh gastrointestinal environment. The results offer promising strategies for applying W/O emulsion probiotic delivery systems in food processing, storage, and oral administration.

Tea polyphenols have a regulatory effect on metabolic-related diseases, however, the underlying mechanism remains elusive. Our study aims to explore the dietary intervention effect of Epigallocatechin gallate (EGCG), the major polyphenol in green tea, on obesity and intestinal barrier disorders in mice fed a high-fat diet. By supplementing with 50 mg kg -1 EGCG, we observed a significant amelioration in body weight gain, fat accumulation, and liver dysfunction. Furthermore, EGCG modulated the HFD-induced metabolomic alterations. In particular, EGCG intervention restored the ileal barrier by enhancing the expression of tight junction proteins and antimicrobial peptides. At the mechanistic level, EGCG treatment stabilized hypoxia-inducible factor 1α (HIF1α) both in vitro and in vivo . Meanwhile, EGCG significantly increased the abundance of Dubosiella and Akkermansia , along with the elevated SCFA contents. These findings suggest that the ability of EGCG to stabilize HIF1α and regulate specific gut microbes is pivotal in mitigating ileal barrier dysfunction and obesity. Moreover, serum metabolomics revealed potential biomarkers following EGCG intervention. This study supports the intake of EGCG or green tea in obesity management and offers a novel perspective for investigating the metabolic regulatory mechanism of other dietary polyphenols.

Dental caries is a chronic and destructive disease and matrix metalloproteinase-2 (MMP-2) plays a major role in caries. The inhibitory mechanisms of theaflavins [theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B), and theaflavin-3,3'-digallate (TF3)] on MMP-2 were investigated using techniques such as enzyme inhibition kinetics, multi-spectral methods, molecular docking, and molecular dynamics simulations. The results showed that TF1, TF2A, TF2B, and TF3 all competitively and reversibly inhibited MMP-2 activity. Fluorescence spectra and molecular docking indicated that four theaflavins spontaneously bind to MMP-2 through noncovalent interactions, driven by hydrogen bonds and hydrophobic interactions, constituting a static quenching mechanism and resulting in an altered tryptophan residue environment around MMP-2. Molecular dynamic simulations demonstrated that four theaflavins can form stable, compact complexes with MMP-2. In addition, the order of theaflavins' ability to inhibit MMP-2 was found to be TF1 > TF2B > TF2A > TF3. Interestingly, the order of binding capacity between MMP-2 and TF1, TF2A, TF2B, and TF3 was consistent with the order of inhibitory capacity, and was opposite to the order of steric hindrance of theaflavins. This may be due to the narrow space of the active pocket of MMP-2, and the smaller the steric hindrance of theaflavins, the easier it is to enter the active pocket and bind to MMP-2. This study provided novel insights into theaflavins as functional components in the exploration of natural MMP-2 inhibitors.

In this study, it was found that epigallocatechin-3-gallate (EGCG) could extend the lifespan of Caenorhabditis elegans ( C. elegans ) induced by 100 μM acrolein (ACR) at all test concentrations (300, 400, 500, 600, and 700 μM). Notably, 500 μM EGCG exhibited the most significant mean lifespan extension, increasing it by approximately 32.5%. Furthermore, 500 μM EGCG effectively reduced elevated levels of reactive oxygen species (ROS) and lipofuscin production caused by acrolein. It also bolstered the activity of antioxidant enzymes and mitigated malondialdehyde (MDA) levels compared to the ACR-only group. These effects appeared independent of dietary restrictions. Additionally, qPCR results revealed different changes in the transcription levels of 11 genes associated with antioxidative and anti-aging functions following EGCG treatment. At the expression level, GST-4::GFP, SOD-3::GFP and HSP-16.2::GFP exhibited an initial increase with ACR treatment followed by a decrease with EGCG treatment, while the expression pattern of these three GFPs remained consistent with the enzyme activity and transcription regulation level. EGCG treatment also reduced the nuclear localization of SKN-1 and DAF-16 in the MAPK and IIS pathways that were enhanced by ACR. Moreover, the longevity-promoting effects of EGCG were diminished or absent in 13 longevity gene-deletion mutants. In conclusion, EGCG demonstrates protective effects on ACR-induced C. elegans , with the IIS and MAPK pathways playing a critical role in enhancing resilience to ACR.

Epigallocatechin gallate (EGCG), a prominent bioactive compound found in tea, offers numerous health benefits. Previous studies have highlighted its potential in mitigating hyperuricemia. In this study, hyperuricemic mice induced by potassium oxonate (PO) were treated with EGCG or the anti-hyperuricemia medication allopurinol (AP) to investigate the mechanisms underlying their anti-hyperuricemic effects. The results demonstrated that both EGCG and AP significantly reduced serum uric acid (UA) levels. Further analysis revealed that EGCG promoted the expression of UA secretion transporter genes ( Oat1 and Oct1 ) while inhibiting the expression of UA reabsorption transporter genes ( Urat1 and Glut9 ) in the kidney. By 16S rDNA sequencing, EGCG, but not AP, was found to alter the composition of the gut microbiota. Notably, EGCG induced significant changes in the relative abundance of specific bacteria such as Lactobacillus , Faecalibaculum , and Bifidobacterium , which displayed high correlations with serum UA levels and UA-related gene expression. Metabolomic analysis suggested that EGCG-induced modifications in bacterial metabolites might contribute to the alleviation of hyperuricemia. Transcriptomic analysis of the intestinal epithelium identifies 191 differentially expressed genes (DEGs) in EGCG-treated mice, including 8 purine-related genes. This study elucidates the anti-hyperuricemic mechanisms of EGCG, particularly its influence on the gut microbiota and gene expression in the intestinal epithelium.

Catechol- O -methyltransferase (COMT) plays a central role in the metabolic inactivation of endogenous neurotransmitters and xenobiotic drugs and hormones having catecholic structures. Its inhibitors are used in clinical practice to treat Parkinson's disease. In this study, a fluorescence-based visualization inhibitor screening method was developed to assess the inhibition activity on COMT both in vitro and in living cells. Following the screening of 94 natural products, Pu-erh tea extract exhibited the most potent inhibitory effect on COMT with an IC 50 value of 0.34 μg mL -1 . In vivo experiments revealed that Pu-erh tea extract substantially hindered COMT-mediated levodopa metabolism in rats, resulting in a significant increase in levodopa levels and a notable decrease in 3- O -methyldopa in plasma. Subsequently, the chemical components of Pu-erh tea were analyzed using UHPLC-Q-Exactive Orbitrap HRMS, identifying 24 major components. Among them, epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, and catechin gallate exhibited potent inhibition of COMT activity with IC 50 values from 93.7 nM to 125.8 nM and were the main bioactive constituents in Pu-erh tea responsible for its COMT inhibition effect. Inhibition kinetics analyses and docking simulations revealed that these compounds competitively inhibit COMT-mediated O -methylation at the catechol site. Overall, this study not only explained how Pu-erh tea catechins inhibit COMT, suggesting Pu-erh tea as a potential dietary intervention for Parkinson's disease, but also introduced a new strategy for discovering COMT inhibitors more effectively.

Changes in the chemical composition of white tea during storage have been studied extensively; however, whether such chemical changes impact the efficacy of white tea in ameliorating colitis remains unclear. In this study, we compared the effects of new (2021 WP) and 10-year-old (2011 WP) white tea on 3% dextrose sodium sulfate (DSS)-induced ulcerative colitis in mice by gavaging mice with the extracts at 200 mg kg -1 day -1 . Chemical composition analysis showed that the levels of 50 compounds, such as flavanols, dimeric catechins, and amino acids, were significantly lower in the 2011 WP extract than in the 2021 WP extract, whereas the contents of 21 compounds, such as N -ethyl-2-pyrrolidinone-substituted flavan-3-ols, theobromine, and (-)-epigallocatechin-3-(3''- O -methyl) gallate, were significantly higher. Results of the animal experiments showed that 2011 WP ameliorated the pathological symptoms of colitis, which was superior to the activity of 2021 WP, and this effect was likely enhanced based on the decreasing of the relative abundance of the g_bacteroides and g_Escherichia-Shigella flora in mice with colitis and promoting the conversion of primary bile acids to secondary bile acids in the colon. These results will facilitate the development of novel functional products from white tea.

Green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG) has been well studied for its biological activities in the prevention of chronic diseases. However, the biological activities of EGCG oxidation-derived polymers remain unclear. Previously, we found that these polymers accumulated in intraperitoneal tissues after intraperitoneal injection and gained an advantage over native EGCG in increasing insulin sensitivity via regulating the renin-angiotensin system (RAS) in type 2 diabetic mice. The present study determined the pro-apoptosis activities and anticancer mechanisms of the EGCG oxidation-derived polymer preparation (the >10 kDa EGCG polymers) in digestive tract cancer cells. Upon incubation of the >10 kDa EGCG polymers with CaCo2 colon cancer cells, these polymers coated the cell surface and regulated multiple components of the RAS in favor of cancer inhibition, including the downregulation of angiotensin-converting enzyme (ACE), angiotensin-II (AngII) and AngII receptor type 1 (AT1R) in the pro-tumor axis, as well as the upregulation of angiotensin-converting enzyme 2 (ACE2) and angiotensin1-7 (Ang(1-7)) in the anti-tumor axis. The treatment also markedly increased angiotensinogen (AGT), which is the precursor of the angiotensin peptides. The regulation of these RAS components occurred prior to apoptosis. Similar pro-apoptotic mechanisms of the >10 kDa EGCG polymers, were also observed in TCA8113 oral cancer cells. The >10 kDa EGCG polymers exhibited compromised activities in scavenging or initiating reactive oxygen species compared to EGCG, but gained a higher reactivity toward sulfhydryl groups, including protein cysteine thiols. We propose that the polymers bind onto the cell surface and regulate multiple RAS components by reacting with the sulfhydryl groups on the ectodomains of transmembrane proteins.

(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol in tea and exerts several health-promoting effects. It easily autoxidizes into complex polymers and becomes deactivated due to the presence of multiple phenolic hydroxyl structures. Nonetheless, the morphology and biological activity of complex EGCG polymers are yet to be clarified. The present study demonstrated that EGCG autoxidation self-assembled nanoparticles (ENPs) exhibit antioxidant activity in vitro and hepatic REDOX homeostasis regulation activity in vivo . Also, the formation of ENPs during the EGCG autoxidation process was based on the intermolecular interaction forces that maintain the stability of the nanoparticles. Similar to EGCG, ENPs are scavengers of reactive oxygen species and hydroxyl radicals in vitro and also regulate hepatic REDOX activity through liver redox enzymes, including thioredoxin reductase (TrxR), thioredoxin (Trx), glutathione reductase (GR), glutaredoxin (Grx), and glutathione S-transferase (GST) in vivo. Moreover, ENPs activate the NRF2 antioxidant-responsive element pathway, exerting a detoxification effect at high doses. Unlike EGCG, ENPs do not cause liver damage at low doses and also maintain liver biosafety at high doses through self-assembly, forming large particles, which is supported by the unchanged levels of liver damage biomarkers, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver γ-phosphorylated histone 2AX (γ-H2AX), and P53-related genes ( Thbs , MDM2 , P53 , and Bax ). Collectively, these findings revealed that ENPs, with adequate biosafety and regulation of hepatic redox activity in vivo , may serve as substitutes with significant potential for antioxidant applications or as food additives to overcome the instability and liver toxicity of EGCG.

This study investigated the influence of carrier oils on the in vitro and in vivo bioavailability of PTE encapsulated in scallop gonad protein isolates (SGPIs)-epigallocatechin gallate (EGCG) conjugate stabilized emulsions. The SGPIs-EGCG stabilized emulsions were subjected to an in vitro simulated digestion, and the resulting corn oil and MCT micelles were used to evaluate the PTE transportation using the Caco-2 cell model. Both emulsions remarkably improved the bioaccessibility of PTE in the micelle phase. Nevertheless, corn oil emulsions increased trans-enterocyte transportation of PTE more efficiently than MCT emulsions. Furthermore, the maximum plasma concentrations of PTE and its metabolites in mice fed with PTE emulsions were prominently higher than those in mice fed with PTE solution, while the in vivo metabolic patterns of PTE in different oil-stabilized emulsions were different. Therefore, SGPIs-EGCG stabilized emulsions could enhance the bioavailability of PTE through controlled release, in which corn oil is more suitable than MCT.

The concept of "synergy" and its applications has rapidly increased in the food industry as a practical strategy to preserve and improve health-promoting effects of the functional ingredients. In this study, hydrophilic epigallocatechin-3-gallate (EGCG) and lipophilic lycopene (LYC) were loaded separately (EGCG loaded PDE (PE), and LYC loaded PDE (PL), and also co-delivered (PEL) within a pickering double emulsion (PDE) system to induce synergistic hypolipidemic effect. Their effects on the serum lipid profile, weight of tissue fats, liver lipid droplet accumulation, and liver steatosis in a high-fat diet rat model were investigated. Moreover, different pathways (HMG-CoR, LDL-R, PPARγ and AMPK) involved in triggering hypolipidemic effects were verified at both mRNA and protein levels. The study's findings showed that inclusion of EGCG improved while LYC negatively affected the physical stability of PDE. The contents of total cholesterol and triacylglyceroles in serum and liver as well as the weight of tissue fats were substantially reduced in all groups (PE/PL/PEL). The alteration in absorption site of EGCG and enhanced bioaccessibility of LYC when delivered by PDE strengthened the hypolipidemic properties of PE and PL, mainly through triggering the pathways of HMG-CoR, LDL-R and PPARγ. Furthermore, the synergistic hypolipidemic effect of PEL was achieved mainly through the activation of the AMPK pathway.

Diabetes is a disease that is characterized by a disturbance of glucose metabolism. Theabrownin (TB) is one of the most active and abundant pigments in Pu-erh tea, and it is a brown pigment with multiple aromatic rings and attached residues of polysaccharides and proteins. TB has been shown to be hypolipidemic and displays fasting blood glucose (FBG)-lowering properties in rats fed a high-fat diet, but the underlying mechanism has not been elucidated. This study aimed to determine the effect of TB in treating diabetes and explore the underlying mechanism of action of intestinal microbes by using Goto-Kakizaki (GK) rats. Diabetic GK rats were treated up to 8 weeks with TB (GK-TB). Following treatment, the body weight, triglyceride (TG) content, fasting blood glucose (FBG) content, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were significantly lower in the GK-TB group than in the GK control group ( P < 0.05). Meanwhile, the circulating adiponectin (ADPN), leptin, and glucokinase levels in the serum of the GK-TB group were significantly higher than those in the GK group, while there was little difference in hepatic lipase (HL) and hormone-sensitive triglyceride lipase (HSL) enzyme activities ( P > 0.05). Furthermore, with the extension of treatment time, the number of unique intestinal microorganisms in GK rats greatly increased and an interaction among intestinal microorganisms was observed. The Firmicutes / Bacteroides ratio was decreased significantly, and the composition of Actinobacteria and Proteobacteria was increased. The use of multiple omics technologies showed that TB is involved in the targeted regulation of the core characteristic intestinal flora including Bacteroides thetaiotaomicron (BT), Lactobacillus murinus (LM), Parabacteroides distasonis (PD), and Bacteroides&#95;acidifaciens (BA) which improved the glucose and lipid metabolism of GK rats via the AMP-activated protein kinase signaling pathway, insulin signaling pathway, bile secretion and glycerophospholipid metabolism. Intragastric administration of BT, LM, PD, or BA led to a significantly reduced HOMA-IR in GK rats. Furthermore, BT significantly reduced serum lipid TG and total cholesterol (TC) and BA significantly reduced the serum lipid TC and low-density lipoprotein (LDL). PD significantly reduced serum LDL, while the effect of LM was not significant. However, LM and PD significantly increased the content of ADPN in serum. Taken together, our results indicated that the effect of TB on diabetic rats mainly depends on the targeted regulation of intestinal microorganisms and that TB is a functional food component with great potential to treat or prevent diabetes.

(-)-Epigallocatechin gallate (EGCG)-incorporated casein nanoparticles benefit from excellent antioxidant, anti-inflammatory and anti-cancer activities due to their synergistic efficiency, but few studies have evaluated their safety. In this study, the EGCG-casein nanoparticles (EGCG-NPs) formulated using caseinate by ultrasonic treatment were evaluated for their subacute toxicity. The subacute toxicity test of EGCG-NPs through 28-day oral administration in rats did not exhibit adverse effect, with a no-observed-adverse-effect level (NOAEL) of at least 5.0 g per kg body weight (BW) per day, which was equivalent to 500 mg per kg BW EGCG per day. However, the serum Na level in females and males treated with 10.0 g per kg BW EGCG-NPs increased significantly as compared to the control rats ( P < 0.05). Similar indications appeared in rats treated with 10.0 g per kg BW pure casein nanoparticles without EGCG, which indicated that high doses of caseinate nanoparticles result in an excess serum Na level. Therefore, we should consider the safety of the nanoparticle formulation of caseinate when it is used as a loading nutrient and a functional substance in foods.

Sodium alginate (SA) hydrogel beads have been extensively studied as delivery systems for bioactive compounds. Key challenges include overcoming the highly porous and poor emulsifying properties of SA hydrogels. Herein, soy protein isolate (SPI) was modified by covalent and noncovalent conjugation with epigallocatechin-3-gallate (EGCG), followed by complexation with SA to change the SA structure and fabricate hydrogel beads with low porosities. Microencapsulation beads were fabricated from SA-, SA/SPI-, and SA/SPI-modified EGCG complexes with a corn oil/quercetin mixture core. After the covalent and noncovalent SPI-modified EGCG complexes were combined with SA, the OH stretching vibration shifted, indicating that hydrogen bonds formed between the protein and SA, and the crystal structure of SA was destroyed. To achieve crosslinking, the beads were injected into a CaCl 2 solution, whereby Ca 2+ ions replaced the Na + ions in SA. Meanwhile, the addition of covalent and noncovalent SPI-modified EGCG complexes promoted the binding capacity of Ca 2+ and SA. All hydrogel beads possessed open-cell microstructures with interconnecting pores. The SA/SPI-modified EGCG hydrogel beads exhibited smoother surfaces, thicker shells, and lower porosity than the SA hydrogel beads. Moreover, they exhibited significantly higher antioxidant activities. During digestion, all types of hydrogel bead maintained their structure, and only a small part of the encapsulated oil and quercetin was digested in the upper part of the gastrointestinal tract. In short, the formation mechanism of hydrogel beads was clarified, and hydrogel beads with low porosity and high antioxidation activities were successfully fabricated.

Epigallocatechin gallate (EGCG) and β-lactoglobulin (βLg) were conjugated by covalent bonds to form EGCG-βLg conjugates. This conjugation causes structural and bioactivity changes in βLg, which in turn can be used as a possible approach for desensitization to allergens. In this study, the desensitization mechanism was investigated by monitoring βLg secondary structure and immunoglobulin E (IgE) combining capacity changes on the basis of the conjugation mechanism. Furthermore, the desensitization efficiency in vivo was evaluated through animal experiments. The results show that temperature influenced the conjugation by decreasing the binding affinities ( K a ) and binding numbers ( n ) of EGCG. The conjugation of EGCG decreased βLg's IgE combining capacity by decreasing the β-sheet component and imparted antioxidant properties by the introduction of hydroxyl groups. In addition, animal experiment results indicated that βLg induced significant changes in the levels of IgE and inflammatory cytokines, and the relative abundance of small intestinal flora, linked to the inflammatory lesions and anaphylaxis symptoms. EGCG-βLg conjugates can suppress the allergic response, attenuating serum IgE and relieving the anaphylaxis symptoms.

Cyclophosphamide (CTX) is an antitumor drug commonly used to treat various cancer types. Unfortunately, its toxic side effects, including gastrointestinal (GI) toxicity, affect treatment compliance and patients' prognosis. Thus, there is a critical need of evaluating strategies that may improve the associated GI toxicity induced by CTX. In this work, we evaluated the capacity of epigallocatechin-3-gallate (EGCG), a major constituent of green tea, to improve the recovery of gut injury induced by CTX in mice. Treatment with CTX for 5 days severely damaged the intestinal structure, increased immune-related cytokines (TNFα, IL-10 and IL-21), reduced the expression levels of tight junction proteins (ZO-1, occludin, claudin-1), induced reactive oxygen species, altered the composition of gut microbiota, and reduced short chain fatty acid levels. EGCG treatment, starting one day after the last CTX dose, significantly improved the intestinal structure, ameliorated gut permeability, and restored ZO-1, occludin and claudin-1 levels. Moreover, EGCG reduced TNFα, IL-10 and IL-21 levels and decreased oxidative stress by regulating the activities of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. Finally, EGCG treatment restored the composition of gut microbiota and the levels of the short chain fatty acids. In conclusion, these findings indicate that EGCG may function as an effective bioactive compound to minimize CTX-induced GI tract toxicity.

At the end of 2019, the COVID-19 virus spread worldwide, infecting millions of people. Infectious diseases induced by pathogenic microorganisms such as the influenza virus, hepatitis virus, and Mycobacterium tuberculosis are also a major threat to public health. The high mortality caused by infectious pathogenic microorganisms is due to their strong virulence, which leads to the excessive counterattack by the host immune system and severe inflammatory damage of the immune system. This paper reviews the efficacy, mechanism and related immune regulation of epigallocatechin-3-gallate (EGCG) as an anti-pathogenic microorganism drug. EGCG mainly shows both direct and indirect anti-infection effects. EGCG directly inhibits early infection by interfering with the adsorption on host cells, inhibiting virus replication and reducing bacterial biofilm formation and toxin release; EGCG indirectly inhibits infection by regulating immune inflammation and antioxidation. At the same time, we reviewed the bioavailability and safety of EGCG in vivo . At present, the bioavailability of EGCG can be improved to some extent using nanostructured drug delivery systems and molecular modification technology in combination with other drugs. This study provides a theoretical basis for the development of EGCG as an adjuvant drug for anti-pathogenic microorganisms.

(-)-Epicatechin gallate (ECG), as a compound in green tea extract polyphenols, has specific therapeutic effects against oxidative stress. Oxidative stress exists throughout the pathological development of atherosclerosis. In this study, two atherosclerosis models, oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) and high fat diet (HFD)-induced ApoE -/- mice, were applied to explore the mechanism of ECG intervention on AS. In vivo and in vitro studies showed that ECG reduced the level of MDA and increased the activity of SOD, which are oxidative stress factors. ECG also improved HFD-induced disorder of lipid factor expression in the serum of ApoE -/- mice and alleviated oxidative stress by enhancing the antioxidant activity. The potential mechanism was supposed to be the inhibition of the phosphorylation of p65 by ECG in the NF-κB pathway in the aorta, thereby blocking the expression of inflammatory mediators. In addition, ECG increased the stability of atherosclerosis plaques by reducing the expression of MMP-2 and ICAM-1 in atherosclerosis diseased tissues. ECG reduced lipid accumulation in the aorta and its roots and also plaque neoplasia. Western blotting experiments indicated that ECG increased the nuclear transfer of Nrf2 and the expression of heme oxygenase 1 (HO-1) was increased. These results demonstrated that ECG significantly reduced the formation of aortic plaque in ApoE -/- mice which was possibly triggered by the inhibition of hyperlipidemia and oxidative stress that exhibited the anti-atherosclerotic potential.

Caseinophosphopeptides (CPPs) are a group of bioactive polypeptides hydrolyzed from caseins. Theaflavin-3,3'-digallate (TF-3) is a characteristic biofunctional polyphenol in black tea. In the present study, the interactions between CPPs and TF-3 were systematically investigated with fluorescence quenching, quartz crystal microbalance with dissipation monitoring (QCM-D), circular dichroism (CD), and small-angle X-ray scattering (SAXS). Both fluorescence quenching and QCM-D studies demonstrated that TF-3 interacted with CPPs primarily through hydrogen bonding. Other forces were also involved. The addition of TF-3 did not change the secondary structures and the radius of gyration of CPPs, but it induced the aggregation of CPPs. The size of the aggregates increased with the concentration of TF-3. The impact of the association between TF-3 and CPPs on the antioxidant activity of TF-3 was studied by the cellular antioxidant activity (CAA) assay, which revealed that the cellular antioxidant activity of TF-3 was enhanced after binding to CPPs.

The co-encapsulation of multiple bioactive components in a carrier may produce synergistic effects and improve health benefits. In this study, the interactions of β-lactoglobulin (β-LG) with epigallocatechin-3-gallate (EGCG) and/or piceatannol (PIC)/oxyresveratrol (OXY) were investigated by multispectroscopic techniques, isothermal titration calorimetry, and molecular docking. The static quenching mechanism of β-LG by EGCG, PIC and OXY was confirmed by fluorescence spectroscopy and UV-vis absorption difference spectroscopy. The binding sites of these three polyphenols in β-LG were identified by site marking fluorescence experiments and molecular docking. The thermodynamic parameters of the β-LG + EGCG/PIC/OXY binary complex and β-LG + EGCG + PIC/OXY ternary complex were obtained from fluorescence data and used to analyze the main driving force for complex formation. The exothermic binding process was further confirmed by isothermal titration calorimetry. The α-helical content, particle size and morphology of free and ligand-bound β-LG were determined by circular dichroism spectroscopy, dynamic light scattering and transmission electron microscopy, respectively. The effect of EGCG, PIC and OXY on the conformation of β-LG was studied by Fourier transform infrared spectroscopy. In addition, the maximum synergistic antioxidant activity between EGCG and PIC/OXY was obtained by response surface analysis. The effects of β-LG in the binary and ternary systems on the antioxidant activity, stability, solubility and cytotoxicity of the polyphenols were also studied. Finally, the different cytotoxicities of the complexes and nanoparticles of the binary and ternary systems were compared. The results of this study are expected to provide a theoretical basis for the development of β-LG-based carriers co-encapsulating a variety of bioactive components.

Green tea has been considered as a health-promoting beverage and is widely consumed worldwide. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol derived from green tea leaves with potent antioxidative and chemopreventive activities, has been reported to offer protection against inflammation-driven tissue damage. Here, we evaluated the protective effects of EGCG against lung injury during acute pancreatitis (AP) and further revealed the detailed mechanism. The results showed that EGCG significantly attenuated l-arginine-induced AP and the consequent pulmonary damage in mice. Moreover, EGCG substantially attenuated oxidative stress and concurrently suppressed NOD-like receptor protein 3 (NLRP3) inflammasome activation in the lung. In vitro, EGCG considerably reduced the production of mitochondrial reactive oxygen species (mtROS) and oxidized mitochondrial DNA (ox-mtDNA) in alveolar macrophages (AMs) challenged with AP-conditioned plasma. Meanwhile, the amount of ox-mtDNA bound to NLRP3 decreased significantly by the treatment with EGCG, resulting in impaired NLRP3 inflammasome activation. In addition, the antagonism of NLRP3 signaling by EGCG was affected in the presence of the mtROS stimulant rotenone or scavenger Mito-TEMPO. Altogether, EGCG possesses potent activity to attenuate lung injury during AP progression by inhibiting NLRP3 inflammasome activation. As for the mechanism, the EGCG-conferred restriction of NLRP3 inflammasome activation probably arises from the elimination of mtROS as well as its oxidative product ox-mtDNA, which consequently enables the protection against AP-associated lung injury.

Epigallocatechin-3-gallate (EGCG) and caffeine constitute the most effective ingredients of weight loss in tea. However, whether combination of EGCG and caffeine exhibits anti-obesity synergy remains unclear. Here, we showed low-doses of EGCG and caffeine used in combination led to synergistic anti-obesity effects equivalent to those of high-dose EGCG. Furthermore, combination treatment exhibited a synergistic effect on altering gut microbiota, including decreased Firmicutes level and increased Bifidobacterium level. Other notable effects of combination treatment included synergistic effects on: increasing fecal acetic acid, propionic acid, and total SCFAs; decreasing expression of GPR43; and increasing microbial bile salt hydrolase gene copies in the gut, facilitating generation of unconjugated BAs and enhancing fecal BA loss. Additionally, combination treatment demonstrated synergistic effects toward increasing the expression of hepatic TGR5 and decreasing the expression of intestinal FXR-FGF15, resulting in increased expression of hepatic CYP7A1. Thus, the synergistic effect may be attributed to regulation of gut microbiota and BA metabolism.

The effect of non-cytotoxic doses of epigallocatechin-3-gallate (EGCG) on the metastatic capability of human hepatocellular carcinoma (HCC) cells was investigated in vitro and in vivo. miR483-3p, a microRNA whose expression correlates inversely with survival and positively with disease progression in HCC patients, was found to promote HCC cell migration and invasion in vitro as well as lung metastasis in nude mice established by the tail-vein injection of HCC cells. The induction of reactive oxygen species (ROS) and downregulation of antioxidant defense factors Nrf2 and SOD2 appeared to be an important underlying mechanism and treatment with a non-cytotoxic dose of EGCG effectively reversed the miR483-3p-induced enhancement of HCC cell migration and invasion in vitro. Moreover, administration through drinking water at doses (0.1% and 0.5% EGCG solution, respectively) equivalent to the intake of regular to heavy tea drinkers could also significantly inhibit lung metastasis of HCC cells based on the estimation from the USDA Database for the Flavonoid Content of Selected Foods and FDA guidelines for the conversion of animal dose to human equivalent dose. EGCG also significantly counteracted the miR483-3p-induced alteration in the expression of epithelial-mesenchymal transition (EMT) markers, E-cadherin and vimentin, and downregulated the endogenous expression of miR483-3p in HCC cells through an epigenetic mechanism that led to the hypermethylation of the miR483-3p promoter region. The data from our study illustrate that miR483-3p promotes HCC metastasis likely through the induction of oxidative stress and uncover a novel role of EGCG for protection against miR483-3p-mediated HCC metastasis via the epigenetic modulation of miR483-3p expression. These findings therefore provide further evidence supporting that regular tea consumption may contribute to protection against miR-483-3p-induced ROS and the associated HCC progression.

In this study, we evaluated the food matrix effects of chocolate on the absorption of green tea catechins (GTCs), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg), in five healthy 22-year-old women. In the single-intake experiment, the plasma concentrations of ECg (P < 0.05, at 1.5 h) and EGCg (P < 0.05, at 6 h) but not those of EC and EGC were reduced by the chocolate matrix. Regardless of the chocolate matrix, ECg and EGCg were mainly present as their aglycones in the plasma, whereas EGC and EC were found mostly as conjugated metabolites. After daily intake of GTCs mixed with chocolate for 14 days followed by overnight fasting, ECg but not EGCg was detected in the plasma. To compare the plasma profiles of ECg and EGCg, a mixture containing approximately equal amounts of ECg and EGCg was administered to nine rats for 14 days. Following treatment and overnight food deprivation, the plasma content of ECg was higher than that of EGCg. After a single injection of the same mixture in seven rats, ECg levels were higher than those of EGCg, and a greater amount of conjugated metabolites of ECg than those of EGCg was detected in the plasma 10 h after administration. In conclusion, the chocolate matrix affects the plasma profiles of GTCs, particularly ECg. ECg appears to persist in the plasma for a longer period, regardless of the chocolate matrix.

Green tea polyphenol epigallocatechin-3-gallate (EGCG) may help prevent metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its protective effects are complicated and remain unclear. With the gut-liver axis theory as a foundation, the present study investigated the effects of EGCG on intestinal mucosal immunity in male C57BL/6 mice fed a high-fat Western diet or the diet supplemented with 0.4% dietary EGCG (w/w) for 14 weeks. Dietary EGCG supplementation effectively prevented changes-including excessive accumulation of visceral and hepatic fat, abnormal liver function, and elevated concentrations of serum and liver inflammatory cytokines-known to be caused by high-fat diets. In addition, serum lipopolysaccharide concentrations decreased by 94.3%. RNA sequencing data of differentially expressed genes in ileal samples among three groups indicated that most of the pathways in the Kyoto Encyclopedia of Genes and Genomes in the first 20 enrichment levels were related to immunity and inflammatory reactions. Real-time reverse transcription quantitative polymerase chain reaction was used to determine alterations in expression levels of key genes related to intestinal immune function and inflammatory responses from ileal and colonic samples. Changes in secretory immunoglobulin A in the small intestine, serum, and feces further demonstrated improved intestinal mucosal immunity in the EGCG-treated mice. In conclusion, dietary EGCG effectively prevented the development of NAFLD and significantly improved intestinal mucosal immunity in mice with obesity induced by a high-fat diet. However, whether improved intestinal immune function is the key mechanism underlying the health benefits of dietary EGCG warrants further research.

Renal fibrosis is a characteristic of diabetic nephropathy, which is a serious complication of diabetes. It has been reported that (-)-epigallocatechin gallate (EGCG) attenuates renal fibrosis. However, the molecular mechanism of regulation by EGCG in this process remains unclear. Previous studies showed that abnormal activation of Notch signaling contributes to the development of renal fibrosis. Previous studies have demonstrated that EGCG attenuates Notch1 expression. In this study, we found that the levels of fibronectin and Notch1 expression were decreased in human embryonic kidney cells after treatment with EGCG. We also observed that the type II transforming growth factor beta receptor (TGFβRII) and Smad3 pathway were inhibited in kidney cells by treatment with EGCG. In the diabetic kidney, we found that the activation of Notch signaling was attenuated by administration of EGCG. Moreover, TGFβRII and Smad3 phosphorylation could be inhibited by treatment with EGCG in the kidney. These results indicated that EGCG may improve renal fibrosis by targeting Notch via inhibition of the TGFβ/Smad3 pathway in diabetic mice. Our findings provide insight into the therapeutic strategy for diabetes-induced renal fibrosis, and suggest EGCG to be a novel potential medicine for the treatment of chronic kidney disease in patients with diabetes.

The rheological behavior, assembly measurements, thermal stability, molecular conformation, and molecular interactions of myofibrillar proteins (MP) modified by transglutaminase (TGase) and epigallocatechin-3-gallate (EGCG) were investigated. Fluorescence and ultraviolet spectra showed that TGase and ECCG quenched the endogenous fluorescence of MP and improved the exposure of chromophoric and hydrophobic groups of MP caused by unraveling the tertiary structure. TGase and EGCG treatment increased the α-helix and β-turn contents and the structure became more ordered. It also increased the thermal stability of MP and the storage modulus of MP gels as reflected in the rheological and thermal properties tests. Meanwhile, changes in SDS-PAGE, FT-IR, and sulfhydryl contents showed that TGase increased the disulfide bond contents, whereas it decreased after EGCG was added, suggesting that EGCG could react with MP via non-covalent and covalent interactions. Assembly measurements illustrated that TGase increased the turbidity and particle size of MP, while TGase and EGCG treatment accelerated MP aggregation and it was associated with the increase in the EGCG concentration, which was further confirmed by SEM and AFM. This work could contribute new insights into the synergistic effect of TGase and EGCG on modifying MP and guide for its application in surimi processing.

The aim of this study is to examine the antidepressant-like effect of EGCG and get deeper insights into implications of modulating serotonin (5-HT) in the colon and brain. A total of 24 stochastically-selected rats were subdivided into three groups: one group served as the control group, and other two groups were subjected to chronic unpredictable mild stress interventions (CUMS group and CUMS + EGCG group respectively). Before conducting a designed set of behavior tests, all rats were weighed and then forced swimming test (FST) and open field test (OPT) were performed in all rats for the measurement and analysis of central and colonic serotonin levels. In order to determine the extent of CUMS-induced injuries and examine neurological deficits, the method of Nissl staining was implemented accordingly. Meanwhile, haematoxylin-eosin (H&E) staining was employed to detect the structure of the colon. The study found that, due to the involvement of CUMS, the body weight of experimental rats declined, their time of immobility in FST was greater, and the avoidance of central sections in OPT was also greater and more obvious. However, through intervention of the EGCG treatment, either weight loss or depression-related behavior induced by the involvement of CUMS was alleviated in the experimental rats. Comparison of both CUMS and CUMS + EGCG groups indicated that EGCG administration may decrease the level of serotonin (5-HT) in the colon but increase the level of serotonin (5-HT) in the hippocampus. However, it should be noted that the level of 5-HT in peripheral blood did not show any significant difference between both groups. Furthermore, CUMS caused the morphological changes of the hippocampus and structural changes of the colon were noteworthy. Summarily, the investigation results of this experimental study indicated that the intervention of EGCG treatment might have considerable implications in several aspects such as anti-depression, regulation of 5-HT concentration, enhancement of intestinal hyper-permeability, and neuroprotection in the hippocampus.

The objective of this study was to investigate the effect of (-)-epigallocatechin (EGC; at 0, 10, and 100 μmol g-1 protein) coupled with sodium tripolyphosphate (STP) on the in vitro digestibility and emulsion gel properties of myofibrillar protein (MP) under oxidative stress. The addition of both EGC and STP inhibited protein carbonyl formation but promoted the loss of thiol and free amine groups. Combined with the results of tryptophan fluorescence, surface hydrophobicity, electrophoresis, and solubility, the presence of STP enhanced the covalent reactions between the quinone of EGC and the thiols and free amines of MP. The combination of EGC at 10 μmol g-1 and STP increased the protein digestion rate in the gastric tract and contributed to an improved emulsion gel structure with higher gel elasticity, strength, water-holding capacity, and oxidative stability. This improvement could be attributed to the moderation of MP-EGC cross-linking, which was homogeneously formed among the adsorbed and/or unadsorbed proteins. Thus, oil droplets adhered better to the gel matrix. However, EGC at 100 μmol g-1 coupled with STP led to the formation of excessive non-disulfide covalent bonds, which aggravated the aggregation of MP. This ultimately reduced the protein digestibility and the nutritional value, caused the coalescence of oil droplets as well as the collapse of the gel structure, and thus, an overall decrease in the gel properties and oxidative stability. These results indicated that the enhanced oxidative stability and gelling capacity of MP without nutrition deterioration can be attained through tripolyphosphate coupled with lower doses of EGC.

The effect of binding of flavonoids, (-)-epigallocatechin-3-gallate (EGCG) and green tea extract (GTE), to beta-lactoglobulin (β-Lg) and micellar casein (micellar casein isolate, MCI) on protein digestibility was investigated. β-Lg resisted digestion by pepsin, but in the presence of EGCG the digestion of β-Lg was enhanced. Binding of EGCG to β-Lg was identified by nitro blue tetrazolium (NBT) staining and found, by isothermal titration calorimetry, to be an enthalpy-driven exothermic process, with a binding constant of 19 950 L mol -1 . Binding promoted a more rapid digestion of β-Lg during simulated upper duodenal digestion. NBT staining indicated a loss of binding of EGCG to β-Lg during combined gastric and distal small intestinal digestion and correlated with the cleavage of β-Lg. However, increased β-Lg heteromer formation and reduced β-Lg monomer digestibility were observed for the β-Lg-GTE complex. MCI was more digestible than β-Lg during pepsin digestion, but reduced digestibility was observed for both MCI-EGCG and MCI-GTE complexes, with loss of binding during intestinal digestion. The free radical scavenging capacity (FRSC) of EGCG remained stable for the β-Lg-EGCG complex throughout the gastric and intestinal phases of digestion, but this was significantly lowered for the MCI-EGCG complex. These results indicated that polyphenols bind to milk proteins modulating the in vitro digestibility and FRSC of β-Lg and MCI as a result of the formation of complexes.

The inhibition mechanism of epicatechin gallate (ECG) on tyrosinase was investigated by multispectroscopic techniques combined with molecular docking and molecular dynamics simulation. The results demonstrated that ECG suppressed the activity of tyrosinase in a reversible mixed-inhibition with a half inhibitory concentration (IC50) of (1.13 ± 0.82) × 10-5 mol L-1. Binding of ECG to tyrosinase led to the formation of a complex with the binding constant (Ksv) of 4.03 × 104 L mol-1 at 298 K which was stabilized by hydrophobic forces. The complex formation induced the intrinsic fluorescence quenching and secondary structure change of tyrosinase. Molecular docking results showed that hydrophobic and hydrogen bonding forces played a dominant role in the binding of ECG to tyrosinase, affecting the binding affinity of l-dopa to tyrosinase, leading to a decrease in tyrosinase activity. Molecular dynamics analysis indicated that ECG led to the stretching of the basic framework structure of tyrosinase and slightly influenced the microenvironment of amino acid residues. The research might provide new perspectives on the inhibition mechanism of epicatechin gallate on tyrosinase and a theoretical basis for the prevention and treatment of pigmented skin diseases and anti-browning of catechin as a food supplement.

Advanced glycation end products (AGEs) and their important intermediate products (α-dicarbonyl compounds) that are generated by the Maillard reaction are closely related to diabetes. Our study first investigated the mechanisms of the anti-glycation effects of epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin gallate (EGCG) in an alcoholic environment. The results showed that catechins played an important role in the inhibition of AGE formation, and the effect of EC was the best. Their corresponding mechanisms included total antioxidant capacity (TAOC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability, trapping of methylglyoxal (MGO), protection of the protein structure, and inhibition of the activities of α-amylase, α-glucosidase, and β-glucosidase, which were consistent with the study of molecular docking. This study will offer a theoretical basis for the applications of different types of catechins to alcoholic beverages as natural AGE formation inhibitors.

The interaction and antioxidant capacity between epigallocatechin gallate (EGCG) and β-lactoglobulin (β-Lg) under thermal treatments at 25-121 °C were investigated in this study. Fluorescence spectroscopy analysis showed that EGCG complexed with β-Lg mainly via non-covalent interactions and the binding affinity of EGCG to β-Lg was enhanced with heat treatment. EGCG showed a strong binding affinity to β-Lg after 85 °C heat treatment was applied, with a K a of 30.69 (±0.87) × 10 5 M -1 (pH 6.8, 298 K). Circular dichroism (CD) results showed that heat treatment did not result in greatly affected changes in the β-Lg secondary structure induced by β-Lg-EGCG interactions. MALDI-TOF/TOF-MS analysis showed that β-Lg-EGCG covalent conjugates initially formed after heat was applied at 60 °C, and their proportions increased under heat treatment ranging from 85 to 121 °C. The amino group of a lysine residue was further confirmed as the covalent binding site of EGCG to β-Lg. The β-Lg-EGCG interaction showed little effect on the antioxidant capacity (ABTS and ferric reducing antioxidant power (FRAP) values) of EGCG after heat treatment at 25-60 °C, but did induce an obvious reduction at temperatures above 85 °C. This study will provide the foundation for the use of EGCG in processing dairy products (such as milk tea beverages) with desirable nutrition and physiological functions.

Theasinensin A (TSA) and theasinensin B (TSB), dimers of tea catechins produced during the processing of oolong tea and black tea, had superior inhibitory effects on α-glucosidase. However, the potential inhibitory mechanisms on α-glucosidase are still unclear. In the present study, TSA and TSB were chemically synthesized and purified, and their inhibitory effects on α-glucosidase and potential mechanisms were investigated. The results showed that TSA and TSB could inhibit the activity of α-glucosidase in a reversible and noncompetitive manner with IC50 values of 6.342 and 24.464 μg mL-1, respectively, which were much lower than that of acarbose. The fluorescence and circular dichroism spectra revealed that TSA and TSB could alter the microenvironment and the secondary structure of α-glucosidase, thereby decreasing the α-glucosidase activity. Molecular docking results indicated that both TSA and TSB had a strong binding affinity to α-glucosidase by hydrophobic interactions and hydrogen bonds. Moreover, the stronger inhibition of TSA on α-glucosidase might be related to the closer binding site to the active site pocket of α-glucosidase.

It has been shown that supplementation of layers' diets with epigallocatechin-3-gallate (EGCG) can improve egg albumen quality, but the underlying mechanisms behind this response are unclear. In this study, we investigate the effect of EGCG on egg antioxidative activity, free amino acid and fatty acid profiles, and the underlying relationship between the EGCG and oxidant-sensitive mitogen-activated protein kinase (MAPK) signaling pathway in laying hens. 288 hens (35-weeks-old) were fed 0 and 165 mg kg-1 of EGCG diets over 8 weeks. EGCG led to an increase in the albumen height, Haugh unit, and activity of glutathione S-transferase (GST) and a reduction in MDA content in plasma (P < 0.05). Egg white tryptophan and yolk carotenoid content was also increased by EGCG (P < 0.05). Eggs from EGCG fed layers had higher total antioxidant capacity (T-AOC), reducing power (RP), and oxygen radical absorbance capacity (ORAC), and lower albumen and yolk MDA content (P < 0.05). Also, liver gene and protein expression of P-38MAPK, nuclear factor erythroid 2-related 2 (Nrf2) and hemeoxygenase 1 (HO-1) was up-regulated by EGCG. Our findings suggest that dietary EGCG increased the antioxidant activity of eggs and regulated the MAPK/Nrf2 signaling pathway.

Evidence has proven that the gut microbiota is an important environmental factor contributing to obesity by altering host energy harvest and storage. We performed a high-throughput 16S rDNA sequencing association study and serum metabolomics profiling in rats with a high-sugar diet. Our studies revealed that the high sugar diet reduced the diversity of cecal microorganisms, while the combination of theabrownin and the high sugar diet increased the diversity of cecal microorganisms and promoted reproduction of Alloprevotella, Coprostanoligenes&#95;group, Bacteroides, Prevotellaceae&#95;NK3B31&#95;group, Desulfovibrio, Intestinimonas, Alistipes, Bifidobacterium, Phascolarctobacterium, Ruminococcaceae&#95;UCG-010 and Staphylococcus. The combination also inhibited the growth of Lactobacillus, Prevotellaceae&#95;Ga6A1&#95;group and Tyzzerella. The Firmicutes/Bacteroidetes (F/B) ratio can be significantly reduced after the intervention of theabrownin in high sugar diet rats, and the reproduction of Bacteroides acidifaciens (BA) and Staphylococcus saprophyticus subsp. saprophyticus can be promoted. We found that the obesity-associated gut microbial species were linked to the changes in circulating metabolites. Serum levels of deoxycholic acid, cholic acid, 1H-indole-3-acetic acid, 3-indole acrylic acid and melatonin were negatively correlated with BA and Staphylococcus saprophyticus subsp. saprophyticus, but positively correlated with Lactobacillus murinus, Leptum and Gut&#95;metagenome. 2-Hydroxy-6-methylpyridin-3-carboxylic acid, l-homoserine, and 1,7-dimethylxanthine were positively correlated with BA and Staphylococcus saprophyticus subsp. saprophyticus, but negatively correlated with Lactobacillus murinus, Leptum, and Gut&#95;metagenome. In a high sugar diet mode, theabrownin reduced the body weight and triglycerides and improved insulin resistance mainly by targeting the reproduction of intestinal microorganisms such as BA, Staphylococcus saprophyticus subsp. saprophyticus, Lactobacillus murinus, Leptum, Gut&#95;metagenome and so on. A strong correlation between cecal microorganisms and serum metabolites, obesity and insulin resistance was observed. Theabrownin has high potential in reducing the risk of cardiovascular diseases such as diabetes and obesity.

A glycated whey protein isolate-epigallocatechin gallate (EGCG) nanocomplex-stabilized emulsion was used to encapsulate β-carotene. This study evaluated the stability of the emulsion in different environments and assessed its protective effect on β-carotene. The active compound-loaded emulsion was subjected to in vitro simulated digestion. The results show that the glycated whey protein isolate-EGCG nanocomplex-stabilized emulsion has greater storage, salt ion, and thermal stability than the whey protein isolate-EGCG nanocomplex. Moreover, the emulsion exerts a considerable inhibitory effect on the degradation of the active compounds. However, the strong hydrolysis of the protein by pancreatin prevents the emulsion from surviving in the intestinal fluid, and the speed and degree of lipolysis is faster and more intense than that of naked medium-chain triglyceride (MCT). This study provides useful information for the application of natural hydrophobic active ingredients to water-soluble edible protein emulsion systems in food and drug delivery.

The oxidation of unsaturated fats generally occurs at the oil-water interface of emulsions, so surface-active antioxidants are needed for inhibiting lipid oxidation. In this study, a scallop gonad protein isolate (SGPI)-epigallocatechin gallate (EGCG) conjugate was fabricated and characterized as an amphiphilic surface-active antioxidant in improving the physicochemical and oxidative stability of tuna oil-loaded emulsions via a free-radical grafting method. The covalent binding of EGCG to SGPIs was verified by using electrophoresis and gel permeation chromatography. Meanwhile, the structural, physical, thermal, as well as the in vitro antioxidant properties of the SGPI-EGCG conjugate were further characterized. The results indicated that the SGPI-EGCG conjugate contained more β-sheet but less α-helix than SGPIs, leading to the changes of the secondary and tertiary conformation stability after conjugation. The radical scavenging and oxygen radical absorbance capacity of SGPIs were significantly increased by 4.9 times and 7.4 times, respectively, after the EGCG-grafting reaction. Compared with that stabilized by SGPIs, tuna oil emulsions emulsified by the SGPI-EGCG conjugate exhibited a smaller particle size and better storage stability. Furthermore, the SGPI-EGCG conjugate inhibited lipid and fatty acid oxidation during storage more significantly in tuna oil emulsions than SGPIs due to its higher interfacial accumulation and antioxidant activities. These results suggested that the SGPI-EGCG conjugate could be utilized as an efficient surface-active antioxidant and emulsifier for the encapsulation and protection of unsaturated lipids.

Mucosal α-glucosidases from rat intestinal powder were employed, with a step to remove α-amylase, to measure the possibility of different inhibition of catechins, particularly those found in tea, on the four α-glucosidase enzymes. Inhibition of catechins was investigated for the slowing of digestion of glycemic carbohydrates, thus regulating glucose release and absorption. The α-glucosidases were fractionated using size-exclusion chromatography. The partially purified fractions showed higher α-glucosidase activity without any α-amylase activity. Catechins had selective inhibition properties on the α-glucosidases. In particular, (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) showed comparably high inhibitory effect on all four individual α-glucosidases, while (-)-epicatechin (EC), and (+)-catechin (C) indicated a more discriminating effect with relatively higher inhibitory effects on sucrase-isomaltase. The findings suggest that catechins differently inhibit the individual subunits of the α-glucosidases, and that they could modulate postprandial blood glucose levels through slowing digestion rate of starch and other glycemic carbohydrates, including sucrose.

(-)-Epigallocatechin-3-gallate (EGCG), a major phenolic constituent of tea, has been shown to have biological activity within inflammatory pathways involved with food allergies and intolerances. Proposed mechanisms for this effect include sequestration and structural modification of immunostimulatory proteins as a result of interactions with EGCG. The present study employs biophysical techniques including dynamic light scattering, circular dichroism and nuclear magnetic resonance to elucidate the likely mechanism(s) by which EGCG interacts with α2-gliadin (57-89) (α2g), an immunodominant peptide in celiac disease pathogenesis. We demonstrate that EGCG interacts with α2g in a multi-phase reaction driven by non-specific binding, resulting in the formation of polydisperse EGCG/α2g complexes which induce changes in peptide structure. We also show that these interactions occur at a range of pH levels associated with digestion, including pH 2.0, 6.8 and 7.5. Based on previous reports of binding specificity of enzymes and antigen presenting cells in celiac disease pathogenesis, our results provide foundational support for EGCG to prevent recognition of immunostimulatory gliadin epitopes by the body and thus prevent the inflammatory and autoimmune response associated with celiac disease.

Proteins, polysaccharides, and polyphenols can be assembled into ternary complexes with functional attributes that combine the desirable facets of each individual component. In the present work, we characterized the interactions among lactoferrin (LF), hyaluronic acid (HA) and (-)-epigallocatechin gallate (EGCG) dispersed in aqueous solutions at various pH values (2 to 9), HA levels (0 to 0.5 wt%), and EGCG levels (0 to 0.105 wt%). The antioxidant activity of the complexes was also evaluated. The ternary complexes formed macroscopic hydrogels at pH 2, microgel dispersions at pH 3, and soluble complexes at pH > 4. Information about the role of hydrogen bonds, electrostatic forces, and hydrophobic interactions was obtained using spectroscopic methods. The antioxidant activity of the ternary complexes was much higher at pH 5 than at pH 3, which was attributed to the ability of the hydrogels to inhibit the access of the free radicals generated in the aqueous phase to EGCG trapped inside. These results may be useful for optimizing the formulation of effective delivery systems for natural antioxidants.

(-)-Epigallocatechin-3-gallate (EGCG), the main bioactive component of tea catechins, exhibits broad-spectrum health efficacy against mitochondrial damage after subarachnoid hemorrhage (SAH). The mechanisms, however, are largely unknown. Here, the ability of EGCG to rescue mitochondrial dysfunction and mitochondrial dynamics following the inhibition of cell death was investigated by using in vitro and in vivo SAH models. EGCG blocked the cytosolic channel ([Ca2+])i influx via voltage-gated calcium channels (VGCCs), which induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization and reactive oxygen species (ROS) release. As expected, EGCG ameliorated oxyhemoglobin (OxyHb)-induced impairment of mitochondrial dynamics by regulating the expression of Drp1, Fis1, OPA1, Mfn1, and Mfn2. As a result, EGCG restored the increases in fragmented mitochondria and the mtDNA copy number in the OxyHb group to almost the normal level after SAH. In addition, the normal autophagic flux induced by EGCG at both the initiation and formation stages regulated Atg5 and Beclin-1 after SAH for the timely elimination of damaged mitochondria. In the end, EGCG increased the neurological score by decreasing cell death through the cyt c-mediated intrinsic apoptotic pathway. The results revealed the mechanisms behind the neuroprotective effects of EGCG via inhibition of the overloaded [Ca2+]i-induced mitochondrial dysfunction and the imbalanced mitochondrial fusion and fission cycle. Therefore, the simultaneous inhibition and timely elimination of damaged mitochondria could determine the therapeutic effect of EGCG.

Oleosomes, which are pre-emulsified oil bodies found naturally in plants, have excellent stability, therefore making their use more popular in the food industries. However, the mechanism of EGCG in regulating the physicochemical and oxidative stability, and digestion of oleosome emulsions is not yet clear. In this study, the effect of EGCG on the properties of soybean oleosome emulsions (SOE) was examined at different pH values (5.0, 7.0, and 9.0). EGCG was significantly more effective in maintaining the stability of SOE at pH 5.0 and 7.0 over the 14 days of storage, but less effective at pH 9.0. Furthermore, lipid oxidation of SOE at pH 7.0 was successfully retarded by incorporating EGCG, but not at pH 5.0 and 9.0. The in vitro gastrointestinal results suggested that EGCG retarded the digestion rate of SOE based on a 20% reduction in free fatty acid release. The results of this study will help food technologists to design slow-digestive oleosome-based products that will satisfy health-conscious consumers' demand for healthier food choices.

Numerous studies propose that epigallocatechin-3-gallate (EGCG), an abundant polyphenol in green tea, has anti-cancer properties. However, its mechanism of action in breast cancer remains unclear. This study investigated the capacity of EGCG to suppress breast cancer cell growth in vitro and in vivo, characterizing the underlying mechanisms, focusing on the effect of EGCG on glucose metabolism. EGCG reduced breast cancer 4T1 cell growth in a concentration- (10-320 μM) and time- (12-48 h) dependent manner. EGCG induced breast cancer apoptotic cell death at 24 h, as evidenced by annexin V/PI, caspase 3, caspase 8 and caspase 9 activation. Furthermore, EGCG affected the expression of 16 apoptosis-related genes, and promoted mitochondrial depolarization. EGCG induced autophagy concentration-dependently in 4T1 cells by modulating the levels of the autophagy-related proteins Beclin1, ATG5 and LC3B. Moreover, EGCG affected glucose, lactate and ATP levels. Mechanistically, EGCG significantly inhibited the activities and mRNA levels of the glycolytic enzymes hexokinase (HK), phosphofructokinase (PFK), and lactic dehydrogenase (LDH), and to a lesser extent the activity of pyruvate kinase (PK). In addition, EGCG decreased the expression of hypoxia-inducible factor 1α (HIF1α) and glucose transporter 1 (GLUT1), critical players in regulating glycolysis. In vivo, EGCG reduced breast tumor weight in a dose-dependent manner, reduced glucose and lactic acid levels and reduced the expression of the vascular endothelial growth factor (VEGF). In conclusion, EGCG exerts an anti-tumor effect through the inhibition of key enzymes that participate in the glycolytic pathway and the suppression of glucose metabolism.

As a major component of green tea, (-)-epigallocatechin-3-gallate (EGCG) has attracted interest from scientists owing to its potential to combat a variety of human diseases including abnormal glucose metabolism in obesity and diabetes. This study aims to (1) evaluate the molecular mechanism of EGCG in starch digestion before EGCG absorption; (2) investigate the link between PXR/CAR-mediated phase II metabolism and glucose homeostasis after EGCG is transported to small intestine and liver. EGCG suppressed starch hydrolysis both in vitro and in vivo. Molecular simulation results demonstrated that EGCG could bind to the active site of α-amylase and α-glucosidase, acting as an inhibitor. In addition, the anti-diabetic action of EGCG was investigated in high fat diet and STZ-induced type 2 diabetes. EGCG improved glucose homeostasis and inhibited the process of gluconeogenesis (PEPCK and G-6-Pase) and lipogenesis (SREBP-1C, FAS and ACC1) in the liver. Meanwhile, EGCG treatment activated PXR/CAR, accompanied by upgrading PXR/CAR-mediated phase II drug metabolism enzyme expression in small intestine and liver, involving SULT1A1, UGT1A1 and SULT2B1b. Dietary polyphenol EGCG could serve as a promising PXR/CAR activator and therapeutic intervention in diabetes.

Tea polyphenols (TP) have many health benefits, but most are metabolized into low molecular-weight phenolic acids after oral administration. In the present study, the absorption, metabolism, and excretion of catechins in rats fed a normal chow diet and in obese rats fed a high-fat and high-sugar (HFHS) diet were compared. After a ten-day oral administration of TP (500 mg per kg bw), the plasma levels of (-)-epigallocatechin gallate (EGCG) and (-)-gallocatechin gallate (GCG) in obese rats were significantly lower than those in the normal group. In obese rats, the fecal levels of EGCG, (-)-epicatechin gallate (ECG) and GCG were significantly enhanced. Ten phenolic metabolites of TP were quantitatively analyzed, and the results showed that 4-hydroxyphenylacetic acid was the primary metabolite in feces and plasma. The plasma and fecal concentrations of 4-hydroxyphenylacetic acid in the obese group were significantly lower than those in normal rats, but the levels of 4-hydroxyphenylpropionic acid in plasma and feces were increased. The content of other phenolic acids was also dramatically changed. These results suggested that a HFHS diet might influence the excretion of tea catechins, leading to insufficient metabolism of catechins by the gut microflora.

Our previous report demonstrated that epigallocatechin gallate (EGCg) promotes translocation of glucose transporter 4 (GLUT4) in skeletal muscle. In this study, we investigated the molecular mechanism of GLUT4 translocation by EGCg at the physiological concentration range. In L6 cells, EGCg induced phosphorylation of phosphatidylinositide 3'-kinase (PI3K) and downstream protein kinase C (PKC) λ/ξ without affecting the phosphorylation of insulin receptor and Akt. EGCg-induced GLUT4 translocation was suppressed by RNA interference-mediated knockdown of PI3K and treatment with PKC inhibitor Go6983. Moreover, EGCg increased Rac1 activity and actin remodelling as downstream events of PKCλ/ξ. These results indicate that EGCg induced GLUT4 translocation through a PI3K-dependent pathway, but its mode of action differed from that of insulin. EGCg also induced GLUT4 translocation through a 5'-adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway. 67 kDa laminin receptor, which is a target molecule of EGCg, was not involved in EGCg-induced glucose uptake in L6 cells. The oral administration of EGCg suppressed postprandial hyperglycaemia accompanied by GLUT4 translocation through both PI3K- and AMPK-dependent pathways, and promoted glycogen accumulation in skeletal muscle of ICR mice. EGCg promotes GLUT4 translocation through both PI3K- and AMPK-dependent pathways and glycogen accumulation in skeletal muscle.

In the present study, small angle X-ray scattering (SAXS) is applied to investigate the interaction between caseinophosphopeptides (CPP), the major digested product of milk protein, and chitosan (CS) under simulated gastrointestinal (GI) pH conditions. The change in pH value from the gastric to small intestinal environment induces complexation between CPP and CS, which is mainly driven by electrostatic interactions. The fractal dimension (Df) value of the domains inside the CPP-CS complexes is greater than 3, indicating the formation of dense particles/aggregates at the nanoscale. The Df value generally increases with an increase in the CS/CPP mass ratio. As a representative of polyphenols, (-)-epigallocatechin gallate (EGCG) associates with CS and CPP, forming nanocomplexes with a spherical shape and average particle size of around 208 nm. The formed CS-EGCG-CPP nanocomplexes do not affect the antioxidant activity of EGCG in the in vitro assays. Moreover, in the cellular assay, the nanocomplexes protect the RAW264.7 cells against H2O2-induced oxidative injury. In addition, the nanocomplexes significantly inhibit the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), TNF-α, IL-1β and IL-6. Furthermore, they inhibit the expression of iNOS, phosphorylation and degradation of IκB, as well as the translocation of NF-κB p65; this indicates that the mechanism for their anti-inflammatory activity is via the mediation of the NF-κB signaling pathway.

The global rise in obesity and type 2 diabetes has precipitated the need for therapeutic intervention in the arsenal against adiposity. (-)-Epigallocatechin-3-gallate (EGCG), a major nutraceutical component of green tea, has been regarded as a nutraceutical that has powerful antioxidant and anti-obesity bioactivities. In the present study, we showed that EGCG alleviates intracellular lipid accumulation markedly, and the inhibitory effect was largely limited to the early stage of adipocyte differentiation. Consistently, EGCG notably evoked the phosphorylation of AMPK and ACC and blunted the key enzymes of de novo lipogenesis. Interestingly, EGCG elicited iWAT-preadipocyte-derived mature white adipocyte beiging via activating thermogenic gene Ucp1 expression and mitochondrial biogenesis. Furthermore, our results also revealed that EGCG attenuated insulin signaling pathway blockage induced by TNF-α through the abrogation of redox imbalance and mitochondrial dysfunction. These findings indicate that EGCG is capable of suppressing adipogenesis and evoking white adipocyte beiging and therefore it may potentially serve as a novel approach to combat obesity.