Neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) against peripheral nerve transection-induced apoptosis.

PubMed

Kian, Kosar; Khalatbary, Ali Reza; Ahmadvand, Hassan; Karimpour Malekshah, Abbasali; Shams, Zahra

2018-01-02

Recent studies revealed the neuroprotective effects of epigallocatechin-3-gallate (EGCG) on a variety of neural injury models. The purpose of this study was to determine the neuroprotective effects of EGCG following sciatic nerve transection (SNT). Rats were randomly divided into four groups each as follows: Sham-operated group, SNT group, and Pre-EGCG (50-mg/kg, i.p., 30 minutes before nerve transection and followed for 3 days) and Post-EGCG (50-mg/kg, i.p., 1 hour after nerve transection and followed for 3 days) groups. Spinal cord segments of the sciatic nerve and related dorsal root ganglions were removed four weeks after nerve transection for the assessment of malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activities, immunohistochemistry of caspase-3, cyclooxygenase-2 (COX-2), S100beta (S100B), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). MDA levels were significantly decreased, and SOD and CAT activities were significantly increased in EGCG-treated rats after nerve transection. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the EGCG-treated rats after nerve transection. Also, EGCG significantly increased S100B expression. We propose that EGCG may be effective in the protection of neuronal cells against retrograde apoptosis and may enhance neuronal survival time following nerve transection.

Tea-induced improvement of endothelial function in humans: No role for epigallocatechin gallate (EGCG).

PubMed

Lorenz, Mario; Rauhut, Franziska; Hofer, Christine; Gwosc, Stefanie; Müller, Eda; Praeger, Damaris; Zimmermann, Benno F; Wernecke, Klaus-Dieter; Baumann, Gert; Stangl, Karl; Stangl, Verena

2017-05-23

Consumption of tea is inversely associated with cardiovascular diseases. However, the active compound(s) responsible for the protective effects of tea are unknown. Although many favorable cardiovascular effects in vitro are mediated by epigallocatechin gallate (EGCG), its contribution to the beneficial effects of tea in vivo remains unresolved. In a randomised crossover study, a single dose of 200 mg EGCG was applied in three different formulas (as green tea beverage, green tea extract (GTE), and isolated EGCG) to 50 healthy men. Flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation (NMD) was measured before and two hours after ingestion. Plasma levels of tea compounds were determined after each intervention and correlated with FMD. FMD significantly improved after consumption of green tea containing 200 mg EGCG (p < 0.01). However, GTE and EGCG had no significant effect on FMD. NMD did not significantly differ between interventions. EGCG plasma levels were highest after administration of EGCG and lowest after consumption of green tea. Plasma levels of caffeine increased after green tea consumption. The results show that EGCG is most likely not involved in improvement of flow-mediated dilation by green tea. Instead, other tea compounds, metabolites or combinations thereof may play a role.

Evaluation of nanohydroxyapaptite (nano-HA) coated epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes.

PubMed

Chu, Chenyu; Deng, Jia; Man, Yi; Qu, Yili

2017-09-01

Collagen is the main component of extracellular matrix (ECM) with desirable biological activities and low antigenicity. Collagen materials have been widely utilized in guided bone regeneration (GBR) surgery due to its abilities to maintain space for hard tissue growth. However, pure collagen lacks optimal mechanical properties. In our previous study, epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes, with better biological activities and enhanced mechanical properties, may promote osteoblast proliferation, but their effect on osteoblast differentiation is not very significant. Nanohydroxyapatite (nano-HA) is the main component of mineral bone, which possesses exceptional bioactivity properties including good biocompatibility, high osteoconductivity and osteoinductivity, non-immunogenicity and non-inflammatory behavior. Herein, by analyzing the physical and chemical properties as well as the effects on promoting bone regeneration, we have attempted to present a novel EGCG-modified collagen membrane with nano-HA coating, and have found evidence that the novel collagen membrane may promote bone regeneration with a better surface morphology, without destroying collagen backbone. To evaluate the surface morphologies, chemical and mechanical properties of pure collagen membranes, epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes, nano-HA coated collagen membranes, nano-HA coated EGCG-collagen membranes, (ii) to evaluate the bone regeneration promoted by theses membranes. In the present study, collagen membranes were divided into 4 groups: (1) untreated collagen membranes (2) EGCG cross-linked collagen membranes (3) nano-HA modified collagen membranes (4) nano-HA modified EGCG-collagen membranes. Scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to evaluate surface morphologies and chemical properties, respectively. Mechanical properties were determined by differential scanning calorimeter (DSC

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy.

PubMed

Lecumberri, Elena; Dupertuis, Yves Marc; Miralbell, Raymond; Pichard, Claude

2013-12-01

Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea

PubMed Central

Steinmann, J; Buer, J; Pietschmann, T; Steinmann, E

2013-01-01

The consumption of green tea (Camellia sinensis) has been shown to have many physiological and pharmacological health benefits. In the past two decades several studies have reported that epigallocatechin-3-gallate (EGCG), the main constituent of green tea, has anti-infective properties. Antiviral activities of EGCG with different modes of action have been demonstrated on diverse families of viruses, such as Retroviridae, Orthomyxoviridae and Flaviviridae and include important human pathogens like human immunodeficiency virus, influenza A virus and the hepatitis C virus. Furthermore, the molecule interferes with the replication cycle of DNA viruses like hepatitis B virus, herpes simplex virus and adenovirus. Most of these studies demonstrated antiviral properties within physiological concentrations of EGCG in vitro. In contrast, the minimum inhibitory concentrations against bacteria were 10–100-fold higher. Nevertheless, the antibacterial effects of EGCG alone and in combination with different antibiotics have been intensively analysed against a number of bacteria including multidrug-resistant strains such as methicillin-resistant Staphylococcus aureus or Stenotrophomonas maltophilia. Furthermore, the catechin EGCG has antifungal activity against human-pathogenic yeasts like Candida albicans. Although the mechanistic effects of EGCG are not fully understood, there are results indicating that EGCG binds to lipid membranes and affects the folic acid metabolism of bacteria and fungi by inhibiting the cytoplasmic enzyme dihydrofolate reductase. This review summarizes the current knowledge and future perspectives on the antibacterial, antifungal and antiviral effects of the green tea constituent EGCG. PMID:23072320

Structural Modification of (-)-Epigallocatechin Gallate (EGCG) Shows Significant Enhancement in Mitochondrial Biogenesis.

PubMed

Ha, Taewoong; Kim, Mi Kyoung; Park, Kwang-Su; Jung, Woong; Choo, Hyunah; Chong, Youhoon

2018-04-18

(-)-Epigallocatechin-3-gallate (EGCG) is known as a mitochondria-targeted molecule that can prevent mitochondrial deterioration and induce mitochondrial biogenesis by modulating key regulators of mitochondrial metabolism. In this study, we tackled whether derivatization of EGCG could result in enhancement of its effects on mitochondrial biogenesis. EGCG, EGCG peracetate (AcEGCG), and its 4″- O-alkyl substituted congeners prepared by previously reported procedures were biologically evaluated. Interestingly, EGCG and AcEGCG were only marginally effective in inducing mitochondrial biogenesis, while AcEGCG congeners with an alkyl group at the 4″- O position showed significantly increased biological activity compared to their parent compound. Among these series, 3f with a methyl-branched carbonate chain at the 4″- O position of the AcEGCG scaffold showed the most enhancement in inducing mitochondrial biogenesis. Hepa1-6 cells treated with 3f exhibited increases in both mitochondrial mass (1.5 times) and relative mtDNA content to nDNA (1.5 times). As a mitochondrial biogenesis enhancer, 3f also increased expression levels of regulators for mitochondrial function, including PGC-1α (4.0 fold), p-AMPK (2.5 fold), SIRT1 (4.2 fold), ERRα (1.8 fold), NRF-1 (1.6 fold), NRF-2 (1.7 fold), and mtTFA (1.6 folds). Investigation of oxidative phosphorylation by mitochondria in the presence of 3f revealed that 3f increased the NAD + /NADH ratio, the amount of cytochrome c, ATP synthesis, and oxygen consumption in Hepa1-6 cells by 2.2, 1.4, 1.5, and 2.1 fold, respectively. Taken together, these results warrant an extensive structure-activity relationship study for EGCG derivatives to develop novel mitochondrial biogenesis enhancers.

Antifibrotic properties of epigallocatechin-3-gallate in endometriosis.

PubMed

Matsuzaki, Sachiko; Darcha, Claude

2014-08-01

Is epigallocatechin-3-gallate (EGCG) treatment effective in the treatment of fibrosis in endometriosis? EGCG appears to have antifibrotic properties in endometriosis. Histologically, endometriosis is characterized by dense fibrous tissue surrounding the endometrial glands and stroma. However, only a few studies to date have evaluated candidate new therapies for endometriosis-associated fibrosis. For this laboratory study, samples from 55 patients (45 with and 10 without endometriosis) of reproductive age with normal menstrual cycles were analyzed. A total of 40 nude mice received single injection proliferative endometrial fragments from a total of 10 samples. The in vitro effects of EGCG and N-acetyl-l-cysteine on fibrotic markers (alpha-smooth muscle actin, type I collagen, connective tissue growth factor and fibronectin) with and without transforming growth factor (TGF)-β1 stimulation, as well as on cell proliferation, migration and invasion and collagen gel contraction of endometrial and endometriotic stromal cells were evaluated by real-time PCR, immunocytochemistry, cell proliferation assays, in vitro migration and invasion assays and/or collagen gel contraction assays. The in vitro effects of EGCG on mitogen-activated protein kinase (MAPK) and Smad signaling pathways in endometrial and endometriotic stromal cells were evaluated by western blotting. Additionally, the effects of EGCG treatment on endometriotic implants were evaluated in a xenograft model of endometriosis in immunodeficient nude mice. Treatment with EGCG significantly inhibited cell proliferation, migration and invasion of endometrial and endometriotic stromal cells from patients with endometriosis. In addition, EGCG treatment significantly decreased the TGF-β1-dependent increase in the mRNA expression of fibrotic markers in both endometriotic and endometrial stromal cells. Both endometriotic and endometrial stromal cell-mediated contraction of collagen gels were significantly attenuated at 8

Wnt/β-catenin pathway mediates (-)-Epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells.

PubMed

Zhu, Jianyun; Jiang, Ye; Yang, Xue; Wang, Shijia; Xie, Chunfeng; Li, Xiaoting; Li, Yuan; Chen, Yue; Wang, Xiaoqian; Meng, Yu; Zhu, Mingming; Wu, Rui; Huang, Cong; Ma, Xiao; Geng, Shanshan; Wu, Jieshu; Zhong, Caiyun

2017-01-01

Cancer stem cells (CSCs) play essential role in the progression of many tumors. Wnt/β-catenin pathway is crucial in maintaining the stemness of CSCs. (-)-Epigallocatechin-3-gallate (EGCG), the major bioactive component in green tea, has been shown to possess anti-cancer activity. To date, the interventional effect of EGCG on lung CSCs has not been elucidated yet. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We revealed that Wnt/β-catenin pathway was activated in lung CSCs, and downregulation of β-catenin, abolished lung CSCs traits. Our study further illustrated that EGCG effectively diminished lung CSCs activity by inhibiting tumorsphere formation, decreasing lung CSCs markers, suppressing proliferation and inducing apoptosis. Moreover, We showed that EGCG downregulated Wnt/β-catenin activation, while upregulation of Wnt/β-catenin dampened the inhibitory effects of EGCG on lung CSCs. Taken together, these results demonstrated the role of Wnt/β-catenin pathway in regulating lung CSCs traits and EGCG intervention of lung CSCs. Findings from this study could provide new insights into the molecular mechanisms of lung CSCs intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Computational and Biochemical Discovery of RSK2 as a Novel Target for Epigallocatechin Gallate (EGCG).

PubMed

Chen, Hanyong; Yao, Ke; Chang, Xiaoyu; Shim, Jung-Hyun; Kim, Hong-Gyum; Malakhova, Margarita; Kim, Dong-Joon; Bode, Ann M; Dong, Zigang

2015-01-01

The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). Protein interaction with EGCG is a critical step for mediating the effects of EGCG on the regulation of various key molecules involved in signal transduction. By using computational docking screening methods for protein identification, we identified a serine/threonine kinase, 90-kDa ribosomal S6 kinase (RSK2), as a novel molecular target of EGCG. RSK2 includes two kinase catalytic domains in the N-terminal (NTD) and the C-terminal (CTD) and RSK2 full activation requires phosphorylation of both terminals. The computer prediction was confirmed by an in vitro kinase assay in which EGCG inhibited RSK2 activity in a dose-dependent manner. Pull-down assay results showed that EGCG could bind with RSK2 at both kinase catalytic domains in vitro and ex vivo. Furthermore, results of an ATP competition assay and a computer-docking model showed that EGCG binds with RSK2 in an ATP-dependent manner. In RSK2+/+ and RSK2-/- murine embryonic fibroblasts, EGCG decreased viability only in the presence of RSK2. EGCG also suppressed epidermal growth factor-induced neoplastic cell transformation by inhibiting phosphorylation of histone H3 at Ser10. Overall, these results indicate that RSK2 is a novel molecular target of EGCG.

Epigallocatechin gallate incorporation into lignin enhances the alkaline delignification and enzymatic saccharification of cell walls

USDA-ARS?s Scientific Manuscript database

Epigallocatechin gallate (EGCG) was evaluated as a potential lignin bioengineering target for rendering biomass more amenable to processing for biofuel production. In vitro peroxidase-catalyzed polymerization experiments revealed that both gallate and pyrogalloyl (B-ring) moieties in EGCG underwent ...

Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review.

PubMed

Gan, Ren-You; Li, Hua-Bin; Sui, Zhong-Quan; Corke, Harold

2018-04-13

Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.

Crystal Engineering of Green Tea Epigallocatechin-3-gallate (EGCg) Cocrystals and Pharmacokinetic Modulation in Rats

PubMed Central

2013-01-01

The most abundant polyphenol in green tea, epigallocatechin-3-gallate (EGCg), has recently received considerable attention due to the discovery of numerous health-promoting bioactivities. Despite reports of its poor oral bioavailability, EGCg has been included in many dietary supplement formulations. Conventional preformulation methods have been employed to improve the bioavailability of EGCg. However, these methods have limitations that hinder the development of EGCg as an effective therapeutic agent. In this study, we have utilized the basic concepts of crystal engineering and several crystallization techniques to screen for various solid crystalline forms of EGCg and evaluated the efficacy of crystal engineering for modulating the pharmacokinetics of EGCg. We synthesized and characterized seven previously undescribed crystal forms of EGCg including the pure crystal structure of EGCg. The aqueous solubility profiles of four new EGCg cocrystals were determined. These cocrystals were subsequently dosed at 100 mg EGCg per kg body weight in rats, and the plasma levels were monitored over the course of eight hours following the single oral dose. Two of the EGCg cocrystals were found to exhibit modest improvements in relative bioavailability. Further, cocrystallization resulted in marked effects on pharmacokinetic parameters including Cmax, Tmax, area under curve, relative bioavailability, and apparent terminal half-life. Our findings suggest that modulation of the pharmacokinetic profile of EGCg is possible using cocrystallization and that it offers certain opportunities that could be useful during its development as a therapeutic agent. PMID:23730870

Protonation of epigallocatechin-3-gallate (EGCG) results in massive aggregation and reduced oral bioavailability of EGCG-dispersed selenium nanoparticles.

PubMed

Wu, Shanshan; Sun, Kang; Wang, Xin; Wang, Dongxu; Wan, Xiaochun; Zhang, Jinsong

2013-07-31

The current results show that epigallocatechin-3-gallate (EGCG), in the form of phenolic anions at pH 8.0, can effectively disperse selenium nanoparticles. However, at gastric juice pH (1.0), the EGCG-dispersed selenium nanoparticles (referred to as E-Se) extensively aggregated, so that nano features largely disappeared. This demonstrates that deprotonated phenolic anions of EGCG play an important role in maintaining E-Se stability and suggests that E-Se would suffer from reduced oral bioavailability. To validate this conjecture, size-equivalent E-Se and bovine serum albumin (BSA)-dispersed selenium nanoparticles (B-Se), whose physicochemical properties were not altered at pH 1.0, were orally administered to selenium-deficient mice. In comparison to B-Se, the bioavailabilities of E-Se as indicated with hepatic and renal glutathione peroxidase activity and hepatic selenium levels were significantly (p < 0.01) reduced by 39, 32, and 31%, respectively. Therefore, the present study reveals that size-equivalent selenium nanoparticles prepared by different dispersers do not necessarily guarantee equivalent oral bioavailability.

Potential Role of (-)-Epigallocatechin-3-Gallate (EGCG) in the Secondary Prevention of Alzheimer Disease.

PubMed

Xicota, Laura; Rodriguez-Morato, Jose; Dierssen, Mara; de la Torre, Rafael

2017-01-01

Medical advances in the last decades have increased the average life expectancy, but also the incidence and prevalence of age-associated neurodegenerative diseases. Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and the most prevalent type of dementia. A plethora of different mechanisms contribute to AD, among which oxidative stress plays a key role in its development and progression. So far, there are no pharmacological treatments available and the current medications are mainly symptomatic. In the last years, dietary polyphenols have gained research attention due to their interesting biological activities, and more specifically their antioxidant properties. (-)- Epigallocatechin-3-gallate (EGCG) is a natural flavanol that has been extensively studied regarding its potential effects in AD. In this review we present the current in vitro and in vivo experimentation regarding the use of EGCG in AD. We also review the complex mechanisms of action of EGCG, not only limited to its antioxidant activity, which may explain its beneficial health effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

(-)-Epigallocatechin-3-O-gallate (EGCG) attenuates the hemodynamics stimulated by caffeine through decrease of catecholamines release.

PubMed

Han, Jin-Yi; Moon, Yong-Jin; Han, Jong-Hyun; Kim, Jong-Hoon; Woo, Jae-Hoon; Yoo, Hwan-Soo; Hong, Jin Tae; Ahn, Hee-Yul; Hong, Jong-Myeon; Oh, Ki-Wan

2016-09-01

A human study of the effects on hemodynamics of caffeine and epigallocatechin-3-O-gallate (EGCG) was performed. Caffeine tablets (200 mg) were orally administered to healthy males aged between 25 and 35 years 30 min after oral administration of EGCG tablets (100 and 200 mg). The increase in BP induced by caffeine was inhibited when co-administrated with EGCG. We found that caffeine slightly decreased heart rate (HR) in the volunteers. Although EGCG enhanced HR reduction, the effect was not significant. In addition, caffeine increased blood catecholamine levels, but EGCG inhibited the increase in noradrenaline, adrenaline and dopamine levels induced by caffeine. Whether EGCG decreases the elevated HR and systolic perfusion pressure, and ventricular contractility induced by adrenergic agonists in the isolated rat heart was investigated. The modified Krebs-Henseleit solution was perfused through a Langendorff apparatus to the isolated hearts of rats. HR, systolic perfusion pressure, and developed maximal rates of contraction (+dP/dtmax) and relaxation (-dP/dtmax) were increased by epinephrine (EP) and isoproterenol (IP). In contrast, EGCG decreased the elevated HR, systolic perfusion pressure, and left ventricular ±dp/dtmax induced by EP and/or IP. In conclusion, EGCG could attenuate the hemodynamics stimulated by caffeine through decreasing catecholamine release.

Formulation, characteristics and antiatherogenic bioactivities of CD36-targeted epigallocatechin gallate (EGCG)-loaded nanoparticles.

PubMed

Zhang, Jia; Nie, Shufang; Martinez-Zaguilan, Raul; Sennoune, Souad R; Wang, Shu

2016-04-01

Intimal macrophages are determinant cells for atherosclerotic lesion formation by releasing inflammatory factors and taking up oxidized low-density lipoprotein (oxLDL) via scavenger receptors, primarily the CD36 receptor. (-)-Epigallocatechin-3-gallate (EGCG) has a potential to decrease cholesterol accumulation and inflammatory responses in macrophages. We made EGCG-loaded nanoparticles (Enano) using phosphatidylcholine, kolliphor HS15, alpha-tocopherol acetate and EGCG. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), a CD36-targeted ligand found on oxLDL, was incorporated on the surface of Enano to make ligand-Enano (L-Enano). The objectives of this study are to deliver EGCG to macrophages via CD36-targeted L-Enano and to determine its antiatherogenic bioactivities. The optimized nanoparticles obtained in our study were spherical and around 108 nm in diameter, and had about 10% of EGCG loading capacity and 96% of EGCG encapsulation efficiency. Compared to Enano, CD36-targeted L-Enano had significantly higher binding affinity to and uptake by macrophages at the same pattern as oxLDL. CD36-targeted L-Enano dramatically improved EGCG stability, increased macrophage EGCG content, delivered EGCG to macrophage cytosol and avoided lysosomes. L-Enano significantly decreased macrophage mRNA levels and protein secretion of monocyte chemoattractant protein 1, but did not significantly change macrophage cholesterol content. The innovative CD36-targeted nanoparticles may facilitate targeted delivery of diagnostic, preventive and therapeutic compounds to intimal macrophages for the diagnosis, prevention and treatment of atherosclerosis with enhanced efficacy and decreased side effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Epigallocatechin Gallate (EGCG) Inhibits Alpha-Synuclein Aggregation: A Potential Agent for Parkinson's Disease.

PubMed

Xu, Yan; Zhang, Yanyan; Quan, Zhenzhen; Wong, Winnie; Guo, Jianping; Zhang, Rongkai; Yang, Qinghu; Dai, Rongji; McGeer, Patrick L; Qing, Hong

2016-10-01

Protein aggregation is a prominent feature of many neurodegenerative disorders including Parkinson's disease (PD). Aggregation of alpha-synuclein (SNCA) may underlie the pathology of PD. They are the main components of Lewy bodies and dystrophic neurites that are the intraneuronal inclusions characteristic of the disease. We have demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibited SNCA aggregation, which made it a candidate for therapeutic intervention in PD. Three methods were used: SNCA fibril formation inhibition by EGCG in incubates; inhibition of the SNCA fluorophore A-Syn-HiLyte488 binding to plated SNCA in microwells; and inhibition of the A-Syn-HiLyte488 probe binding to aggregated SNCA in postmortem PD tissue. Recombinant human SNCA was incubated under conditions that result in fibril formation. The aggregation was blocked by 100 nM EGCG in a concentration-dependent manner, as shown by an absence of thioflavin T binding. In the microplate assay system, the ED 50 of EGCG inhibition of A-Syn-HiLyte488 binding to coated SNCA was 250 nM. In the PD tissue based assay, SNCA aggregates were recognized by incubation with 7 nM of A-Syn-HiLyte488. This binding was blocked by EGCG in a concentration dependent manner. The SNCA amino acid sites, which potentially interacted with EGCG, were detected on peptide membranes. It was implicated that EGCG binds to SNCA by instable hydrophobic interactions. In this study, we suggested that EGCG could be a potent remodeling agent of SNCA aggregates and a potential disease modifying drug for the treatment of PD and other α-synucleinopathies.

Production of monodisperse epigallocatechin gallate (EGCG) microparticles by spray drying for high antioxidant activity retention.

PubMed

Fu, Nan; Zhou, Zihao; Jones, Tyson Byrne; Tan, Timothy T Y; Wu, Winston Duo; Lin, Sean Xuqi; Chen, Xiao Dong; Chan, Peggy P Y

2011-07-15

Epigallocatechin gallate (EGCG) originated from green tea is well-known for its pharmaceutical potential and antiproliferating effect on carcinoma cells. For drug delivery, EGCG in a micro-/nanoparticle form is desirable for their optimized chemopreventive effect. In this study, first time reports that EGCG microparticles produced by low temperature spray drying can maintain high antioxidant activity. A monodisperse droplet generation system was used to realize the production of EGCG microparticles. EGCG microparticles were obtained with narrow size distribution and diameter of 30.24 ± 1.88 μM and 43.39 ± 0.69 μM for pure EGCG and lactose-added EGCG, respectively. The EC50 value (the amount of EGCG necessary to scavenge 50% of free radical in the medium) of spray dried pure EGCG particles obtained from different temperature is in the range of 3.029-3.075 μM compared to untreated EGCG with EC50 value of 3.028 μM. Varying the drying temperatures from 70°C and 130°C showed little detrimental effect on EGCG antioxidant activity. NMR spectrum demonstrated the EGCG did not undergo chemical structural change after spray drying. The major protective mechanism was considered to be: (1) the use of low temperature and (2) the heat loss from water evaporation that kept the particle temperature at low level. With further drier optimization, this monodisperse spray drying technique can be used as an efficient and economic approach to produce EGCG micro-/nanoparticles. Published by Elsevier B.V.

Data in support of the negative influence of divalent cations on (−)-epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2)

PubMed Central

Deb, Gauri; Batra, Sahil; Limaye, Anil M.

2015-01-01

In this data article we have provided evidence for the negative influence of divalent cations on (−)‐epigallocatechin-3-gallate (EGCG)-mediated inhibition of matrix metalloproteinase-2 (MMP-2) activity in cell-free experiments. Chelating agents, such as EDTA and sodium citrate alone, did not affect MMP-2 activity. While EDTA enhanced, excess of divalent cations interfered with EGCG-mediated inhibition of MMP-2. PMID:26977427

PPARα activation sensitizes cancer cells to epigallocatechin-3-gallate (EGCG) treatment via suppressing heme oxygenase-1.

PubMed

Zhang, Shuyu; Yang, Xiaodong; Luo, Judong; Ge, Xin; Sun, Wanping; Zhu, Hong; Zhang, Weiping; Cao, Jianping; Hou, Yinglong

2014-01-01

Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant that may have potential therapeutic applications for the treatment of many disorders, including cancer. Peroxisome proliferator-activated receptor-α (PPARα) has been shown to play a key role in diverse metabolic and cellular functions. PPARα modulates target gene expression by binding to specific regions on the DNA of target genes. The effects and mechanisms of PPARα activation on EGCG efficacy have not yet been analyzed in cancer cells. We found that when cancer cells were exposed to EGCG, the expression of PPARα was increased at the protein level in a dose-dependent manner. The PPARα agonist clofibrate blocked cytoprotective heme oxygenase-1 (HO-1) induction and sensitized multiple types of cancer cells to EGCG-induced cell death. Conversely, the PPARα inhibitor G6471 and PPARα siRNA increased HO-1 expression. Electro-mobility shift assays (EMSA) and in vivo chromatin immunoprecipitation (ChIP) confirmed that PPARα interacts with the peroxisome proliferator-responsive element of the HO-1 promoter. Moreover, cell death induced by EGCG plus clofibrate was partially reversed by HO-1 overexpression in PANC1 cells. These results indicate that PPARα is a direct and negative regulator of HO-1 induced by EGCG and confers cell susceptibility to EGCG.

Wnt/β-catenin pathway mediates (−)-Epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Jianyun; Jiang, Ye; Yang, Xue

Cancer stem cells (CSCs) play essential role in the progression of many tumors. Wnt/β-catenin pathway is crucial in maintaining the stemness of CSCs. (−)-Epigallocatechin-3-gallate (EGCG), the major bioactive component in green tea, has been shown to possess anti-cancer activity. To date, the interventional effect of EGCG on lung CSCs has not been elucidated yet. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We revealed that Wnt/β-catenin pathway was activated in lung CSCs, and downregulation of β-catenin, abolished lung CSCs traits. Our study further illustrated that EGCG effectively diminished lung CSCs activitymore » by inhibiting tumorsphere formation, decreasing lung CSCs markers, suppressing proliferation and inducing apoptosis. Moreover, We showed that EGCG downregulated Wnt/β-catenin activation, while upregulation of Wnt/β-catenin dampened the inhibitory effects of EGCG on lung CSCs. Taken together, these results demonstrated the role of Wnt/β-catenin pathway in regulating lung CSCs traits and EGCG intervention of lung CSCs. Findings from this study could provide new insights into the molecular mechanisms of lung CSCs intervention. - Highlights: • EGCG inhibited lung CSCs activity. • EGCG inhibited lung CSCs activity via Wnt/β-catenin pathway suppression. • EGCG may prove to be a potential therapeutic agent for lung cancer.« less

Macrophage phenotype in the epigallocatechin-3-gallate (EGCG)-modified collagen determines foreign body reaction.

PubMed

Chu, Chenyu; Liu, Li; Wang, Yufei; Wei, Shimin; Wang, Yuanjing; Man, Yi; Qu, Yili

2018-04-28

Collagen has been widely used in guided bone regeneration, and the implantation of collagen membranes will elicit the foreign body reaction (FBR). The imbalance of FBR often leads to failure of dental implants. Therefore, modulation of the FBR after implantation of collagen membranes becomes increasingly important. Macrophages, pivotal in FBR, have been distinguished into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Epigallocatechin-3-gallate (EGCG)-modified collagen membranes have been previously shown to regulate secretion of inflammatory factors. In this study, immunohistochemistry of CD31 showed that areas of blood vessels were significantly enlarged after implantation of EGCG-modified collagen membranes compared with those treated with pure collagen membranes. Besides, haematoxylin-eosin staining and immunofluorescence showed an increased number of M2 macrophages after implantation of EGCG-modified collagen membranes. In addition, quantitative real-time polymerase chain reaction showed that after implantation of EGCG-modified collagen membranes, expression of CXCL1 (predominant chemoattractants to neutrophils and inflammation promotors) was significantly downregulated, whereas expressions of STAB1, CCR2, CCR3, CCL2, and CCL3 (related to M2 macrophages) were significantly upregulated. From these findings, we conclude that EGCG-modified collagen membranes were able to regulate the recruitment and polarization of macrophages, so that ameliorate FBR. Copyright © 2018 John Wiley & Sons, Ltd.

Immunomodulating effect of epigallocatechin-3-gallate from green tea: mechanisms and applications

USDA-ARS?s Scientific Manuscript database

Consuming green tea or its active ingredient, epigallocatechin 3-gallate (EGCG), has been shown consistently to benefit the healthy functioning of several body systems. In the immune system specifically, accumulating evidence has revealed an immunomodulating effect of green tea/EGCG. Several types ...

Epigallocatechin gallate (EGCG) attenuates infrasound-induced neuronal impairment by inhibiting microglia-mediated inflammation.

PubMed

Cai, Jing; Jing, Da; Shi, Ming; Liu, Yang; Lin, Tian; Xie, Zhen; Zhu, Yi; Zhao, Haibo; Shi, Xiaodan; Du, Fang; Zhao, Gang

2014-07-01

Infrasound, a kind of common environmental noise and a major contributor of vibroacoustic disease, can induce the central nervous system (CNS) damage. However, no relevant anti-infrasound drugs have been reported yet. Our recent studies have shown that infrasound resulted in excessive microglial activation rapidly and sequential inflammation, revealing a potential role of microglia in infrasound-induced CNS damage. Epigallocatechin gallate (EGCG), a major bioactive component in green tea, has the capacity of protecting against various neurodegenerative diseases via an anti-inflammatory mechanism. However, it is still unknown to date whether EGCG acts on infrasound-induced microglial activation and neuronal damage. We showed that, after 1-, 2- or 5-day exposure of rats to 16 Hz, 130 dB infrasound (2 h/day), EGCG significantly inhibited infrasound-induced microglial activation in rat hippocampal region, evidenced by reduced expressions of Iba-1 (a marker for microglia) and proinflammatory cytokines (IL-1β, IL-6, IL-18 and TNF-α). Moreover, infrasound-induced neuronal apoptosis in rat hippocampi was significantly suppressed by EGCG. EGCG also inhibited infrasound-induced activation of primary microglia in vitro and decreased the levels of proinflammatory cytokines in the supernatants of microglial culture, which were toxic to cultured neurons. Furthermore, EGCG attenuated infrasound-induced increases in nuclear NF-κB p65 and phosphorylated IκBα, and ameliorated infrasound-induced decrease in IκB in microglia. Therefore, our study provides the first evidence that EGCG acts against infrasound-induced neuronal impairment by inhibiting microglia-mediated inflammation through a potential NF-κB pathway-related mechanism, suggesting that EGCG can be used as a promising drug for the treatment of infrasound-induced CNS damage. Copyright © 2014 Elsevier Inc. All rights reserved.

Epigallocatechin-3-gallate and Epigallocatechin-3-O-(3-O-methyl)-gallate Enhance the Bonding Stability of an Etch-and-Rinse Adhesive to Dentin

PubMed Central

Yu, Hao-Han; Zhang, Ling; Yu, Fan; Li, Fang; Liu, Zheng-Ya; Chen, Ji-Hua

2017-01-01

This study evaluated epigallocatechin-3-gallate (EGCG) and epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG-3Me) modified etch-and-rinse adhesives (Single Bond 2, SB 2) for their antibacterial effect and bonding stability to dentin. EGCG-3Me was isolated and purified with column chromatography and preparative high performance liquid chromatography. EGCG and EGCG-3Me were incorporated separately into the adhesive SB 2 at concentrations of 200, 400, and 600 µg/mL. The effect of cured adhesives on the growth of Streptococcus mutans (S. mutans) was determined with scanning electron microscopy and confocal laser scanning microscopy; the biofilm of bacteria was further quantified via optical density 600 values. The inhibition of EGCG and EGCG-3Me on dentin-originated collagen proteases activities was evaluated with a proteases fluorometric assay kit. The degree of conversion (DC) of the adhesives was tested with micro-Raman spectrum. The immediate and post-thermocycling (5000 cycles) bond strength was assessed through Microtensile Bond Strength (MTBS) test. Cured EGCG/EGCG-3Me modified adhesives inhibit the growth of S. mutans in a concentration-dependent manner. The immediate MTBS of SB 2 was not compromised by EGCG/EGCG-3Me modification. EGCG/EGCG-3Me modified adhesive had higher MTBS than SB 2 after thermocycling, showing no correlation with concentration. The DC of the adhesive system was affected depending on the concentration of EGCG/EGCG-3Me and the depth of the hybrid layer. EGCG/EGCG-3Me modified adhesives could inhibit S. mutans adhesion to dentin–resin interface, and maintain the bonding stability. The adhesive modified with 400 µg/mL EGCG-3Me showed antibacterial effect and enhanced bonding stability without affect the DC of adhesive. PMID:28772546

Epigallocatechin-3-gallate and Epigallocatechin-3-O-(3-O-methyl)-gallate Enhance the Bonding Stability of an Etch-and-Rinse Adhesive to Dentin.

PubMed

Yu, Hao-Han; Zhang, Ling; Yu, Fan; Li, Fang; Liu, Zheng-Ya; Chen, Ji-Hua

2017-02-15

This study evaluated epigallocatechin-3-gallate (EGCG) and epigallocatechin-3- O -(3- O -methyl)-gallate (EGCG-3Me) modified etch-and-rinse adhesives (Single Bond 2, SB 2) for their antibacterial effect and bonding stability to dentin. EGCG-3Me was isolated and purified with column chromatography and preparative high performance liquid chromatography. EGCG and EGCG-3Me were incorporated separately into the adhesive SB 2 at concentrations of 200, 400, and 600 µg/mL. The effect of cured adhesives on the growth of Streptococcus mutans ( S. mutans ) was determined with scanning electron microscopy and confocal laser scanning microscopy; the biofilm of bacteria was further quantified via optical density 600 values. The inhibition of EGCG and EGCG-3Me on dentin-originated collagen proteases activities was evaluated with a proteases fluorometric assay kit. The degree of conversion (DC) of the adhesives was tested with micro-Raman spectrum. The immediate and post-thermocycling (5000 cycles) bond strength was assessed through Microtensile Bond Strength (MTBS) test. Cured EGCG/EGCG-3Me modified adhesives inhibit the growth of S. mutans in a concentration-dependent manner. The immediate MTBS of SB 2 was not compromised by EGCG/EGCG-3Me modification. EGCG/EGCG-3Me modified adhesive had higher MTBS than SB 2 after thermocycling, showing no correlation with concentration. The DC of the adhesive system was affected depending on the concentration of EGCG/EGCG-3Me and the depth of the hybrid layer. EGCG/EGCG-3Me modified adhesives could inhibit S. mutans adhesion to dentin-resin interface, and maintain the bonding stability. The adhesive modified with 400 µg/mL EGCG-3Me showed antibacterial effect and enhanced bonding stability without affect the DC of adhesive.

Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments

PubMed Central

Chu, Chenyu; Deng, Jia

2017-01-01

Epigallocatechin-3-gallate (EGCG), a component extracted from green tea, has been proved to have multiple effects on human pathological and physiological processes, and its mechanisms are discrepant in cancer, vascularity, bone regeneration, and nervous system. Although there are multiple benefits associated with EGCG, more and more challenges are still needed to get through. For example, EGCG shows low bioactivity via oral administration. This review focuses on effects of EGCG, including anti-cancer, antioxidant, anti-inflammatory, anticollagenase, and antifibrosis effects, to express the potential of EGCG and necessity of further studies in this field. PMID:28884125

Multifunctional mussel-inspired copolymerized epigallocatechin gallate (EGCG)/arginine coating: the potential as an ad-layer for vascular materials.

PubMed

Luo, Rifang; Tang, Linlin; Xie, Lingxia; Wang, Jin; Huang, Nan; Wang, Yunbing

2016-12-01

Surface properties are considered to be important factors in addressing proper functionalities. In this paper, a multifunctional mussel-inspired coating was prepared via the direct copolymerization of epigallocatechin gallate (EGCG) and arginine. The coating formation was confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectra. The EGCG/arginine coating contained diverse functional groups like amines, phenols and carboxyls, whose densities were also tunable. Such mussel-inspired coating could also be applied as an ad-layer for its secondary reactivity, demonstrated by quartz crystal microbalance technique. Moreover, the tunable surface density of phenols showed potential ability in modulating endothelial cell and smooth muscle cell viability. The coatings rich in phenols presented excellent free radical scavenging property. Current results strongly indicated the potential of EGCG/arginine coatings to be applied as an ad-layer for vascular materials.

Epigallocatechin-3-Gallate (EGCG) Attenuates Traumatic Brain Injury by Inhibition of Edema Formation and Oxidative Stress.

PubMed

Zhang, Bo; Wang, Bing; Cao, Shuhua; Wang, Yongqiang

2015-11-01

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3-gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-1β and TNF-α mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of p47(phox) translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress.

Epigallocatechin gallate (EGCG) stimulates autophagy in vascular endothelial cells: a potential role for reducing lipid accumulation.

PubMed

Kim, Hae-Suk; Montana, Vedrana; Jang, Hyun-Ju; Parpura, Vladimir; Kim, Jeong-a

2013-08-02

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has beneficial effects in the prevention of cardiovascular disease. Autophagy is a cellular process that protects cells from stressful conditions. To determine whether the beneficial effect of EGCG is mediated by a mechanism involving autophagy, the roles of the EGCG-stimulated autophagy in the context of ectopic lipid accumulation were investigated. Treatment with EGCG increased formation of LC3-II and autophagosomes in primary bovine aortic endothelial cells (BAEC). Activation of calmodulin-dependent protein kinase kinase β was required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation was significantly impaired by knockdown of calmodulin-dependent protein kinase kinase β. This effect is most likely due to cytosolic Ca(2+) load. To determine whether EGCG affects palmitate-induced lipid accumulation, the effects of EGCG on autophagic flux and co-localization of lipid droplets and autophagolysosomes were examined. EGCG normalized the palmitate-induced impairment of autophagic flux. Accumulation of lipid droplets by palmitate was markedly reduced by EGCG. Blocking autophagosomal degradation opposed the effect of EGCG in ectopic lipid accumulation, suggesting the action of EGCG is through autophagosomal degradation. The mechanism for this could be due to the increased co-localization of lipid droplets and autophagolysosomes. Co-localization of lipid droplets with LC3 and lysosome was dramatically increased when the cells were treated with EGCG and palmitate compared with the cells treated with palmitate alone. Collectively, these findings suggest that EGCG regulates ectopic lipid accumulation through a facilitated autophagic flux and further imply that EGCG may be a potential therapeutic reagent to prevent cardiovascular complications.

Optimization on condition of epigallocatechin-3-gallate (EGCG) nanoliposomes by response surface methodology and cellular uptake studies in Caco-2 cells

NASA Astrophysics Data System (ADS)

Luo, Xiaobo; Guan, Rongfa; Chen, Xiaoqiang; Tao, Miao; Ma, Jieqing; Zhao, Jin

2014-06-01

The major component in green tea polyphenols, epigallocatechin-3-gallate (EGCG), has been demonstrated to prevent carcinogenesis. To improve the effectiveness of EGCG, liposomes were used as a carrier in this study. Reverse-phase evaporation method besides response surface methodology is a simple, rapid, and beneficial approach for liposome preparation and optimization. The optimal preparation conditions were as follows: phosphatidylcholine-to-cholesterol ratio of 4.00, EGCG concentration of 4.88 mg/mL, Tween 80 concentration of 1.08 mg/mL, and rotary evaporation temperature of 34.51°C. Under these conditions, the experimental encapsulation efficiency and size of EGCG nanoliposomes were 85.79% ± 1.65% and 180 nm ± 4 nm, which were close with the predicted value. The malondialdehyde value and the release test in vitro indicated that the prepared EGCG nanoliposomes were stable and suitable for more widespread application. Furthermore, compared with free EGCG, encapsulation of EGCG enhanced its inhibitory effect on tumor cell viability at higher concentrations.

Extraction of Epigallocatechin Gallate and Epicatechin Gallate from Tea Leaves Using β-Cyclodextrin.

PubMed

Cui, Lu; Liu, Yuxuan; Liu, Ting; Yuan, Yahong; Yue, Tianli; Cai, Rui; Wang, Zhouli

2017-02-01

Use of organic solvents to extract phenolic compounds from plants may result in environmental pollution and cause health problems in persons. Replacing organic extraction solvents by green extracting agents without affecting the extraction yield is one of the most pressing problems to be solved. The aim of this study is to evaluate the capacity of β-cyclodextrin (β-CD) to recover phenolic compounds from tea leaves. The extract obtained using the ethanol/water mixture presented the highest total phenolic content, followed by those obtained using β-CD solution and water. HPLC analysis of the extracts showed that the addition of β-CD to the extracting agent had a selective effect on the extraction of epigallocatechin gallate (EGCG) and epicatechin gallate (ECG). The extraction yield of EGCG and ECG using 15 g/L β-CD were higher than that obtained using water and 50% ethanol. Molecular docking results indicated that the molecules of EGCG and ECG were more inclined to interact with β-CD than epigallocatechin, epicatechin, and gallocatechin. The impact of β-CD concentration, temperature, and time on EGCG and ECG extraction from tea leaves was investigated and the maximum amount of EGCG (118.7 mg/g) and ECG (54.6 mg/g) were achieved when extracted with 25 g/L aqueous β-CD solution at 60 °C for 60 min. The present study indicates that aqueous β-CD can be used as an alternative to organic solvents to recover EGCG and ECG from tea leaves. © 2017 Institute of Food Technologists®.

Therapeutic Potential of Epigallocatechin Gallate Nanodelivery Systems

PubMed Central

Granja, Andreia; Frias, Iúri; Neves, Ana Rute; Reis, Salette

2017-01-01

Nowadays, the society is facing a large health problem with the rising of new diseases, including cancer, heart diseases, diabetes, neurodegenerative diseases, and obesity. Thus, it is important to invest in substances that enhance the health of the population. In this context, epigallocatechin gallate (EGCG) is a flavonoid found in many plants, especially in tea. Several studies support the notion that EGCG has several benefits in fighting cancer, heart diseases, diabetes, and obesity, among others. Nevertheless, the poor intestinal absorbance and instability of EGCG constitute the main drawback to use this molecule in prevention and therapy. The encapsulation of EGCG in nanocarriers leads to its enhanced stability and higher therapeutic effects. A comprehensive review of studies currently available on the encapsulation of EGCG by means of nanocarriers will be addressed. PMID:28791306

Epigallocatechin-3-gallate (EGCG)-stabilized selenium nanoparticles coated with Tet-1 peptide to reduce amyloid-β aggregation and cytotoxicity.

PubMed

Zhang, Jingnan; Zhou, Xianbo; Yu, Qianqian; Yang, Licong; Sun, Dongdong; Zhou, Yanhui; Liu, Jie

2014-06-11

Alzheimer's disease (AD), the most common neurodegenerative disease, is caused by an accumulation of amyloid-β (Aβ) plaque deposits in the brains. Evidence is increasingly showing that epigallocatechin-3-gallate (EGCG) can partly protect cells from Aβ-mediated neurotoxicity by inhibiting Aβ aggregation. In order to better understand the process of Aβ aggregation and amyloid fibril disaggregation and reduce the cytotoxicity of EGCG at high doses, we attached EGCG onto the surface of selenium nanoparticles (EGCG@Se). Given the low delivery efficiency of EGCG@Se to the targeted cells and the involvement of selenoprotein in antioxidation and neuroprotection, which are the key factors for preventing the onset and progression of AD, we synthesized EGCG-stabilized selenium nanoparticles coated with Tet-1 peptide (Tet-1-EGCG@Se, a synthetic selenoprotein analogue), considering the affinity of Tet-1 peptide to neurons. We revealed that Tet-1-EGCG@Se can effectively inhibit Aβ fibrillation and disaggregate preformed Aβ fibrils into nontoxic aggregates. In addition, we found that both EGCG@Se and Tet-1-EGCG@Se can label Aβ fibrils with a high affinity, and Tet-1 peptides can significantly enhance the cellular uptake of Tet-1-EGCG@Se in PC12 cells rather than in NIH/3T3 cells.

Effect of (-)-epigallocatechin gallate (EGCG) extracted from green tea in reducing the formation of acrylamide during the bread baking process.

PubMed

Fu, Zhengjie; Yoo, Michelle J Y; Zhou, Weibiao; Zhang, Lei; Chen, Yutao; Lu, Jun

2018-03-01

This is the first study to investigate the extent of reduction in acrylamide formation during baking with the addition of (-)-epigallocatechin gallate (EGCG) extracted from green tea, and to determine whether EGCG influences the texture and colour attributes of bread, or interacts with other ingredients. EGCG powders were added to white bread formulations at the concentrations of 3.3, 6.6 and 9.9g·kg -1 . The amount of acrylamide in the bread was analysed using liquid chromatography-mass spectrometry. EGCG addition significantly reduced the acrylamide formation by 37% compared to the control and decreased the moisture content of the bread by 6%. It did not affect its texture attribute, but increased the lightness and the yellowness and decreased the redness of bread crust (with contrasting results in crumb). It also decreased granule size and porosity. In conclusion, EGCG fortification is a feasible method to decrease acrylamide formation in baked bread. Copyright © 2017 Elsevier Ltd. All rights reserved.

EPIGALLOCATECHIN-3-GALLATE (EGCG), A GREEN TEA POLYPHENOL, SUPPRESSES HEPATIC GLUCONEOGENESIS THROUGH 5′-AMP-ACTIVATED PROTEIN KINASE

PubMed Central

Collins, Qu Fan; Liu, Hui-Yu; Pi, Jingbo; Liu, Zhenqi; Quon, Michael J.; Cao, Wenhong

2008-01-01

Epigallocatechin-3-gallate (EGCG), a main catechin of green tea, has been suggested to inhibit hepatic gluconeogenesis. However, the exact role and related mechanism have not been established. In this study, we examined the role of EGCG in hepatic gluconeogenesis at concentrations that are reachable by ingestion of pure EGCG or green tea, and are not toxic to hepatocytes. Our results show in isolated hepatocytes that EGCG at relatively low concentrations (≤ 1 μM) inhibited glucose production via gluconeogenesis and expression of key gluconeogenic genes. EGCG was not toxic at these concentrations while demonstrating significant cytotoxicity at 10 μM and higher concentrations. EGCG at 1 μM or lower concentrations effective in suppressing hepatic gluconeogenesis did not activate the insulin signaling pathway, but activated 5′-AMP-activated protein kinase (AMPK). The EGCG suppression of hepatic gluconeogenesis was prevented by blockade of AMPK activity. In defining the mechanism by which EGCG activates AMPK, we found that the EGCG activation of AMPK was mediated by the Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Furthermore, our results show that the EGCG activation of AMPK and EGCG suppression of hepatic gluconeogenesis were both dependent on production of reactive oxygen species (ROS), which was a known activator of CaMKK. Together, our results demonstrate an inhibitory role for EGCG in hepatic gluconeogenesis and shed new light on the mechanism by which EGCG suppresses gluconeogenesis. PMID:17724029

Functional Properties of Novel Epigallocatechin Gallate Glucosides Synthesized by Using Dextransucrase from Leuconostoc mesenteroides B-1299CB4.

PubMed

Kim, Jiyoun; Nguyen, Thi Thanh Hanh; Kim, Nahyun M; Moon, Young-Hwan; Ha, Jung-Min; Park, Namhyeon; Lee, Dong-Gu; Hwang, Kyeong-Hwan; Park, Jun-Seong; Kim, Doman

2016-12-07

Epigallocatechin gallate (EGCG) is the most abundant catechin found in the leaves of green tea, Camellia sinensis. In this study, novel epigallocatechin gallate-glucocides (EGCG-Gs) were synthesized by using dextransucrase from Leuconostoc mesenteroides B-1299CB4. Response surface methodology was adopted to optimize the conversion of EGCG to EGCG-Gs, resulting in a 91.43% conversion rate of EGCG. Each EGCG-G was purified using a C 18 column. Of nine EGCG-Gs identified by nuclear magnetic resonance analysis, five EGCG-Gs (2 and 4-7) were novel compounds with yields of 2.2-22.6%. The water solubility of the five novel compounds ranged from 229.7 to 1878.5 mM. The 5'-OH group of EGCG-Gs expressed higher antioxidant activities than the 4'-OH group of EGCG-Gs. Furthermore, glucosylation at 7-OH group of EGCG-Gs was found to be responsible for maintaining tyrosinase inhibitory activity and increasing browning-resistant activities.

Epigallocatechin-3-gallate (EGCG) inhibits imiquimod-induced psoriasis-like inflammation of BALB/c mice.

PubMed

Zhang, Shuangshuang; Liu, Xiangdong; Mei, Lihong; Wang, Hongfeng; Fang, Fang

2016-08-31

Psoriasis is a chronic inflammatory immune disease with undefined pathogenesis. It is associated with T cells, and the IL-23/IL17 axis is believed to be crucial in the pathogenesis. The present treatments have side effects that influence the compliance of patients. Tea polyphenol is extracted from tea polyphenols, and its main active ingredient is Epigallocatechin-3-gallate (EGCG), which has been shown to have antioxidant, anti-tumor, and anti-ultraviolet radiation effects. Here, we aim to report that EGCG can inhibit imiquimod (IMQ)-induced psoriasis-like inflammation. We used BALB/c mice, which were topically treated with IMQ for 6 consecutive days, as a psoriasis mouse model. Topical application of EGCG and treatment with EGCG were conducted in the experiments. Then observed the effects of the two methods on psoriasis-like mice dermatitis. Statistics are presented as the means ± standard error of mean (SEM) and compared using unpaired two-tailed Student's t tests or one-way ANOVA. Topical application of EGCG alleviated psoriasiform dermatitis, improved the skin pathological structure by reduce the expression of epidermal PCNA, promoted the expression of caspase-14. Treatment with EGCG attenuated skin inflammation, accompanied by reduced infiltrations of T cells; reduced percentages of CD11c(+) DC in the composition of immunocytes of spleens; reduced levels of interleukin (IL)-17A, IL-17F, IL-22, IL-23 and malondialdehyde (MDA) in plasma; increased percentages of CD4(+) T cells in the composition of immunocytes of spleens; and increased bioactivities of superoxide dismutase (SOD) and catalase (CAT) in plasma. All the results demonstrated that EGCG had anti-inflammatory, immune regulatory and antioxidant effects. It is a promising intervention in psoriasis in the future.

Epigallocatechin-3-Gallate (EGCG) Reduces Rotenone Effect on Stallion Sperm-Zona Pellucida Heterologous Binding.

PubMed

Plaza Dávila, M; Bucci, D; Galeati, G; Peña, F J; Mari, G; Giaretta, E; Tamanini, C; Spinaci, M

2015-12-01

Stallion spermatozoa are highly dependent on oxidative phosphorylation for ATP production to achieve normal sperm function and to fuel the motility. The aim of this study was to evaluate the response of equine sperm under capacitating conditions to the inhibition of mitochondrial complex I by rotenone and to test whether epigallocatechin-3-gallate (EGCG), a natural polyphenol component of green tea, could counteract this effect. After 2-h incubation of stallion spermatozoa in modified Tyrode's medium, rotenone (100 nm, 500 nm and 5 μm) and EGCG (10, 20 and 60 μm), alone or in combination, did not induce any significant difference on the percentage of viable cells, live sperm with active mitochondria and spermatozoa with intact acrosome. The inhibition of complex I of mitochondrial respiratory chain of stallion sperm with rotenone exerted a negative effect on heterologous ZP binding ability. EGCG at the concentrations of 10 and 20 μm (but not of 60 μm) induced a significant increase in the number of sperm bound to the ZP compared with that for control. Moreover, when stallion sperm were treated with rotenone 100 nm, the presence of EGCG at all the concentrations tested (10, 20 and 60 μm) significantly increased the number of sperm bound to the ZP up to control levels, suggesting that this green tea polyphenol is able to reduce the toxicity of rotenone. © 2015 Blackwell Verlag GmbH.

Physicochemical characterization of epigallocatechin gallate lipid nanoparticles (EGCG-LNs) for ocular instillation.

PubMed

Fangueiro, Joana F; Andreani, Tatiana; Fernandes, Lisete; Garcia, Maria L; Egea, Maria A; Silva, Amélia M; Souto, Eliana B

2014-11-01

The encapsulation of epigallocatechin gallate (EGCG) in lipid nanoparticles (LNs) could be a suitable approach to avoid drug oxidation and epimerization, which are common processes that lead to low bioavailability of the drug limiting its therapeutic efficacy. The human health benefits of EGCG gained much interest in the pharmaceutical field, and so far there are no studies reporting its encapsulation in LNs. The purpose of this study has been the development of an innovative system for the ocular delivery of EGCG using LNs as carrier for the future treatment of several diseases, such as dry eye, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy and macular oedema. LNs dispersions have been produced by multiple emulsion technique and previously optimized by a factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, two distinct cationic lipids were used, namely, cetyltrimethylammonium bromide (CTAB) and dimethyldioctadecylammonium bromide (DDAB). EGCG has been successfully loaded in the LNs dispersions and the nanoparticles analysis over 30 days of storage time predicted a good physicochemical stability. The particles were found to be in the nanometer range (<300 nm) and all the evaluated parameters, namely pH, osmolarity and viscosity, were compatible to the ocular administration. The evaluation of the cationic lipid used was compared regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. The results show that different lipids lead to different characteristics mainly associated with the acyl chain composition, i.e. double lipid shows to have influence in the crystallization and stability. Despite the recorded differences between DTAB and DDAB, both cationic LNs seem to fit the parameters for ocular drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Epigallocatechin-3-gallate (EGCG) protects skin cells from ionizing radiation via heme oxygenase-1 (HO-1) overexpression.

PubMed

Zhu, Wei; Xu, Jing; Ge, Yangyang; Cao, Han; Ge, Xin; Luo, Judong; Xue, Jiao; Yang, Hongying; Zhang, Shuyu; Cao, Jianping

2014-11-01

Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant and free radical scavenger that may have therapeutic applications for the treatment of many disorders. Radiation therapy is widely used for the treatment of various types of cancers; however, radiation-induced skin injury remains a serious concern. EGCG has not yet been reported as protecting skin cells against ionizing radiation. In the present study, we investigated whether EGCG confers cytoprotection against ionizing radiation. We found that, compared with the control, pretreatment with EGCG significantly enhanced the viability of human skin cells that were irradiated with X-rays, and decreased apoptosis induced by X-ray irradiation. Mito-Tracker assay showed that EGCG suppressed the damage to mitochondria induced by ionizing radiation via upregulation of SOD2. Reactive oxygen species (ROS) in HaCaT cells were significantly reduced when pretreated with EGCG before irradiation. Radiation-induced γH2AX foci, which are representative of DNA double-strand breaks, were decreased by pretreatment with EGCG. Furthermore, EGCG induced the expression of the cytoprotective molecule heme oxygenase-1 (HO-1) in a dose-dependent manner via transcriptional activation. HO-1 knockdown or treatment with the HO-1 inhibitor tin protoporphyrin (SnPPIX) reversed the protective role of EGCG, indicating an important role for HO-1. These results suggest that EGCG offers a new strategy for protecting skin against ionizing radiation. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice.

PubMed

Franko, Andras; Rodriguez Camargo, Diana C; Böddrich, Annett; Garg, Divita; Rodriguez Camargo, Andres; Rathkolb, Birgit; Janik, Dirk; Aichler, Michaela; Feuchtinger, Annette; Neff, Frauke; Fuchs, Helmut; Wanker, Erich E; Reif, Bernd; Häring, Hans-Ulrich; Peter, Andreas; Hrabě de Angelis, Martin

2018-01-18

The formation of amyloid fibrils by human islet amyloid polypeptide protein (hIAPP) has been implicated in pancreas dysfunction and diabetes. However, efficient treatment options to reduce amyloid fibrils in vivo are still lacking. Therefore, we tested the effect of epigallocatechin gallate (EGCG) on fibril formation in vitro and in vivo. To determine the binding of hIAPP and EGCG, in vitro interaction studies were performed. To inhibit amyloid plaque formation in vivo, homozygous (tg/tg), hemizygous (wt/tg), and control mice (wt/wt) were treated with EGCG. EGCG bound to hIAPP in vitro and induced formation of amorphous aggregates instead of amyloid fibrils. Amyloid fibrils were detected in the pancreatic islets of tg/tg mice, which was associated with disrupted islet structure and diabetes. Although pancreatic amyloid fibrils could be detected in wt/tg mice, these animals were non-diabetic. EGCG application decreased amyloid fibril intensity in wt/tg mice, however it was ineffective in tg/tg animals. Our data indicate that EGCG inhibits amyloid fibril formation in vitro and reduces fibril intensity in non-diabetic wt/tg mice. These results demonstrate a possible in vivo effectiveness of EGCG on amyloid formation and suggest an early therapeutical application.

Evaluation of epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes and concerns on osteoblasts.

PubMed

Chu, Chenyu; Deng, Jia; Xiang, Lin; Wu, Yingying; Wei, Xiawei; Qu, Yili; Man, Yi

2016-10-01

Collagen membranes have ideal biological and mechanical properties for supporting infiltration and proliferation of osteoblasts and play a vital role in guided bone regeneration (GBR). However, pure collagen can lead to inflammation, resulting in progressive bone resorption. Therefore, a method for regulating the level of inflammatory cytokines at surgical sites is paramount for the healing process. Epigallocatechin-3-gallate (EGCG) is a component extracted from green tea with numerous biological activities including an anti-inflammatory effect. Herein, we present a novel cross-linked collagen membrane containing different concentrations of EGCG (0.0064%, 0.064%, and 0.64%) to regulate the level of inflammatory factors secreted by pre-osteoblast cells; improve cell proliferation; and increase the tensile strength, wettability, and thermal stability of collagen membranes. Scanning electron microscope images show that the surfaces of collagen membranes became smoother and the collagen fiber diameters became larger with EGCG treatment. Measurement of the water contact angle demonstrated that introducing EGCG improved membrane wettability. Fourier transform infrared spectroscopy analyses indicated that the backbone of collagen was intact, and the thermal stability was significant improved in differential scanning calorimetry. The mechanical properties of 0.064% and 0.64% EGCG-treated collagen membranes were 1.5-fold greater than those of the control. The extent of cross-linking was significantly increased, as determined by a 2,4,6-trinitrobenzenesulfonic acid solution assay. The Cell Counting Kit-8 (CCK-8) and live/dead assays revealed that collagen membrane cross-linked by 0.0064% EGCG induced greater cell proliferation than pure collagen membranes. Additionally, real-time polymerase chain reaction and enzyme-linked immunosorbent assay results showed that EGCG significantly affected the production of inflammatory factors secreted by MC3T3-E1 cells. Taken together, our

Assessment of extraction parameters on antioxidant capacity, polyphenol content, epigallocatechin gallate (EGCG), epicatechin gallate (ECG) and iriflophenone 3-C-β-glucoside of agarwood (Aquilaria crassna) young leaves.

PubMed

Tay, Pei Yin; Tan, Chin Ping; Abas, Faridah; Yim, Hip Seng; Ho, Chun Wai

2014-08-14

The effects of ethanol concentration (0%-100%, v/v), solid-to-solvent ratio (1:10-1:60, w/v) and extraction time (30-180 min) on the extraction of polyphenols from agarwood (Aquilaria crassna) were examined. Total phenolic content (TPC), total flavonoid content (TFC) and total flavanol (TF) assays and HPLC-DAD were used for the determination and quantification of polyphenols, flavanol gallates (epigallocatechin gallate--EGCG and epicatechin gallate--ECG) and a benzophenone (iriflophenone 3-C-β-glucoside) from the crude polyphenol extract (CPE) of A. crassna. 2,2'-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was used to evaluate the antioxidant capacity of the CPE. Experimental results concluded that ethanol concentration and solid-to-solvent ratio had significant effects (p<0.05) on the yields of polyphenol and antioxidant capacity. Extraction time had an insignificant influence on the recovery of EGCG, ECG and iriflophenone 3-C-β-glucoside, as well as radical scavenging capacity from the CPE. The extraction parameters that exhibited maximum yields were 40% (v/v) ethanol, 1:60 (w/v) for 30 min where the TPC, TFC, TF, DPPH, EGCG, ECG and iriflophenone 3-C-β-glucoside levels achieved were 183.5 mg GAE/g DW, 249.0 mg QE/g DW, 4.9 mg CE/g DW, 93.7%, 29.1 mg EGCG/g DW, 44.3 mg ECG/g DW and 39.9 mg iriflophenone 3-C-β-glucoside/g DW respectively. The IC50 of the CPE was 24.6 mg/L.

Identification of epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3''Me) and amino acid profiles in various tea (Camellia sinensis L.) cultivars.

PubMed

Ji, Hyang-Gi; Lee, Yeong-Ran; Lee, Min-Seuk; Hwang, Kyeng Hwan; Kim, Eun-Hee; Park, Jun Seong; Hong, Young-Shick

2017-10-01

This article includes experimental data on the identification of epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3''Me) by 2-dimensional (2D) proton ( 1 H) NMR analysis and on the information of amino acid and catechin compound profiles by HPLC analysis in leaf extracts of various tea cultivars. These data are related to the research article " Metabolic phenotyping of various tea (Camellia sinensis L.) cultivars and understanding of their intrinsic metabolism " (Ji et al., 2017) [1]. The assignment for EGCG3x''Me by 1 H NMR analysis was also confirmed with spiking experiment of its pure chemical.

The effect of epigallocatechin-3-gallate (EGCG) on human alveolar bone cells both in vitro and in vivo.

PubMed

Mah, Yon-Joo; Song, Je Seon; Kim, Seong-Oh; Lee, Jae-Ho; Jeon, Mijeong; Jung, Ui-Won; Moon, Seok Jun; Kim, Jeong-Hee; Choi, Hyung-Jun

2014-05-01

The effects of epigallocatechin-3-gallate (EGCG), a major catechin in green tea, on human and mouse osteoblasts remain controversial. This study investigated the direct effects of EGCG on human alveolar bone-derived cells (hABCs) both in vitro and in vivo. hABCs which were collected from eight children (aged 7-9 years, seven males and one female) were treated with EGCG at various concentrations (1, 5, 10, 25, and 50μM), and a proliferation assay, flow cytometric analysis for apoptosis evaluation, migration assay, and in vitro osteogenic differentiation were performed. hABCs that were pretreated with 10μM EGCG and mixed with calcium phosphate carrier combined with EGCG (0.1, 0.5, or 1.5mg) in vivo were transplanted into immunodeficient mouse. Histological staining, quantitative gene expressions, and alkaline phosphatase activity were evaluated in the retrieved transplants. The proliferation and migration were decreased when EGCG was present at over 25μM. The osteogenic differentiation increased slightly when EGCG was present at up to 10μM, and clearly decreased for higher concentrations of EGCG. In vivo, the potential for hard-tissue formation was slightly higher for the group with 0.1mg of EGCG than for the control group, and decreased sharply for higher concentrations of EGCG. The present observations suggest that EGCG at a low concentration can slightly enhance the osteogenic effect in vivo, whereas at a higher concentration it can prevent the osteogenic differentiation of hABCs both in vitro and in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

The spectral properties of (-)-epigallocatechin 3-O-gallate (EGCG) fluorescence in different solvents: dependence on solvent polarity.

PubMed

Snitsarev, Vladislav; Young, Michael N; Miller, Ross M S; Rotella, David P

2013-01-01

(-)-Epigallocatechin 3-O-gallate (EGCG) a molecule found in green tea and known for a plethora of bioactive properties is an inhibitor of heat shock protein 90 (HSP90), a protein of interest as a target for cancer and neuroprotection. Determination of the spectral properties of EGCG fluorescence in environments similar to those of binding sites found in proteins provides an important tool to directly study protein-EGCG interactions. The goal of this study is to examine the spectral properties of EGCG fluorescence in an aqueous buffer (AB) at pH=7.0, acetonitrile (AN) (a polar aprotic solvent), dimethylsulfoxide (DMSO) (a polar aprotic solvent), and ethanol (EtOH) (a polar protic solvent). We demonstrate that EGCG is a highly fluorescent molecule when excited at approximately 275 nm with emission maxima between 350 and 400 nm depending on solvent. Another smaller excitation peak was found when EGCG is excited at approximately 235 nm with maximum emission between 340 and 400 nm. We found that the fluorescence intensity (FI) of EGCG in AB at pH=7.0 is significantly quenched, and that it is about 85 times higher in an aprotic solvent DMSO. The Stokes shifts of EGCG fluorescence were determined by solvent polarity. In addition, while the emission maxima of EGCG fluorescence in AB, DMSO, and EtOH follow the Lippert-Mataga equation, its fluorescence in AN points to non-specific solvent effects on EGCG fluorescence. We conclude that significant solvent-dependent changes in both fluorescence intensity and fluorescence emission shifts can be effectively used to distinguish EGCG in aqueous solutions from EGCG in environments of different polarity, and, thus, can be used to study specific EGCG binding to protein binding sites where the environment is often different from aqueous in terms of polarity.

Epigallocatechin Gallate (EGCG) Decorating Soybean Seed Ferritin as a Rutin Nanocarrier with Prolonged Release Property in the Gastrointestinal Tract.

PubMed

Yang, Rui; Sun, Guoyu; Zhang, Min; Zhou, Zhongkai; Li, Quanhong; Strappe, Padraig; Blanchard, Chris

2016-09-01

The instability and low bioavailability of polyphenols limit their applications in food industries. In this study, epigallocatechin gallate (EGCG) and soybean seed ferritin deprived of iron (apoSSF) were fabricated as a combined double shell material to encapsulate rutin flavonoid molecules. Firstly, due to the reversible assembly characteristics of phytoferritin, rutin was successfully encapsulated within apoSSF to form a ferritin-rutin complex (FR) with an average molar ratio of 28.2: 1 (rutin/ferritin). The encapsulation efficiency and loading capacity of rutin were 18.80 and 2.98 %, respectively. EGCG was then bound to FR to form FR-EGCG composites (FRE), and the binding number of EGCG was 27.30 ± 0.68 with a binding constant K of (2.65 ± 0.11) × 10(4) M(-1). Furthermore, FRE exhibited improved rutin stability, and displayed prolonged release of rutin in simulated gastrointestinal tract fluid, which may be attributed to the external attachment of EGCG to the ferritin cage potentially reducing enzymolysis in GI fluid. In summary, this work demonstrates a novel nanocarrier for stabilization and sustained release of bioactive polyphenols.

(-)-Epigallocatechin gallate (EGCG)-nanoethosomes as a transdermal delivery system for docetaxel to treat implanted human melanoma cell tumors in mice.

PubMed

Liao, Bingwu; Ying, Hao; Yu, Chenhuan; Fan, Zhaoyang; Zhang, Weihua; Shi, John; Ying, Huazhong; Ravichandran, Nagaiya; Xu, Yongquan; Yin, Junfeng; Jiang, Yongwen; Du, Qizhen

2016-10-15

(-)-Epigallocatechin-3-O-gallate (EGCG), a versatile natural product in fresh tea leaves and green tea, has been investigated as a preventative treatment for cancers and cardiovascular disease. The objective of this study was to develop EGCG-nanoethosomes for transdermal delivery and to evaluate them for treating subcutaneously implanted human melanoma cell tumors. EGCG-nanoethosomes, composed of 0.2% EGCG, 2% soybean phosphatidylcholine, 30% ethanol, 1% Tween-80 and 0.1% sugar esters, were prepared and characterized using laser transmission electron microscopy. These nanoethosomes were smoother and more compact than basic-nanoethosomes with the same components except for EGCG. The effectiveness of transdermal delivery by EGCG-nanoethosomes was demonstrated in an in vitro permeability assay system using mouse skin. The inhibitory effect of docetaxel (DT) loaded in EGCG-nanoethosomes (DT-EGCG-nanoethosomes) was analyzed by monitoring growth of a subcutaneously implanted tumor from A-375 human melanoma cells in mice. Mice treated with DT-EGCG-nanoethosomes exhibited a significant therapeutic effect, with tumors shrinking, on average, by 31.5% of initial volumes after 14 d treatment. This indicated a potential for treating skin cancer. In a pharmacokinetic study, transdermal delivery by DT-EGCG-nanoethosomes enabled sufficient DT exposure to the tumor. Together, these findings indicated that EGCG-nanoethosomes have great potential as drug carriers for transdermal delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

The Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCg) Attenuates Skeletal Muscle Atrophy in a Rat Model of Sarcopenia.

PubMed

Meador, B M; Mirza, K A; Tian, M; Skelding, M B; Reaves, L A; Edens, N K; Tisdale, M J; Pereira, S L

2015-01-01

Sarcopenia-the loss of muscle mass and functionality occurring with age-is a pervasive problem with few effective treatments beyond exercise. We examined the ability of the green tea catechin, epigallocatechin-3-gallate (EGCg), to impact muscle mass and the molecular pathway involved in muscle atrophy in a rat model of sarcopenia. 20-month-old Sprague-Dawley rats were treated for 8 weeks with control diet or control plus 200mg/kg body weight of EGCg diet. EGCg-supplemented animals had significantly greater gastrocnemius muscle mass than the aged controls, and showed a trend for increased muscle fiber cross-sectional areas (CSA) (p=0.06). These changes were associated with significantly lower protein expressions of the intramuscular 19S and 20S proteasome subunits and the MuRF1 and MAFbx ubiquitin ligases in the EGCg-treated animals. Proteasome activity as determined by 'Chymotrypsin-like' enzyme activity was also significantly reduced by EGCg. Muscle mRNA expression of IL-15 and IGF-1 were significantly increased in the EGCg group vs. the aged controls. In comparison to younger adult animals (6 month), the protein expression of 19S, 20S, MuRF1, MAFbx, and myostatin were increased between approximately 4- and 12-fold in the aged controls, but only up to ~2-fold in the aged EGCg animals. EGCg supplementation was able to preserve muscle in sarcopenic rats, partly through attenuating protein degradation via the ubiquitin-proteasome pathway, together with increased expression of anabolic factors.

Separation and purification of epigallocatechin-3-gallate (EGCG) from green tea using combined macroporous resin and polyamide column chromatography.

PubMed

Jin, Xin; Liu, Mingyan; Chen, Zaixing; Mao, Ruikun; Xiao, Qinghuan; Gao, Hua; Wei, Minjie

2015-10-01

Epigallocatechin-3-gallate (EGCG) is a major bioactive ingredient of green tea that produces beneficial neuroprotective effects. In this paper, to optimize the EGCG enrichment, thirteen macroporous resins with different chemical and physical properties were systemically evaluated. Among the thirteen tested resins, the H-bond resin HPD826 exhibited best adsorption/desorption capabilities and desorption ratio, as well as weakest affinity for caffeine. The absorption of EGCG on the HPD826 resin followed the pseudo-second-order kinetics and Langmuir isotherm model. The separation parameters of EGCG were optimized by dynamic adsorption/desorption experiments with the HPD826 resin column. Under the optimal condition, the content of EGCG in the 30% ethanol eluent increased by 5.8-fold from 7.7% to 44.6%, with the recovery yield of 72.1%. After further purification on a polyamide column, EGCG with 74.8% purity was obtained in the 40-50% ethanol fraction with a recovery rate of 88.4%. In addition, EGCG with 95.1% purity could be easily obtained after one-step crystallization in distilled water. Our study suggests that the combined macroporous resin and polyamide column chromatography is a simple method for large-scale separation and purification of EGCG from natural plants for food and pharmaceutical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Metabolic interactions between cysteamine and epigallocatechin gallate.

PubMed

Izzo, Valentina; Pietrocola, Federico; Sica, Valentina; Durand, Sylvère; Lachkar, Sylvie; Enot, David; Bravo-San Pedro, José Manuel; Chery, Alexis; Esposito, Speranza; Raia, Valeria; Maiuri, Luigi; Maiuri, Maria Chiara; Kroemer, Guido

2017-02-01

Phase II clinical trials indicate that the combination of cysteamine plus epigallocatechin gallate (EGCG) is effective against cystic fibrosis in patients bearing the most frequent etiological mutation (CFTRΔF508). Here, we investigated the interaction between both agents on cultured respiratory epithelia cells from normal and CFTRΔF508-mutated donors. We observed that the combination of both agents affected metabolic circuits (and in particular the tricarboxylic acid cycle) in a unique way and that cysteamine plus EGCG reduced cytoplasmic protein acetylation more than each of the 2 components alone. In a cell-free system, protein cross-linking activity of EGCG was suppressed by cysteamine. Finally, EGCG was able to enhance the conversion of cysteamine into taurine in metabolic flux experiments. Altogether, these results indicate that multiple pharmacological interactions occur between cysteamine and EGCG, suggesting that they contribute to the unique synergy of both agents in restoring the function of mutated CFTRΔF508.

Metabolic interactions between cysteamine and epigallocatechin gallate

PubMed Central

Izzo, Valentina; Pietrocola, Federico; Sica, Valentina; Durand, Sylvère; Lachkar, Sylvie; Enot, David; Bravo-San Pedro, José Manuel; Chery, Alexis; Esposito, Speranza; Raia, Valeria; Maiuri, Luigi; Maiuri, Maria Chiara; Kroemer, Guido

2017-01-01

ABSTRACT Phase II clinical trials indicate that the combination of cysteamine plus epigallocatechin gallate (EGCG) is effective against cystic fibrosis in patients bearing the most frequent etiological mutation (CFTRΔF508). Here, we investigated the interaction between both agents on cultured respiratory epithelia cells from normal and CFTRΔF508-mutated donors. We observed that the combination of both agents affected metabolic circuits (and in particular the tricarboxylic acid cycle) in a unique way and that cysteamine plus EGCG reduced cytoplasmic protein acetylation more than each of the 2 components alone. In a cell-free system, protein cross-linking activity of EGCG was suppressed by cysteamine. Finally, EGCG was able to enhance the conversion of cysteamine into taurine in metabolic flux experiments. Altogether, these results indicate that multiple pharmacological interactions occur between cysteamine and EGCG, suggesting that they contribute to the unique synergy of both agents in restoring the function of mutated CFTRΔF508. PMID:28059601

Assessment of DNA damage and lipid peroxidation in diabetic mice: effects of propolis and epigallocatechin gallate (EGCG).

PubMed

Oršolić, Nada; Sirovina, Damir; Gajski, Goran; Garaj-Vrhovac, Vera; Jazvinšćak Jembrek, Maja; Kosalec, Ivan

2013-09-18

There is growing recognition that polyphenolic compounds present in many plants and natural products may have beneficial effects on human health. Propolis - a substance produced by honeybees - and catechins in tea, in particular (-)-epigallocatechin gallate (EGCG), are strong antioxidants that appear to have anti-obesity and anti-diabetic effects. The present study was designed to elucidate the anti-diabetic effect of the water-soluble derivative of propolis (WSDP), which contains phenolic acids as the main compounds, and EGCG in alloxan-induced (75mg/kg, iv) diabetes in mice. Intraperitoneal administration of EGCG or propolis at doses of 50mg/kg body weight (bw) to diabetic mice for a period of 7 days resulted in a significant increase in body weight and in haematological/immunological blood parameters, as well as in 100% survival of the mice. A significant decrease in lipid peroxidation in liver, kidney and brain tissue was also observed in diabetic mice treated with these two agents. Additionally, EGCG and propolis clearly reduced DNA damage in peripheral lymphocytes of diabetic mice. Our studies demonstrate the anti-oxidative and anti-inflammatory potential of WSDP and EGCG, which could exert beneficial effects against diabetes and the associated consequences of free-radical formation in kidney, liver, spleen and brain tissue. The results suggest that dietary supplementation with WSDP or EGCG could potentially contribute to nutritional strategies for the prevention and treatment of diabetes mellitus. Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibition of green tea polyphenol EGCG((-)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway.

PubMed

Yang, Chenggang; Du, Wenfeng; Yang, Daogui

2016-11-01

(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, could affect carcinogenesis and development of many cancers. However, the effects and underlying mechanisms of EGCG on gastric cancer remain unclear. We found that EGCG significantly inhibited proliferation and increased apoptosis of SGC-7901 cells in vitro. The decreased expressions of p-β-catenin(Ser552), p-GSK3β(S9) and β-catenin target genes were detected in SGC-7901 cells after treated by EGCG. XAV939 and β-catenin plasmid were further used to demonstrate the inhibition of EGCG on canonical Wnt/β-catenin signalling. Moreover, EGCG significantly inhibited gastric tumour growth in vivo by inhibiting Wnt/β-catenin signalling. Taken together, our findings establish that EGCG suppressed gastric cancer cell proliferation and demonstrate that this inhibitory effect is related to canonical Wnt/β-catenin signalling. This study raises a new insight into gastric cancer prevention and therapy, and provides evidence that green tea could be used as a nutraceutical beverage.

Attenuated migration by green tea extract (-)-epigallocatechin gallate (EGCG): involvement of 67 kDa laminin receptor internalization in macrophagic cells.

PubMed

Ren, Xuezhi; Guo, Xingzhi; Chen, Li; Guo, Minxia; Peng, Ning; Li, Rui

2014-08-01

Excessive activation of the microglia in the brain is involved in the development of several neurodegenerative diseases. Previous studies have indicated that (-)-epigallocatechin gallate (EGCG), a major active constituent of green tea, exhibits potent suppressive effects on the activation of microglia. As the 67 kDa laminin receptor (67LR) is a key element in cellular activation and migration, we investigated the effect of EGCG on cell migration and 67LR in lipopolysaccharide (LPS)-activated macrophagic RAW264.7 cells. The presence of EGCG (1-25 μM) markedly attenuated LPS-induced cell migration in a dose-dependent manner. However, the total amount of 67LR protein in the RAW264.7 cells was unaffected by EGCG, as revealed by Western blot analysis. In addition, confocal immunofluorescence microscopy indicated that EGCG caused a marked membrane translocation of 67LR from the membrane surface towards the cytoplasm. Cell-surface biotinylation analysis confirmed that EGCG induced a significant internalization of 67LR by 24-68% in a dose-dependent manner. This study helps to explain the pharmacological action of EGCG on 67LR, suggesting its potential use in the treatment of diseases associated with macrophage/microglia activation, such as neurodegenerative diseases and cancer.

Epigallocatechin gallate (EGCG) prevents H2O2-induced oxidative stress in primary rat retinal pigment epithelial cells.

PubMed

Cia, David; Vergnaud-Gauduchon, Juliette; Jacquemot, Nathalie; Doly, Michel

2014-09-01

To determine whether the green tea polyphenol epigallocatechin gallate (EGCG) could prevent H(2)O(2)-induced oxidative stress in primary rat retinal pigment epithelial cells. Primary cultures of retinal pigment epithelium (RPE) cells were established from Long-Evans newborn rats. RPE cells were pretreated with various concentrations of EGCG for 24 h before being exposed to hydrogen peroxide (H(2)O(2)) for 2 h to induce oxidative stress. Cell metabolic activity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death was quantified by flow cytometry using propidium iodide (PI). Treatment of RPE cells with EGCG alone does not affect the cell viability up to 50 µM. Exposure of RPE cells to 600 µM H(2)O(2) caused a significant decrease in cell viability; whereas pretreatment with 10, 25, and 50 µM EGCG significantly reduced this decrease in a dose-dependent manner. The proportion of PI-positive cells increased significantly in cultures treated with H(2)O(2) alone; whereas pretreatment of RPE cells with 50 µM EGCG significantly reduced H(2)O(2)-induced RPE cell death. Our study shows that EGCG pretreatment can protect primary rat RPE cells from H(2)O(2)-induced death. This suggests potential effect of EGCG in the prevention of retinal diseases associated with H(2)O(2)-induced oxidative stress.

Effects of O-methylated (-)-epigallocatechin gallate (EGCG) on LPS-induced osteoclastogenesis, bone resorption, and alveolar bone loss in mice.

PubMed

Tominari, Tsukasa; Ichimaru, Ryota; Yoshinouchi, Shosei; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Inada, Masaki; Miyaura, Chisato

2017-12-01

(-)-Epigallocatechin-3- O -gallate (EGCG), present in green tea, exhibits antioxidant and antiallergy effects. EGCG3″Me, a 3- O -methylated derivative of EGCG, has been reported to show similar biological functions; the inhibitory activity of EGCG3″Me in a mouse allergy model was more potent than that of EGCG, probably due to the efficiency of absorption from the intestine. However, the functional potency of these EGCGs is controversial in each disease model. We previously observed that EGCG suppressed inflammatory bone resorption and prevented alveolar bone loss in a mouse model of periodontosis. In this study, we examined the role of EGCG3″Me in bone resorption using a mouse model of periodontitis. Lipopolysaccharide (LPS)-induced osteoclast formation was suppressed by adding EGCG3″Me to cocultures of osteoblasts and bone marrow cells, and LPS-induced bone resorption was also inhibited by EGCG3″Me in calvarial organ cultures. EGCG3″Me acted on osteoblasts and suppressed prostaglandin E (PGE) production, which is critical for inflammatory bone resorption, by inhibiting the expression of COX-2 and mPGES-1, key enzymes for PGE synthesis. In osteoclast precursor macrophages, EGCG3″Me suppressed RANKL-dependent differentiation into mature osteoclasts. In a mouse model of periodontitis, LPS-induced bone resorption was suppressed by EGCG3″Me in organ culture of mouse alveolar bone, and the alveolar bone loss was further attenuated by the treatment of EGCG3″Me in the lower gingiva in vivo . EGCG3″Me may be a potential natural compound for the protection of inflammatory bone loss in periodontitis.

A prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG) serves as a novel angiogenesis inhibitor in endometrial cancer.

PubMed

Wang, Jianzhang; Man, Gene Chi Wai; Chan, Tak Hang; Kwong, Joseph; Wang, Chi Chiu

2018-01-01

Anti-angiogenesis effect of a prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG) in malignant tumors is not well studied. Here, we investigated how the treatment with Pro-EGCG inhibited tumor angiogenesis in endometrial cancer. Tumor xenografts of human endometrial cancer were established and subjected to microarray analysis after Pro-EGCG treatment. First, we showed Pro-EGCG inhibited tumor angiogenesis in xenograft models through down-regulation of vascular endothelial growth factor A (VEGFA) and hypoxia inducible factor 1 alpha (HIF1α) in tumor cells and chemokine (C-X-C motif) ligand 12 (CXCL12) in host stroma by immunohistochemical staining. Next, we investigated how HIF1α/VEGFA was down-regulated and how the reduction of CXCL12 inhibited tumor angiogenesis. We found that VEGFA secretion from endometrial cancer cells was decreased by Pro-EGCG treatment through inhibiting PI3K/AKT/mTOR/HIF1α pathway. Furthermore, the down-regulation of CXCL12 in stromal cells by Pro-EGCG treatment restricted migration and differentiation of macrophages thereby inhibited infiltration of VEGFA-expressing tumor-associated macrophages (TAMs). Taken together, we demonstrated that treatment with Pro-EGCG not only decreases cancer cell-secreted VEGFA but also inhibits TAM-secreted VEGFA in endometrial cancer. These findings demonstrate that Pro-EGCG is a novel angiogenesis inhibitor for endometrial cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective effect of epigallocatechin-3-gallate (EGCG) via Nrf2 pathway against oxalate-induced epithelial mesenchymal transition (EMT) of renal tubular cells.

PubMed

Kanlaya, Rattiyaporn; Khamchun, Supaporn; Kapincharanon, Chompunoot; Thongboonkerd, Visith

2016-07-25

This study evaluated effect of oxalate on epithelial mesenchymal transition (EMT) and potential anti-fibrotic property of epigallocatechin-3-gallate (EGCG). MDCK renal tubular cells were incubated with 0.5 mM sodium oxalate for 24-h with/without 1-h pretreatment with 25 μM EGCG. Microscopic examination, immunoblotting and immunofluorescence staining revealed that oxalate-treated cells gained mesenchymal phenotypes by fibroblast-like morphological change and increasing expression of vimentin and fibronectin, while levels of epithelial markers (E-cadherin, occludin, cytokeratin and ZO-1) were decreased. EGCG pretreatment could prevent all these changes and molecular mechanisms underlying the prevention by EGCG were most likely due to reduced production of intracellular ROS through activation of Nrf2 signaling and increased catalase anti-oxidant enzyme. Knockdown of Nrf2 by small interfering RNA (siRNA) abrogated all the effects of EGCG, confirming that the EGCG protection against oxalate-induced EMT was mediated via Nrf2. Taken together, our data indicate that oxalate turned on EMT of renal tubular cells that could be prevented by EGCG via Nrf2 pathway. These findings also shed light onto development of novel therapeutics or preventive strategies of renal fibrosis in the future.

Biopharmaceutical evaluation of epigallocatechin gallate-loaded cationic lipid nanoparticles (EGCG-LNs): In vivo, in vitro and ex vivo studies.

PubMed

Fangueiro, Joana F; Calpena, Ana C; Clares, Beatriz; Andreani, Tatiana; Egea, Maria A; Veiga, Francisco J; Garcia, Maria L; Silva, Amélia M; Souto, Eliana B

2016-04-11

Cationic lipid nanoparticles (LNs) have been tested for sustained release and site-specific targeting of epigallocatechin gallate (EGCG), a potential polyphenol with improved pharmacological profile for the treatment of ocular pathologies, such as age-related macular edema, diabetic retinopathy, and inflammatory disorders. Cationic EGCG-LNs were produced by double-emulsion technique; the in vitro release study was performed in a dialysis bag, followed by the drug assay using a previously validated RP-HPLC method. In vitro HET-CAM study was carried out using chicken embryos to determine the potential risk of irritation of the developed formulations. Ex vivo permeation profile was assessed using rabbit cornea and sclera isolated and mounted in Franz diffusion cells. The results show that the use of cationic LNs provides a prolonged EGCG release, following a Boltzmann sigmoidal profile. In addition, EGCG was successfully quantified in both tested ocular tissues, demonstrating the ability of these formulations to reach both anterior and posterior segment of the eye. The pharmacokinetic study of the corneal permeation showed a first order kinetics for both cationic formulations, while EGCG-cetyltrimethylammonium bromide (CTAB) LNs followed a Boltzmann sigmoidal profile and EGCG-dimethyldioctadecylammonium bromide (DDAB) LNs a first order profile. Our studies also proved the safety and non-irritant nature of the developed LNs. Thus, loading EGCG in cationic LNs is recognised as a promising strategy for the treatment of ocular diseases related to anti-oxidant and anti-inflammatory pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin.

PubMed

Dyer, Paul D R; Kotha, Arun K; Gollings, Alex S; Shorter, Susan A; Shepherd, Thomas R; Pettit, Marie W; Alexander, Bruce D; Getti, Giulia T M; El-Daher, Samer; Baillie, Les; Richardson, Simon C W

2016-07-01

The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC(50) for RT was 0.08±0.004 ng/mL whereas the IC(50) for RT+100 μM eGCG was 3.02±0.572 ng/mL, indicating that eGCG mediated a significant (p<0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC(50) values were obtained for RT (0.54±0.024 ng/mL) and RT+100 μM eGCG (0.68±0.235 ng/mL) again using 100 μM eGCG and was significant (p=0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100 μg/mL (i.e. 178 and 223 μM respectively) of eGCG mediating a significant (p=0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4 ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10 ng/mL and 5 ng/mL of RT was used. The addition of 1000 μM and 100 μM eGCG mediated a significant (p=0.0015 and <0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1 μg eGCG. Further, eGCG (100 μM) was found to reduce the binding of RT B chain to lactose-conjugated Sepharose as well as significantly (p=0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes via Inhibition of JAK2: Its Implication for Vitiligo Treatment.

PubMed

Ning, Weixuan; Wang, Suiquan; Dong, Xiaowu; Liu, Dongyin; Fu, Lifang; Jin, Rong; Xu, Aie

2015-01-01

Vitiligo is an inflammatory skin disorder in which activated T cells play an important role in its onset and progression. Epigallocatechin-3-gallate (EGCG), the major chemical constituent of green tea, exhibits remarkable anti-oxidative and anti-inflammatory properties. EGCG administration has been confirmed to decrease the risk of vitiligo; however, the underlying mechanism is undetermined. In this study, we proved that EGCG directly inhibited the kinase activity of Janus kinase 2 (JAK2). In primary cultured human melanocytes, EGCG pre-treatment attenuated interferon (IFN)-γ-induced phosphorylation of JAK2 and its downstream signal transducer and activator of transcription (STAT)1 and STAT3 in a dose-dependent manner. We further examined the chemoattractant expression in melanocytes and demonstrated that EGCG significantly inhibited IFN-γ-induced expression of intracellular adhesion molecule (ICAM)-1, CXCL10, and monocyte chemotactic protein (MCP)-1 in human melanocytes. In addition, EGCG reduced the protein levels of the corresponding receptors including CD11a, CXCR3, and CCR2 in human T lymphocytes. As a consequence, adhesion of human T cells to melanocytes induced by IFN-γ was effectively suppressed by EGCG. Taken together, our results provided new evidence for the effectiveness of EGCG in vitiligo treatment and supported JAK2 as a molecular target for vitiligo medicine development.

Reduction in Autophagy by (-)-Epigallocatechin-3-Gallate (EGCG): a Potential Mechanism of Prevention of Mitochondrial Dysfunction After Subarachnoid Hemorrhage.

PubMed

Chen, Ying; Huang, Liyong; Zhang, Huiyong; Diao, Xiling; Zhao, Shuyang; Zhou, Wenke

2017-01-01

Mitochondrial dysfunction and subsequent autophagy, which are common features in central nervous system (CNS) disorders, were found to contribute to neuronal cell injury after subarachnoid hemorrhage (SAH). (-)-Epigallocatechin-3-gallate (EGCG), the main biological active of tea catechin, is well known for its beneficial effects in the treatment of CNS diseases. Here, the ability of EGCG to rescue cellular injury and mitochondrial function following the improvement of autophagic flux after SAH was investigated. As expected, EGCG-protected mitochondrial function depended on the inhibition of cytosolic Ca 2+ concentration ([Ca 2+ ] i ) influx via voltage-gated calcium channels (VGCCs) and, consequently, mitochondrial Ca 2+ concentration ([Ca 2+ ] m ) overload via mitochondrial Ca 2+ uniporter (MCU). The attenuated [Ca 2+ ] i and [Ca 2+ ] m levels observed in the EGCG-treated group likely lessened oxyhemoglobin (OxyHb)-induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization, mitochondrial membrane permeability transition pore (mPTP) opening, reactive oxygen species (ROS), and cytochrosome c (cyt c) releasing. Subsequently, EGCG can restore the disrupted autophagy flux after SAH both at the initiation and formation stages by regulating Atg5, LC3B, and Becn-1 (Beclin-1) mRNA expressions. Thus, precondition EGCG resulted in autophagosomes and more autolysosomes compared with SAH group. As a result, EGCG pre-treatment increased the neurological score and decreased cell death. This study suggested that the mitochondrial dysfunction and abnormal autophagy flux synergistically contribute to SAH pathogenesis. Thus, EGCG can be regarded as a new pharmacological agent that targets both mitochondria and altered autophagy in SAH therapy.

[The effect of epigallocatechin gallate (EGCG) on the surface properties of nickel-chromium dental casting alloys after electrochemical corrosion].

PubMed

Qiao, Guang-yan; Zhang, Li-xia; Wang, Jue; Shen, Qing-ping; Su, Jian-sheng

2014-08-01

To investigate the effect of epigallocatechin gallate (EGCG) on the surface properties of nickel-chromium dental alloys after electrochemical corrosion. The surface morphology and surface structure of nickel-chromium dental alloys were examined by stereomicroscope and scanning electron microscopy before and after electrochemical tests in 0 g/L and 1.0 g/L EGCG artificial saliva. The surface element component and chemical states of nickel-chromium dental alloys were analyzed by X-ray photoelectron spectrograph after electrochemical tests in 0 g/L and 1.0 g/L EGCG artificial saliva. More serious corrosion happened on the surface of nickel-chromium alloy in 1.0 g/L EGCG artificial saliva than in 0 g/L EGCG. The diameters of corrosion pits were smaller, and the dendrite structure of the alloy surface was not affected in 0 g/L EGCG. While the diameters of corrosion pits were larger, the dendritic interval of the alloy surface began to merge, and the dendrite structure was fuzzy in 1.0 g/L EGCG. In addition, the O, Ni, Cr, Be, C and Mo elements were detected on the surface of nickel-chromium alloys after sputtered for 120 s in 0 g/L EGCG and 1.0 g/L EGCG artificial saliva after electrochemical corrosion, and the surface oxides were mainly NiO and Cr(2)O(3). Compared with 0 g/L EGCG artificial saliva, the content of O, NiO and Cr(2)O(3) were lower in 1.0 g/L EGCG. The results of surface morphology and the corrosion products both show that the corrosion resistance of nickel-chromium alloys become worse and the oxide content of corrosion products on the surface reduce in 1.0 g/L EGCG artificial saliva.

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: a potential role for reducing UVB light-induced retinal damage.

PubMed

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin; Yan, Biao

2013-09-06

Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy. Published by Elsevier Inc.

The activity of catechol-O-methyltransferase (COMT) is not impaired by high doses of epigallocatechin-3-gallate (EGCG) in vivo.

PubMed

Lorenz, Mario; Paul, Friedemann; Moobed, Minoo; Baumann, Gert; Zimmermann, Benno F; Stangl, Karl; Stangl, Verena

2014-10-05

Catechol-O-methyltransferase (COMT) inactivates many endogenous and exogenous compounds by O-methylation. Therefore, it represents a major enzyme of the metabolic pathway with important biological functions in hormonal and drug metabolism. The tea catechin epigallocatechin-3-gallate (EGCG) is known to inhibit COMT enzymatic activity in vitro. Based on beneficial in vitro results, EGCG is extensively used in human intervention studies in a variety of human diseases. Owing to its low bioavailability, rather high doses of EGCG are frequently applied that may impair COMT activity in vivo. Enzymatic activities of four functional COMT single-nucleotide polymorphisms (SNPs) were determined in red blood cells (RBCs) in 24 healthy human volunteers (14 women, 10 men). The subjects were supplemented with 750 mg of EGCG and EGCG plasma levels and COMT enzyme activities in erythrocytes were measured before and 2 h after intervention. The homozygous Val→Met substitution in the SNP rs4680 resulted in significantly decreased COMT activity. Enzymatic COMT activities in RBCs were also affected by the other three COMT polymorphisms. EGCG plasma levels significantly increased after intervention. They were not influenced by any of the COMT SNPs and different enzyme activities. Ingestion of 750 mg EGCG did not result in impairment of COMT activity. However, COMT activity was significantly increased by 24% after EGCG consumption. These results indicate that supplementation with a high dose of EGCG does not impair the activity of COMT. Consequently, it may not interfere with COMT-mediated metabolism and elimination of exogenous and endogenous COMT substrates. Copyright © 2014 Elsevier B.V. All rights reserved.

Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy

PubMed Central

Granja, Andreia; Pinheiro, Marina; Reis, Salette

2016-01-01

Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (−)-Epigallocatechin-3-gallate (EGCG) is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG’s properties and potentiate its anti-tumoral activity. PMID:27213442

Phase I study of topical epigallocatechin-3-gallate (EGCG) in patients with breast cancer receiving adjuvant radiotherapy.

PubMed

Zhao, Hanxi; Zhu, Wanqi; Jia, Li; Sun, Xiaorong; Chen, Guanxuan; Zhao, Xianguang; Li, Xiaolin; Meng, Xiangjiao; Kong, Lingling; Xing, Ligang; Yu, Jinming

2016-01-01

The purpose of this study was to investigate the safety, tolerability and preliminary effectiveness of topical epigallocatechin-3-gallate (EGCG) for radiation dermatitis in patients with breast cancer receiving adjuvant radiotherapy. Patients with breast cancer who received radiotherapy to the chest wall after mastectomy were enrolled. EGCG solution was sprayed to the radiation field from the initiation of Grade 1 radiation dermatitis until 2 weeks after completion of radiotherapy. EGCG concentration escalated from 40 to 660 μmol l(-1) in 7 levels with 3-6 patients in each level. EGCG toxicity was graded using the NCI (National Cancer Institute Common Terminology Criteria for Adverse Events) v. 3.0. Any adverse event >Grade 1 attributed to EGCG was considered dose-limiting toxicity. The maximum tolerated dose was defined as the dose level that induced dose-limiting toxicity in more than one-third of patients at a given cohort. Radiation dermatitis was recorded weekly by the Radiation Therapy Oncology Group scoring and patient-reported symptoms. From March 2012 to August 2013, 24 patients were enrolled. Acute skin redness was observed in 1 patient and considered to be associated with the EGCG treatment at 140 μmol l(-1) level. Three more patients were enrolled at this level and did not experience toxicity to EGCG. The dose escalation stopped at 660 μmol l(-1). No other reported acute toxicity was associated with EGCG. Grade 2 radiation dermatitis was observed in eight patients during or after radiotherapy, but all decreased to Grade 1 after EGCG treatments. Patient-reported symptom scores were significantly decreased at 2 weeks after the end of radiotherapy in pain, burning, itching and tenderness, p < 0.05. The topical administration of EGCG was well tolerated and the maximum tolerated dose was not found. EGCG may be effective in treating radiation dermatitis with preliminary investigation. EGCG solution seemed to be feasible for treating

Y-27632 Increases Sensitivity of PANC-1 Cells to Epigallocatechin Gallate (EGCG) in Regulating Cell Proliferation and Migration

PubMed Central

Liu, Xing; Bi, Yongyi

2016-01-01

Background The study aimed to investigate the inhibitory effect of (1R,4r)-4-((R)-1-aminoethyl)-N-(pyridin-4-yl) cyclohexanecarboxamide (Y-27632) and (−)-epigallocatechin-3-gallate (EGCG) on the proliferation and migration of PANC-1 cells. EGCG, found in green tea, has been previously shown to be one of the most abundant and powerful catechins in cancer prevention and treatment. Y-27632, a selective inhibitor of rho-associated protein kinase 1, is widely used in treating cardiovascular disease, inflammation, and cancer. Material/Methods PANC-1 cells, maintained in Dulbecco’s Modified Eagle’s Medium, were treated with dimethyl sulfoxide (control) as well as different concentrations (20, 40, 60, and 80 μg/mL) of EGCG for 48 h. In addition, PANC-1 cells were treated separately with 60 μg/mL EGCG, 20 μM Y-27632, and EGCG combined with Y-27632 (60 μg/mL EGCG + 20 μM Y-27632) for 48 h. The effect of EGCG and Y-27632 on the proliferation and migration of PANC-1 cells was evaluated using Cell Counting Kit-8 and transwell migration assays. The expression of peroxisome proliferator–activated receptor alpha (PPARα) and Caspase-3 mRNA was determined by Quantitative real-time polymerase chain reaction (RT-qPCR). Results EGCG (20–80 μg/mL) inhibited cell viability in a dose-dependent manner. Y-27632 enhanced the sensitivity of PANC-1 cells to EGCG (by increasing the expression of PPARα and Caspase-3 mRNA) and suppressed cell proliferation. PANC-1 cell migration was inhibited by treatment with a combination of EGCG and Y-27632. Conclusions Y-27632 increases the sensitivity of PANC-1 cells to EGCG in regulating cell proliferation and migration, which is likely to be related to the expression of PPARα mRNA and Caspase-3 mRNA. PMID:27694793

The involvement of Nrf2 in the protective effects of (-)-Epigallocatechin-3-gallate (EGCG) on NaAsO2-induced hepatotoxicity.

PubMed

Han, Xiao-Dong; Zhang, Yan-Yan; Wang, Ke-Lei; Huang, Yong-Pan; Yang, Zhong-Bao; Liu, Zhi

2017-09-12

Arsenic exposure produces hepatotoxicity. The common mechanism determining its toxicity is the generation of oxidative stress. Oxidative stress induced by arsenic leads to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. (-)-Epigallocatechin-3-gallate (EGCG) possesses a potent antioxidant capacity and exhibits extensive pharmacological activities. This study aims to evaluate effects of EGCG on arsenic-induced hepatotoxicity and activation of Nrf2 pathway. Plasma activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were measured; Histological analyses were conducted to observe morphological changes; Biochemical indexes such as oxidative stress (Catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), reactive oxygen species (ROS)), Nrf2 signaling related genes ( Nrf2, Nqo1, and Ho-1 ) were assessed. The results showed that EGCG inhibited arsenic-induced hepatic pathological damage, liver ROS level and MDA level. Arsenic decreases the antioxidant enzymes SOD, GPX, and CAT activity and the decrease was inhibited by treatment of EGCG. Furthermore, EGCG attenuated the retention of arsenic in liver tissues and improved the expressions of Nrf2 signaling related genes ( Nrf2, Nqo1, and Ho-1 ). These findings provide evidences that EGCG may be useful for reducing hepatotoxicity associated with oxidative stress by the activation of Nrf2 signaling pathway. Our findings suggest a possible mechanism of antioxidant EGCG in preventing hepatotoxicity, which implicate that EGCG may be a potential treatment for arsenicosis therapy.

Effects of (-)-epigallocatechin gallate (EGCG) on DNA strand breaks as evaluated by single-cell gel electrophoresis (SCG) in human lymphocytes.

PubMed

Yuquan, L; Takeshita, T; Morimoto, K

2001-01-01

(-)-Epigallocatechin gallate (EGCG), a catechin polyphenol component, is the main ingredient of green tea extract. Although the anti-carcinogenic and cancer inhibitory effects of EGCG have been widely reported, its genotoxicity is not clear and seldom reported. In this study, we examined the effects of EGCG on DNA strand breaks in the isolated lymphocytes and whole blood lymphocytes obtained from two smoking subjects and a nonsmoking healthy subject using a single cell gel electrophoresis (SCG) assay. The results showed that after 2 hrs of treating the isolated lymphocytes from the smokers, EGCG induced a significant, increase in DNA strand breaks at concentrations from 2.5×10(-5) M to 2.0×10(-4) M, while after 2 hrs of treating the whole blood obtained from the same smokers, EGCG suppressed the DNA strand breaks in the lymphocytes at concentrations of 1.0×10(-4) M and 2.0×10(-4) M. A similar suppressive result was also shown in the whole blood lymphocytes from the nonsmoker at nearly the same concentrations, while at concentrations of 1.0×10(-3) M or 2.0×10(-3) M, EGCG induced a significant increase in DNA strand breaks in the whole blood lymphocytes from the nonsmoker. This result suggests that EGCG is not only inhibitory against DNA strand breaks in whole blood, but also genotoxic to the isolated or whole blood lymphocytes at high concentrations. Thus, more research is needed to comprehensively assess the effects of EGCG on genetic materials.

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu

Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD.more » Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy.« less

Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress.

PubMed

Holczer, Marianna; Besze, Boglárka; Zámbó, Veronika; Csala, Miklós; Bánhegyi, Gábor; Kapuy, Orsolya

2018-01-01

The maintenance of cellular homeostasis is largely dependent on the ability of cells to give an adequate response to various internal and external stimuli. We have recently proposed that the life-and-death decision in endoplasmic reticulum (ER) stress response is defined by a crosstalk between autophagy, apoptosis, and mTOR-AMPK pathways, where the transient switch from autophagy-dependent survival to apoptotic cell death is controlled by GADD34. The aim of the present study was to investigate the role of epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, in promoting autophagy-dependent survival and to verify the key role in connecting GADD34 with mTOR-AMPK pathways upon prolonged ER stress. Our findings, obtained by using HEK293T cells, revealed that EGCG treatment is able to extend cell viability by inducing autophagy. We confirmed that EGCG-induced autophagy is mTOR-dependent and PKA-independent; furthermore, it also required ULK1. We show that pretreatment of cells with EGCG diminishes the negative effect of GADD34 inhibition (by guanabenz or siGADD34 treatment) on autophagy. EGCG was able to delay apoptotic cell death by upregulating autophagy-dependent survival even in the absence of GADD34. Our data suggest a novel role for EGCG in promoting cell survival via shifting the balance of mTOR-AMPK pathways in ER stress.

Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress

PubMed Central

Holczer, Marianna; Besze, Boglárka; Zámbó, Veronika

2018-01-01

The maintenance of cellular homeostasis is largely dependent on the ability of cells to give an adequate response to various internal and external stimuli. We have recently proposed that the life-and-death decision in endoplasmic reticulum (ER) stress response is defined by a crosstalk between autophagy, apoptosis, and mTOR-AMPK pathways, where the transient switch from autophagy-dependent survival to apoptotic cell death is controlled by GADD34. The aim of the present study was to investigate the role of epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, in promoting autophagy-dependent survival and to verify the key role in connecting GADD34 with mTOR-AMPK pathways upon prolonged ER stress. Our findings, obtained by using HEK293T cells, revealed that EGCG treatment is able to extend cell viability by inducing autophagy. We confirmed that EGCG-induced autophagy is mTOR-dependent and PKA-independent; furthermore, it also required ULK1. We show that pretreatment of cells with EGCG diminishes the negative effect of GADD34 inhibition (by guanabenz or siGADD34 treatment) on autophagy. EGCG was able to delay apoptotic cell death by upregulating autophagy-dependent survival even in the absence of GADD34. Our data suggest a novel role for EGCG in promoting cell survival via shifting the balance of mTOR-AMPK pathways in ER stress. PMID:29636854

Green-Tea and Epigallocatechin-3-Gallate are Bactericidal against Bacillus anthracis

DTIC Science & Technology

2017-06-13

EGCG, catechins such 245 as epigallocatechin and epicatechin gallate are also antibacterial agents. Moreover, the 246 bactericidal activity of green...Sharma A, Gupta S, Sarethy IP, Dang S, Gabrani R. 2012. Green tea extract: possible mechanism 285 and antibacterial activity on skin pathogens. Food...was shown to be responsible for this activity , against 30 both the attenuated B. anthracis ANR and the virulent, encapsulated strain B. anthracis

Fabrication of coated bovine serum albumin (BSA)-epigallocatechin gallate (EGCG) nanoparticles and their transport across monolayers of human intestinal epithelial Caco-2 cells.

PubMed

Li, Zheng; Ha, Jungheun; Zou, Tao; Gu, Liwei

2014-06-01

The bovine serum albumin (BSA)-epigallocatechin gallate (EGCG) nanoparticles were fabricated using a desolvation method, and coated with poly-ε-lysine or chitosan. BSA-EGCG nanoparticles (BEN), poly-ε-lysine coated BSA-EGCG nanoparticles (PBEN), and chitosan coated BSA-EGCG nanoparticles (CBEN) had a spherical morphology and a size of 186, 259, and 300 nm, respectively. The loading efficiency of EGCG in these nanoparticles was 32.3%, 35.4%, and 32.7%, whereas the loading capacity was 18.9%, 17.0%, and 16.0% (w/w), respectively. Poly-ε-lysine or chitosan coating prevented the aggregation of nanoparticles at pH 4.5-5.0. However, they caused particle aggregation at pH 6.5-7.0. BEN had negative zeta-potentials between pH 4.5 and 6.0. Poly-ε-lysine or chitosan coating changed the zeta-potentials to positive. The release study of EGCG from the nanoparticles in the simulated gastric or intestinal fluid with or without digestive enzymes showed that poly-ε-lysine and chitosan coatings delayed EGCG release from the nanoparticles. Poly-ε-lysine or chitosan coating improved the stability of EGCG during storage at 60 °C compared with EGCG in the uncoated particles. EGCG in BEN, PBEN, and CBEN had a decreasing apparent permeability coefficient (Papp) on Caco-2 monolayers, whereas pure EGCG showed relatively stable Papp during the incubation over time. EGCG in CBEN showed significantly higher Papp, suggesting that chitosan coated BSA-EGCG nanoparticles may improve the absorption of EGCG.

Anti-cancer effect of (-)-epigallocatechin-3-gallate (EGCG) in head and neck cancer through repression of transactivation and enhanced degradation of β-catenin.

PubMed

Shin, Yoo Seob; Kang, Sung Un; Park, Ju Kyeong; Kim, Yang Eun; Kim, Yeon Soo; Baek, Seung Joon; Lee, Seong-Ho; Kim, Chul-Ho

2016-11-15

Aberrant expression of β-catenin is highly associated with progression of various cancers including head and neck cancer (HNC). Green tea is most commonly used beverage in the world and one of the more bioactive compounds is the antioxidant epigallocatechin gallate (EGCG). This study was performed to investigate the mechanism by which EGCG inhibits the growth of HNC, focusing on the modulation of the expression and activity of β-catenin. In vitro effects of EGCG on the transcription, translation, or degradation of β-catenin were investigated. Antitumor effects of EGCG in vivo were evaluated in a syngeneic mouse model and β-catenin expression was checked in HNC patients' samples. β-catenin expression was elevated in tumor samples of HNC patients. EGCG induced apoptosis in KB and FaDu cells through the suppression of β-catenin signaling. Knockdown of β-catenin using siRNA enhanced the proapoptotic activities of EGCG. EGCG decreased mRNA and transcriptional activity of β-catenin in p53 wild-type KB cells. EGCG also enhanced the ubiquitination and proteasomal degradation of β-catenin. The suppression of β-catenin and consequent apoptosis were observed in response to EGCG treatment in a syngeneic mouse model. In conclusion, we report that EGCG inhibits β-catenin expression through multiple mechanisms including decreased transcription and increased ubiquitin-mediated 26S proteasomal degradation. This study proposes a novel molecular rationale for antitumor activities of green tea in HNCs. Copyright © 2016 Elsevier GmbH. All rights reserved.

Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains

PubMed Central

Hora, Manuel; Carballo-Pacheco, Martin; Weber, Benedikt; Morris, Vanessa K.; Wittkopf, Antje; Buchner, Johannes; Strodel, Birgit; Reif, Bernd

2017-01-01

Antibody light chain amyloidosis is a rare disease caused by fibril formation of secreted immunoglobulin light chains (LCs). The huge variety of antibody sequences puts a serious challenge to drug discovery. The green tea polyphenol epigallocatechin-3-gallate (EGCG) is known to interfere with fibril formation in general. Here we present solution- and solid-state NMR studies as well as MD simulations to characterise the interaction of EGCG with LC variable domains. We identified two distinct EGCG binding sites, both of which include a proline as an important recognition element. The binding sites were confirmed by site-directed mutagenesis and solid-state NMR analysis. The EGCG-induced protein complexes are unstructured. We propose a general mechanistic model for EGCG binding to a conserved site in LCs. We find that EGCG reacts selectively with amyloidogenic mutants. This makes this compound a promising lead structure, that can handle the immense sequence variability of antibody LCs. PMID:28128355

Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway.

PubMed

Yu, Chenxiao; Jiao, Yang; Xue, Jiao; Zhang, Qi; Yang, Hongying; Xing, Ligang; Chen, Guangxia; Wu, Jinchang; Zhang, Shuyu; Zhu, Wei; Cao, Jianping

2017-01-01

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, is widely studied as a cancer chemopreventive agent with potential anti-cancer effects. The NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is considered to mediate cellular resistance to EGCG. Metformin, a classical antidiabetic drug, has been shown to prevent cancer progression. Researchers have not reported whether metformin potentiates the anti-cancer efficacy of EGCG. In this study, metformin inhibited HO-1 expression and augmented the anti-tumor effect of EGCG. Metformin also enhanced ROS (reactive oxygen species) generation induced by EGCG (100 μM), subsequently resulting in apoptosis. Based on the results of the in vivo study, size of xenografts treated with the combination of metformin and EGCG was smaller than other groups. Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2. Moreover, metformin upregulated SIRT1 expression partially through the NF-kB pathway. Comparatively, the combination of EGCG and metformin showed little impact on normal lung epithelial BEAS-2B cells. Based on our findings, metformin sensitized NSCLC cells to the EGCG treatment by suppressing the Nrf2/HO-1 signaling pathway.

(-)-Epigallocatechin-3-gallate (EGCG) modulates neurological function when intravenously infused in acute and, chronically injured spinal cord of adult rats.

PubMed

Renno, Waleed M; Al-Khaledi, Ghanim; Mousa, Alyaa; Karam, Shaima M; Abul, Habib; Asfar, Sami

2014-02-01

Spinal cord injury (SCI) causes severe and long lasting motor and sensory deficits, chronic pain, and autonomic dysreflexia. (-)-epigallocatechin-3-gallate (EGCG) has shown to produce neuroprotective effect in a broad range of neurodegenerative disease animal models. This study designed to test the efficacy of intravenous infusion of EGCG for 36 h, in acutely injured rats' spinal cord: within first 4 h post-injury and, in chronically SC injured rats: after one year of injury. Functional outcomes measured using standard BBB scale, The Louisville Swim Scale (LSS) and, pain behavior assessment tests. 72 Female adult rats subjected to moderate thoracic SCI using MASCIS Impactor, blindly randomized as the following: (I) Acute SCI + EGCG (II) Acute SCI + saline. (III) Chronic SCI + EGCG. (IV) Chronic SCI + saline and, sham SCI animals. EGCG i.v. treatment of acute and, chronic SCI animals resulted in significantly better recovery of motor and sensory functions, BBB and LSS (P < 0.005) and (P < 0.05) respectively. Tactile allodynia, mechanical nociception (P < 0.05) significantly improved. Paw withdrawal and, tail flick latencies increase significantly (P < 0.05). Moreover, in the EGCG treated acute SCI animals the percentage of lesion size area significantly reduced (P < 0.0001) and, the number of neurons in the spinal cord increased (P < 0.001). Percent areas of GAP-43 and GFAP immunohistochemistry showed significant (P < 0.05) increase. We conclude that the therapeutic window of opportunity for EGCG to depict neurological recovery in SCI animals, is viable up to one year post SCI when intravenously infused for 36 h. Copyright © 2013 Elsevier Ltd. All rights reserved.

Transdermal solid delivery of epigallocatechin-3-gallate using self-double-emulsifying drug delivery system as vehicle: Formulation, evaluation and vesicle-skin interaction.

PubMed

Hu, Caibiao; Gu, Chengyu; Fang, Qiao; Wang, Qiang; Xia, Qiang

2016-02-01

The present study investigated a self-double-emulsifying drug delivery system loaded with epigallocatechin-3-gallate to improve epigallocatechin-3-gallate skin retention. The long chain solid lipids (cetostearyl alcohol) and macadamia oil were utilized as a carrier to deliver the bioactive ingredient. Response surface methodology was used to optimize the formulation, and the solid lipid to total lipid weight ratio, concentration of epigallocatechin-3-gallate and hydrophilic surfactant on skin retention were found to be the principal factors. The optimum formulation with high encapsulation efficiency (95.75%), self-double-emulsification performance (99.58%) and skin retention (87.24%) were derived from the fitted models and experimentally examined, demonstrating a reasonable agreement between experimental and predicted values. Epigallocatechin-3-gallate-self-double-emulsifying drug delivery system was found to be stable for 3 months. Transdermal studies could explain a higher skin diffusion of epigallocatechin-3-gallate from the self-double-emulsifying drug delivery system compared with EGCG aqueous solution. In vitro cytotoxicity showed that epigallocatechin-3-gallate-self-double-emulsifying drug delivery system did not exert hazardous effect on L929 cells up to 1:10. © The Author(s) 2015.

Fabrication of self-assembled (-)-epigallocatechin gallate (EGCG) ovalbumin-dextran conjugate nanoparticles and their transport across monolayers of human intestinal epithelial Caco-2 cells.

PubMed

Li, Zheng; Gu, Liwei

2014-02-12

Nanoparticles have the potential to increase bioavailability of nutraceutical compounds such as (-)-epigallocatechin gallate (EGCG). Ovalbumin was conjugated with dextran using the Maillard reaction. The resultant ovalbumin-dextran (O-D) conjugates were self-assembled with EGCG to form EGCG O-D conjugate nanoparticles at pH 5.2 after heating at 80 °C for 60 min. Ovalbumin in EGCG O-D conjugate nanoparticles was further cross-linked by glutaraldehyde for 24 h at room temperature. EGCG O-D conjugate nanoparticles and cross-linked EGCG O-D conjugate nanoparticles in aqueous suspension had particle sizes of 285 and 339 nm, respectively, and showed a spherical morphology. The loading efficiencies of EGCG in these two nanoparticles were 23.4 and 30.0%, whereas the loading capacities were 19.6 and 20.9%, respectively. These nanoparticles showed positive zeta-potentials in a pH range from 2.5 to 4.0 but had negative charges at pH ≥5.0. EGCG O-D conjugate nanoparticles maintained a particle size of 183-349 nm in simulated gastric fluid (SGF) and 188-291 nm in simulated intestinal fluid (SIF) at 37 °C for 2 h, whereas cross-linked nanoparticles had particle sizes of 294-527 nm in SGF and 206-300 nm in SIF. Limited release of EGCG was observed in both nanoparticle systems in simulated gastric and intestinal fluids without and with digestive enzymes. EGCG O-D conjugate nanoparticles significantly enhanced the apparent permeability coefficient (Papp) of EGCG on Caco-2 monolayers compared with EGCG solution, suggesting that these nanoparticles may improve the absorption of EGCG.

Preparation and characterization of (-)-Epigallocatechin-3-gallate (EGCG)-loaded nanoparticles and their inhibitory effects on Human breast cancer MCF-7 cells.

PubMed

Zeng, Liang; Yan, Jingna; Luo, Liyong; Ma, Mengjun; Zhu, Huiqun

2017-03-28

We were employing nanotechnology to improve the targeting ability of (-)-Epigallocatechin-3-gallate (EGCG) towards MCF-7 cells, and two kinds of EGCG nanoparticles (FA-NPS-PEG and FA-PEG-NPS) were obtained, besides, their characteristics and effects on MCF-7 cells were studied. The results indicated that (i) both FA-NPS-PEG and FA-PEG-NPS have high stabilities; (ii) their particles sizes were 185.0 ± 13.5 nm and 142.7 ± 7.2 nm, respectively; (iii) their encapsulation efficiencies of EGCG were 90.36 ± 2.20% and 39.79 ± 7.54%, respectively. (iv) there was no cytotoxicity observed in EGCG, FA-NPS-PEG and FA-PEG-NPS toward MCF-7 cells over all concentrations (0~400 μg/mL) tested; (v) EGCG, FA-NPS-PEG and FA-PEG-NPS inhibited MCF-7 cells proliferation in dose-dependent manners, with the average IC 50 of 470.5 ± 33.0, 65.9 ± 0.4 and 66.6 ± 0.6 μg/mL; (vi) EGCG, FA-NPS-PEG and FA-PEG-NPS could modulated the expressions of several key regulatory proteins in PI3K-Akt pathway such as up-regulation of PTEN, p21 and Bax, and down-regulation of p-PDK1, p-AKT, CyclinD1 and Bcl-2, which gave an illustration about the mechanism by which EGCG nanoparticles inhibited MCF-7 cells proliferation. In this study, EGCG nanoparticles can significantly enhance the targeting ability and efficacy of EGCG, which is considered to an experimental foundation for further research on its activity, targeting ability and metabolism in vivo.

An efflux pump (MexAB-OprM) of Pseudomonas aeruginosa is associated with antibacterial activity of Epigallocatechin-3-gallate (EGCG).

PubMed

Kanagaratnam, Rashmi; Sheikh, Rida; Alharbi, Fahad; Kwon, Dong H

2017-12-01

Pseudomonas aeruginosa is a notorious multidrug resistant nosocomial pathogen. An efflux pump (MexAB-OprM) is the main contributor to the multidrug resistance in clinical isolates of P. aeruginosa. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound extracted from green tea, exhibits antibacterial activity. It is unclear that molecular details of the antibacterial activity of EGCG, EGCG-effect on antibiotic susceptibility, and clinical relevance of EGCG in bacteria. This study aimed to determine the roles of the efflux pump and an efflux pump inhibitor (phenylalanine-arginine β-naphthylamide; PAβN) in the antibacterial activity of EGCG and the EGCG-effect on antibiotic susceptibility. Twenty-two multidrug resistant clinical isolates of P. aeruginosa and a wild type P. aeruginosa PAO1 were used to determine antibacterial activity of EGCG and EGCG-effect on antibiotic susceptibility. An efflux pump (MexAB-OPrM) mutant strain, its complemented strain carrying an intact mexAB-oprM, and their parental strain were used to determine roles of MexAB-OprM in the antibacterial activity of EGCG and EGCG-mediated antibiotic susceptibility. PAβN was also used to evaluate EGCG as a possible efflux pump inhibitor. EGCG inhibited cellular growth and killed 100% of cells at 64-512 µg/ml and at 256-1024 µg/ml, respectively, in all tested 22 clinical isolates including the wild type strain. A subinhibitory concentration of EGCG significantly enhanced susceptibility to antibiotics, unexceptionally to chloramphenicol and tetracyclines (≥4-fold) of the clinical isolates. Both the antibacterial activity of EGCG and the EGCG-mediated antibiotic susceptibility were enhanced more in the efflux pump mutant strain (mexB::Gm) than the parental strain, suggesting additionally accumulated-EGCG produced the more antibacterial activity in the mutant strain. EGCG was synergistically interacted with PAβN with enhancing susceptibility to all tested antibiotics (up to >500-fold) at

Epigallocatechin gallate (EGCG), influences a murine WEHI-3 leukemia model in vivo through enhancing phagocytosis of macrophages and populations of T- and B-cells.

PubMed

Huang, An-Cheng; Cheng, Hsiu-Yueh; Lin, Tsu-Shun; Chen, Wen-Hsein; Lin, Ju-Hwa; Lin, Jen-Jyh; Lu, Chi-Cheng; Chiang, Jo-Hua; Hsu, Shu-Chun; Wu, Ping-Ping; Huang, Yi-Ping; Chung, Jing-Gung

2013-01-01

Epigallocatechin gallate (EGCG) is the major polyphenol in green tea, and has been reported to have anticancer effects on many types of cancer cells. However, there is no report to show its effects on the immune response in a murine leukemia mouse model. Thus, in the present study, we investigated the effects of EGCG on the immune responses of murine WEHI-3 leukemia cells in vivo. WEHI-3 cells were intraperitoneally injected into normal BALB/c mice to establish leukemic BALB/c mice, which were then oral-treated with or without EGCG at 5, 20 and 40 mg/kg for two weeks. The results indicated that EGCG did not change the weight of the animals, nor the liver or spleen when compared to vehicle (olive oil) -treated groups. Furthermore, EGCG increased the percentage of cluster of differentiation 3 (CD3) (T-cell), cluster of differentiation 19 (CD19) (B-cell) and Macrophage-3 antigen (Mac-3) (macrophage) but reduced the percentage of CD11b (monocyte) cell surface markers in EGCG-treated groups as compared with the untreated leukemia group. EGCG promoted the phagocytosis of macrophages from 5 mg/kg treatment and promoted natural killer cell activity at 40 mg/kg, increased T-cell proliferation at 40 mg/kg but promoted B-cell proliferation at all three doses. Based on these observations, it appears that EGCG might exhibit an immune response in the murine WEHI-3 cell line-induced leukemia in vivo.

Cavernous antioxidant effect of green tea, epigallocatechin-3-gallate with/without sildenafil citrate intake in aged diabetic rats.

PubMed

Mostafa, T; Sabry, D; Abdelaal, A M; Mostafa, I; Taymour, M

2013-08-01

This study aimed to assess the cavernous antioxidant effect of green tea (GT), epigallocatechin-3-gallate (EGCG) with/without sildenafil citrate intake in aged diabetic rats. One hundred and four aged male white albino rat were divided into controls that received ordinary chow, streptozotocin (STZ)-induced aged diabetic rats, STZ-induced diabetic rats on infused green tea, induced diabetic rats on epigallocatechin-3-gallate and STZ-induced diabetic rats on sildenafil citrate added to EGCG. After 8 weeks, dissected cavernous tissues were assessed for gene expression of eNOS, cavernous malondialdehyde (MDA), glutathione peroxidase (GPx), cyclic guanosine monophosphate (cGMP), and serum testosterone (T). STZ-induced diabetic rats on GT demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats. Diabetic rats on EGCG demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats or diabetic rats on GT. Diabetic rats on EGCG added to sildenafil showed significant increase in cavernous eNOS, cGMP and significant decrease in cavernous MDA compared with other groups. Serum T demonstrated nonsignificant difference between the investigated groups. It is concluded that GT and EGCG have significant cavernous antioxidant effects that are increased if sildenafil is added. © 2012 Blackwell Verlag GmbH.

Preparation and characterization of (−)-Epigallocatechin-3-gallate (EGCG)-loaded nanoparticles and their inhibitory effects on Human breast cancer MCF-7 cells

PubMed Central

Zeng, Liang; Yan, Jingna; Luo, Liyong; Ma, Mengjun; Zhu, Huiqun

2017-01-01

We were employing nanotechnology to improve the targeting ability of (−)-Epigallocatechin-3-gallate (EGCG) towards MCF-7 cells, and two kinds of EGCG nanoparticles (FA-NPS-PEG and FA-PEG-NPS) were obtained, besides, their characteristics and effects on MCF-7 cells were studied. The results indicated that (i) both FA-NPS-PEG and FA-PEG-NPS have high stabilities; (ii) their particles sizes were 185.0 ± 13.5 nm and 142.7 ± 7.2 nm, respectively; (iii) their encapsulation efficiencies of EGCG were 90.36 ± 2.20% and 39.79 ± 7.54%, respectively. (iv) there was no cytotoxicity observed in EGCG, FA-NPS-PEG and FA-PEG-NPS toward MCF-7 cells over all concentrations (0~400 μg/mL) tested; (v) EGCG, FA-NPS-PEG and FA-PEG-NPS inhibited MCF-7 cells proliferation in dose-dependent manners, with the average IC50 of 470.5 ± 33.0, 65.9 ± 0.4 and 66.6 ± 0.6 μg/mL; (vi) EGCG, FA-NPS-PEG and FA-PEG-NPS could modulated the expressions of several key regulatory proteins in PI3K-Akt pathway such as up-regulation of PTEN, p21 and Bax, and down-regulation of p-PDK1, p-AKT, CyclinD1 and Bcl-2, which gave an illustration about the mechanism by which EGCG nanoparticles inhibited MCF-7 cells proliferation. In this study, EGCG nanoparticles can significantly enhance the targeting ability and efficacy of EGCG, which is considered to an experimental foundation for further research on its activity, targeting ability and metabolism in vivo. PMID:28349962

Niosomes consisting of tween-60 and cholesterol improve the chemical stability and bioavailability of (-)-epigallocatechin gallate during gastrointestinal tract

USDA-ARS?s Scientific Manuscript database

(-)-Epigallocatechin gallate (EGCG), the major polyphenol in green tea, has been shown to protect against chronic diseases. The mechanisms have been attributed to interactions with cell signaling pathways and its antioxidant properties. In vivo studies are difficult because of its limited bioavail...

Modulation of hexavalent chromium-induced genotoxic damage in peripheral blood of mice by epigallocatechin-3-gallate (EGCG) and its relationship to the apoptotic activity.

PubMed

García-Rodríguez, María Del Carmen; Montaño-Rodríguez, Ana Rosa; Altamirano-Lozano, Mario Agustín

2016-01-01

This study was conducted to investigate the relationship between modulation of genotoxic damage and apoptotic activity in Hsd:ICR male mice treated with (-)-epigallocatechin-3-gallate (EGCG) and hexavalent chromium [Cr(VI)]. Four groups of 5 mice each were treated with (i) control vehicle only, (ii) EGCG (10 mg/kg) by gavage, (iii) Cr(VI) (20 mg/kg of CrO3) intraperitoneally (ip), and (iv) EGCG in addition to CrO3 (EGCG-CrO3). Genotoxic damage was evaluated by examining presence of micronucleated polychromatic erythrocytes (MN-PCE) obtained from peripheral blood of the caudal vein at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. EGCG treatment produced no significant changes in frequency of MN-PCE. However, CrO3 treatment significantly increased number of MN-PCE at 24 and 48 h post injection. Treatment with EGCG prior to CrO3 injection decreased number of MN-PCE compared to CrO3 alone. The MN-PCE reduction was greater than when EGCG was administered ip. The frequency of early apoptotic cells was elevated at 48 h following EGCG, CrO3, or EGCG-CrO3 exposure, with highest levels observed in the combined treatment group, while the frequencies of late apoptotic cells and necrotic cells were increased only in EGCG-CrO3 exposure. Our findings support the view that EGCG is protective against genotoxic damage induced by Cr(VI) and that apoptosis may contribute to elimination of DNA-damaged cells (MN-PCE) when EGCG was administered prior to CrO3. Further, it was found that the route of administration of EGCG plays an important role in protection against CrO3-induced genotoxic damage.

Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7.

PubMed

Sen, Triparna; Moulik, Shuvojit; Dutta, Anindita; Choudhury, Paromita Roy; Banerji, Aniruddha; Das, Shamik; Roy, Madhumita; Chatterjee, Amitava

2009-02-13

The tumor inhibiting property of green tea polyphenol epigallocatechin-3-gallate (EGCG) is well documented. Studies reveal that matrix-metalloproteinases (MMPs) play pivotal roles in tumor invasion through degradation of basement membranes and extracellular matrix (ECM). We studied the effect of EGCG on matrixmetalloproteinases-2 (MMP-2), the factors involved in activation, secretion and signaling molecules that might be involved in the regulation of MMP-2 in human breast cancer cell line, MCF-7. MCF-7 was treated with EGCG (20 muM, 24 h), the effect of EGCG on MMP-2 expression, activity and its regulatory molecules were studied by gelatin zymography, Western blot, quantitative and semi-quantitative real time RT-PCR, immunoflourescence and cell adhesion assay. EGCG treatment reduced the activity, protein expression and mRNA expression level of MMP-2. EGCG treatment reduced the expression of focal adhesion kinase (FAK), membrane type-1-matrix metalloproteinase (MT1-MMP), nuclear factor-kappa B (NF-kB), vascular endothelial growth factor (VEGF) and reduced the adhesion of MCF-7 cells to ECM, fibronectin and vitronectin. Real time RT-PCR revealed a reduced expression of integrin receptors alpha5, beta1, alphav and beta3 due to EGCG treatment. Down regulation of expression of MT1-MMP, NF-kB, VEGF and disruption of functional status of integrin receptors may indicate decreased MMP-2 activation; low levels of FAK expression might indicate disruption in FAK-induced MMP-2 secretion and decrease in activation of phosphatidyl-inositol-3-kinase (PI-3K), extracellular regulated kinase (ERK) indicates probable hindrance in MMP-2 regulation and induction. We propose EGCG as potential inhibitor of expression and activity of pro-MMP-2 by a process involving multiple regulatory molecules in MCF-7.

Bioactivity of Epigallocatechin Gallate Nanoemulsions Evaluated in Mice Model.

PubMed

Koutelidakis, Antonios E; Argyri, Konstantina; Sevastou, Zoi; Lamprinaki, Dimitra; Panagopoulou, Elli; Paximada, Evi; Sali, Aggeliki; Papalazarou, Vassilis; Mallouchos, Athanasios; Evageliou, Vasiliki; Kostourou, Vasiliki; Mantala, Ioanna; Kapsokefalou, Maria

2017-09-01

The hypothesis that incorporation of epigallocatechin gallate (EGCG) into nanoemulsions may increase its bioactivity compared with EGCG aqueous solutions was examined in mice. After an in vitro study in a model system with stimulated gastrointestinal conditions, the following EGCG nanoemulsions were used in a mice experiment: Emulsion I: emulsion water in oil (W/O), which contained 0.23 mg/mL EGCG in aqueous phase; Emulsion II: emulsion oil in water (O/W), which contained 10% olive oil and 0.23 mg/mL esterified EGCG in fatty phase; and Emulsion III: emulsion O/W in water (W1/O/W2; 8:32:60), which contained 32% olive oil and 0.23 mg/mL EGCG in aqueous phase. After 2 h of mice administration by gavage with 0.1 mL of EGCG nanoemulsions, total antioxidant capacity (TAC) of plasma and some tissues (especially colon, jejunum, heart, spleen) was measured with Ferric-Reducing Antioxidant Power (FRAP) and Oxygen Radical Absorbance Capacity (ORAC) assays. No toxic effects were observed after administration of 0.23 mg/mL esterified EGCG in CD1 mouse strain. The study concluded that administration of mice with the three EGCG nanoemulsions did not increase their TAC in specific tissues, compared with an aqueous EGCG solution at the same concentration. Nevertheless, the esterified EGCG emulsion (Emulsion II) exerted an increase in mice plasma compared with aqueous EGCG and showed higher values of TAC in several tissues, compared with Emulsions I and III. EGCG nanoemulsions could be considered a useful method in plethora functional food applications, but further research is required for safer results.

Effect of processing on physicochemical characteristics and bioefficacy of β-lactoglobulin-epigallocatechin-3-gallate complexes.

PubMed

Lestringant, Pauline; Guri, Anilda; Gülseren, Ibrahim; Relkin, Perla; Corredig, Milena

2014-08-20

Varying amounts of epigallocatechin-3-gallate (EGCG) were encapsulated in β-lactoglobulin (β-Lg) nanoparticles, either native or processed, denoted as heated or desolvated protein. The stability, physical properties, and bioactivity of the β-Lg-EGCG complexes were tested. Native β-Lg-EGCG complexes showed comparable stability and binding efficacy (EGCG/β-Lg molar ratio of 1:1) to heated β-Lg nanoparticles (1% and 5% protein w/w). The sizes of heated and desolvated β-Lg nanoparticles were comparable, but the latter showed the highest binding affinity for EGCG. The presence of EGCG complexed with β-Lg did not affect the interfacial tension of the protein when tested at the soy oil-water interface but caused a decrease in dilational elasticity. All β-Lg complexes (native, heated, or desolvated) showed a decrease in cellular proliferation similar to that of free ECGC. In summary, protein-EGCG complexes did not alter the bioefficacy of EGCG and contributed to increased stability with storage, demonstrating the potential benefits of nanoencapsulation.

Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release.

PubMed

Cao, Yizheng; Teng, Jing; Selbo, Jon

2017-11-09

Epigallocatechin gallate (EGCG) has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity) and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus ® 50:50 ( w / w ) shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma.

Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release

PubMed Central

Cao, Yizheng; Teng, Jing; Selbo, Jon

2017-01-01

Epigallocatechin gallate (EGCG) has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity) and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus® 50:50 (w/w) shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma. PMID:29120370

Scavenging of long-lived radicals by (-)-epigallocatechin-3- O-gallate and simultaneous suppression of mutation in irradiated mammalian cells

NASA Astrophysics Data System (ADS)

Kumagai, Jun; Nakama, Mitsuo; Miyazaki, Tetsuo; Ise, Tamaki; Kodama, Seiji; Watanabe, Masami

2002-07-01

Effect of (-)-epigallocatechin-3- O-gallate (EGCg) on scavenging long-lived radicals and its biological significance were investigated using electron-spin-resonance spectroscopy and mutation assay in cultured human embryo cells. EGCg scavenged long-lived radicals in irradiated golden hamster embryo cells and albumin solution, and simultaneously reduced mutation frequency in the irradiated human embryo cells. These results indicate that long-lived radials are involved in the induction of mutation by radiation.

GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea.

PubMed

Pi, Min; Kapoor, Karan; Ye, Ruisong; Smith, Jeremy C; Baudry, Jerome; Quarles, Leigh D

2018-04-01

The molecular mechanisms whereby gallates in green tea exert metabolic effects are poorly understood. We found that GPRC6A, a multi-ligand-sensing G-protein-coupled receptor that regulates energy metabolism, sex hormone production, and prostate cancer progression, is a target for gallates. Sodium gallate (SG), gallic acid (GA) > ethyl gallate (EG) > octyl gallate (OG) dose dependently activated ERK in HEK-293 cells transfected with GPRC6A but not in non-transfected controls. SG also stimulated insulin secretion in β-cells isolated from wild-type mice similar to the endogenous GPRC6A ligands, osteocalcin (Ocn) and testosterone (T). Side-chain additions to create OG resulted in loss of GPRC6A agonist activity. Another component of green tea, epigallocatechin 3-gallate (EGCG), dose-dependently inhibited Ocn activation of GPRC6A in HEK-293 cells transfected with GPRC6A and blocked the effect of Ocn in stimulating glucose production in CH10T1/2 cells. Using structural models of the venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A, calculations suggest that l-amino acids and GA bind to the VFT, whereas EGCG is calculated to bind to sites in both the VFT and 7-TM. GA and EGCG have offsetting agonist and antagonist effects on GPRC6A that may account for the variable metabolic effect of green tea consumption. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metagenomics Analysis of Gut Microbiota in a High Fat Diet-Induced Obesity Mouse Model Fed with (-)-Epigallocatechin 3-O-(3-O-Methyl) Gallate (EGCG3''Me).

PubMed

Zhang, Xin; Chen, Yuhui; Zhu, Jieyu; Zhang, Man; Ho, Chi-Tang; Huang, Qingrong; Cao, Jinxuan

2018-05-15

(-)-Epigallocatechin 3-O-(3-O-methyl) gallate (EGCG3''Me) has been shown to have a modulatory effect on human intestinal microbiota, and the relationship between intestinal flora and obesity has attracted more and more attention recently. Here, we investigated the potential link between EGCG3''Me and gut microbiota composition, as well as the underlying mechanisms of the anti-obesity activity of EGCG3''Me. EGCG3''Me was prepared from oolong tea by column chromatography, and the influence of EGCG3''Me on intestinal microbiota was analysed using a human flora-associated high fat diet (HFD)-induced obesity mouse model by metagenomics. EGCG3''Me showed a weight reducing effect, ameliorated the HFD-induced gut dysbiosis, and significantly decreased the ratio of Firmicutes/Bacteroidetes. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database provided significant differences in differentially expressed genes in response to EGCG3''Me treatment. The results showed enrichment of genes involved in the biosynthesis of amino acids, the two-component system, ATP-binding cassette (ABC) transporters, purine metabolism and carbon metabolism. An EGCG3''Me supplemented diet produces promising effects on gut micro-ecology by enhancing beneficial microbial populations and by affecting metabolic pathways including amino acids biosynthesis, the two-component system, and ABC transporters, contributing to the improvement of host health. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Epigallocatechin-3-gallate (EGCG) as a pro-osteogenic agent to enhance osteogenic differentiation of mesenchymal stem cells from human bone marrow: an in vitro study.

PubMed

Jin, Pan; Wu, Huayu; Xu, Guojie; Zheng, Li; Zhao, Jinmin

2014-05-01

The proliferation and osteogenic capacity of mesenchymal stem cells (MSCs) needs to be improved for their use in cell-based therapy for osteoporosis. (-)-Epigallocatechin-3-gallate (EGCG), one of the green tea catechins, has been widely investigated in studies of osteoblasts and osteoclasts. However, no consensus on its role as an osteogenic inducer has been reached, possibly because of the various types of cell lines examined and the range of concentrations of EGCG used. In this study, the osteogenic effects of EGCG are studied in primary human bone-marrow-derived MSCs (hBMSCs) by detecting cell proliferation, alkaline phosphatase (ALP) activity and the expression of relevant osteogenic markers. Our results show that EGCG has a strong stimulatory effect on hBMSCs developing towards the osteogenic lineage, especially at a concentration of 5 μM, as evidenced by an increased ALP activity, the up-regulated expression of osteogenic genes and the formation of bone-like nodules. Further exploration has indicated that EGCG directes osteogenic differentiation via the continuous up-regulation of Runx2. The underlying mechanism might involve EGCG affects on osteogenic differentiation through the modulation of bone morphogenetic protein-2 expression. EGCG has also been found to promote the proliferation of hBMSCs in a dose-dependent manner. This might be associated with its antioxidative effect leading to favorable amounts of reactive oxygen species in the cellular environment. Our study thus indicates that EGCG can be used as a pro-osteogenic agent for the stem-cell-based therapy of osteoporosis.

Quinopeptide formation associated with the disruptive effect of epigallocatechin-gallate on lysozyme fibrils.

PubMed

Cao, Na; Zhang, Yu-Jie; Feng, Shuang; Zeng, Cheng-Ming

2015-01-01

Numerous studies demonstrate that natural polyphenols can inhibit amyloid formation and disrupt preformed amyloid fibrils. In the present study, the fibril-disruptive effects of epigallocatechin-3-gallate (EGCG) were examined using lysozyme as a model protein. The results indicated that EGCG dose dependently inhibited lysozyme fibrillation and modified the peptide chains with quinonoid moieties under acidic conditions, as measured by ThT fluorescence, transmission electron microscopy, and an NBT-staining assay. Moreover, EGCG transformed the preformed lysozyme fibrils to amorphous aggregates through quinopeptide formation. The thiol blocker, N-ethylmaleimide, inhibited the disruptive effect of EGCG on preformed fibrils, suggesting that thiol groups are the binding sites for EGCG. We propose that the formation of quinone intermediates via oxidation and subsequent binding to lysozyme chains are the main processes driving the inhibition of amyloid formation and disruption of preformed fibrils by EGCG. The information presented in this study may provide fresh insight into the link between the antioxidant capacity and anti-amyloid activity of polyphenols. Copyright © 2015 Elsevier B.V. All rights reserved.

Spectrophotometric studies on the interaction between (-)-epigallocatechin gallate and lysozyme

NASA Astrophysics Data System (ADS)

Ghosh, Kalyan Sundar; Sahoo, Bijaya Ketan; Dasgupta, Swagata

2008-02-01

Various reported antibacterial activities of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea prompted us to study its binding with lysozyme. This has been investigated by fluorescence, circular dichroism (CD) and protein-ligand docking. The binding parameters were determined using a modified Stern-Volmer equation. The thermodynamic parameters are indicative of an initial hydrophobic association. The complex is, however, held together predominantly by van der Waals interactions and hydrogen bonding. CD studies do not indicate any significant changes in the secondary structure of lysozyme. Docking studies revealed that specific interactions are observed with residues Trp 62 and Trp 63.

The effects of gold nanoparticles in wound healing with antioxidant epigallocatechin gallate and α-lipoic acid.

PubMed

Leu, Jyh-Gang; Chen, Siang-An; Chen, Han-Min; Wu, Wen-Mein; Hung, Chi-Feng; Yao, Yeong-Der; Tu, Chi-Shun; Liang, Yao-Jen

2012-07-01

Topical applications of antioxidant agents in cutaneous wounds have attracted much attention. Gold nanoparticles (AuNPs), epigallocatechin gallate (EGCG), and α-lipoic acid (ALA) were shown to have antioxidative effects and could be helpful in wound healing. Their effects in Hs68 and HaCaT cell proliferation and in mouse cutaneous wound healing were studied. Both the mixture of EGCG + ALA (EA) and AuNPs + EGCG + ALA (AuEA) significantly increased Hs68 and HaCaT proliferation and migration. Topical AuEA application accelerated wound healing on mouse skin. Immunoblotting of wound tissue showed significant increase of vascular endothelial cell growth factor and angiopoietin-1 protein expression, but no change of angiopoietin-2 or CD31 after 7 days. After AuEA treatment, CD68 protein expression decreased and Cu/Zn superoxide dismutase increased significantly in the wound area. In conclusion, AuEA significantly accelerated mouse cutaneous wound healing through anti-inflammatory and antioxidation effects. This study may support future studies using other antioxidant agents in the treatment of cutaneous wounds. In this study, topically applied gold nanoparticles with epigallocatechin gallate and alpha-lipoic acid were studied regarding their effects in wound healing in cell cultures. Significant acceleration was demonstrated in wound healing in a murine model. Copyright © 2012 Elsevier Inc. All rights reserved.

In Vitro and In Silico Studies of the Molecular Interactions of Epigallocatechin-3-O-gallate (EGCG) with Proteins That Explain the Health Benefits of Green Tea.

PubMed

Saeki, Koichi; Hayakawa, Sumio; Nakano, Shogo; Ito, Sohei; Oishi, Yumiko; Suzuki, Yasuo; Isemura, Mamoru

2018-05-28

Green tea has been shown to have beneficial effects on many diseases such as cancer, obesity, inflammatory diseases, and neurodegenerative disorders. The major green tea component, epigallocatechin-3- O -gallate (EGCG), has been demonstrated to contribute to these effects through its anti-oxidative and pro-oxidative properties. Furthermore, several lines of evidence have indicated that the binding affinity of EGCG to specific proteins may explain its mechanism of action. This review article aims to reveal how EGCG-protein interactions can explain the mechanism by which green tea/EGCG can exhibit health beneficial effects. We conducted a literature search, using mainly the PubMed database. The results showed that several methods such as dot assays, affinity gel chromatography, surface plasmon resonance, computational docking analyses, and X-ray crystallography have been used for this purpose. These studies have provided evidence to show how EGCG can fit or occupy the position in or near functional sites and induce a conformational change, including a quaternary conformational change in some cases. Active site blocking, steric hindrance by binding of EGCG near an active site or induced conformational change appeared to cause inhibition of enzymatic activity and other biological activities of proteins, which are related to EGCG's biological oligomer and formation of their toxic aggregates, leading to the prevention of neurodegenerative diseases and amyloidosis. In conclusion, these studies have provided useful information on the action of green tea/catechins and would lead to future studies that will provide further evidence for rational EGCG therapy and use EGCG as a lead compound for drug design.

Epigallocatechin-3-gallate ameliorates insulin resistance in hepatocytes.

PubMed

Ma, Shan-Bo; Zhang, Rui; Miao, Shan; Gao, Bin; Lu, Yang; Hui, Sen; Li, Long; Shi, Xiao-Peng; Wen, Ai-Dong

2017-06-01

Hyperglycemia is a typical pathogenic factor in a series of complications among patients with type II diabetes. Epigallocatechin-3-gallate (EGCG) is the major polyphenol extracted from green tea and is reported to be an antioxidant. The aim of the present study was to examine the effect of EGCG on insulin resistance in human HepG2 cells pretreated with high concentrations of glucose. The protein kinase B (AKT)/glycogen synthase kinase (GSK) pathways were analyzed using western blot analysis in HepG2 cells and primary mouse hepatocytes treated with high glucose and/or EGCG. Cellular glycogen content was determined using a glycogen assay kit. Reactive oxygen species (ROS) production was determined using dihydroethidium staining and flow cytometry. c‑JUN N‑terminal kinase (JNK)/insulin receptor substrate 1 (IRS1)/AKT/GSK signaling was explored using western blot analysis in HepG2 cells treated with high glucose and/or EGCG or N-acetyl-cysteine. High glucose significantly decreased the levels of phosphorylated AKT and GSK in HepG2 cells and mouse primary hepatocytes. Pretreatment with EGCG significantly restored the activation of AKT and GSK in HepG2 cells and primary hepatocytes exposed to high glucose. In HepG2 cells and primary hepatocytes, glycogen synthesis was improved by EGCG treatment in a dose‑dependent manner. High glucose significantly stimulated the production of ROS while EGCG protected high glucose‑induced ROS production. ROS is known to serve a major role in high glucose induced‑insulin resistance by increasing JNK and IRS1 serine phosphorylation. In the present study, EGCG was observed to enhance the insulin‑signaling pathway. EGCG ameliorated high glucose‑induced insulin resistance in the hepatocytes by potentially decreasing ROS‑induced JNK/IRS1/AKT/GSK signaling.

Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced Toll-like receptor 4 (TLR4) activity via 67 kDa laminin receptor (67LR) in 3T3-L1 adipocytes.

PubMed

Bao, Suqing; Cao, Yanli; Zhou, Haicheng; Sun, Xin; Shan, Zhongyan; Teng, Weiping

2015-03-18

Obesity-related insulin resistance is associated with chronic systemic low-grade inflammation, and toll-like receptor 4 (TLR4) regulates inflammation. We investigated the pathways involved in epigallocatechin gallate (EGCG) modulation of insulin and TLR4 signaling in adipocytes. Inflammation was induced in adipocytes by lipopolysaccharide (LPS). An antibody against the 67 kDa laminin receptor (67LR, to which EGCG exclusively binds) was used to examine the effect of EGCG on TLR4 signaling, and a TLR4/MD-2 antibody was used to inhibit TLR4 activity and to determine the insulin sensitivity of differentiated 3T3-L1 adipocytes. We found that EGCG dose-dependently inhibited LPS stimulation of adipocyte inflammation by reducing inflammatory mediator and cytokine levels (IKKβ, p-NF-κB, TNF-α, and IL-6). Pretreatment with the 67LR antibody prevented EGCG inhibition of inflammatory cytokines, decreased glucose transporter isoform 4 (GLUT4) expression, and inhibited insulin-stimulated glucose uptake. TLR4 inhibition attenuated inflammatory cytokine levels and increased glucose uptake by reversing GLUT4 levels. These data suggest that EGCG suppresses TLR4 signaling in LPS-stimulated adipocytes via 67LR and attenuates insulin-stimulated glucose uptake associated with decreased GLUT4 expression.

Binding of (-)-epigallocatechin-3-gallate with thermally-induced bovine serum albumin/ι-carrageenan particles.

PubMed

Li, Jinbing; Wang, Xiaoyong

2015-02-01

Novel thermally-induced BSA/ι-carrageenan particles are used as a protective carrier for (-)-epigallocatechin-3-gallate (EGCG). The addition of EGCG to BSA/ι-carrageenan particles can highly quench the intrinsic fluorescence of BSA, which is explained in terms of the binding of EGCG to the hydrophobic pockets of BSA mainly through the hydrophobic force. According to the double logarithm equation, the binding constant is determined as 1.1×10(8)M(-1) for the binding of EGCG with BSA/ι-carrageenan particles. The high binding affinity is ascribed to both the molecular structure of EGCG and the partial unfolding state of BSA in BSA/ι-carrageenan particles. The circular dichroism spectra and calculated α-helix of BSA suggest that the bound EGCG leads to a more random secondary structure of BSA. Furthermore, BSA/ι-carrageenan particles are found to be superior to native BSA and pure BSA particles for improving the stability and radical scavenging activity of EGCG. Copyright © 2014 Elsevier Ltd. All rights reserved.

(-)Epigallocatechin-3-gallate decreases the stress-induced impairment of learning and memory in rats.

PubMed

Soung, Hung-Sheng; Wang, Mao-Hsien; Tseng, Hsiang-Chien; Fang, Hsu-Wei; Chang, Kuo-Chi

2015-08-18

Stress induces reactive oxygen species (ROS) and causes alterations in brain cytoarchitecture and cognition. Green tea has potent antioxidative properties especially the tea catechin (-) epigallocatechin-3-gallate (EGCG). These powerful antioxidative properties are able to protect against various oxidative damages. In this study we investigated the impact of stress on rats' locomotor activity, learning and memory. Many tea catechins, including EGCG, were examined for their possible therapeutic effects in treating stress-induced impairment. Our results indicated that locomotor activity was decreased, and the learning and memory were impaired in stressed rats (SRs). EGCG treatment was able to prevent the decreased locomotor activity as well as improve the learning and memory in SRs. EGCG treatment was also able to reduce the increased oxidative status in SRs' hippocampi. The above results suggest a therapeutic effect of EGCG in treating stress-induced impairment of learning and memory, most likely by means of its powerful antioxidative properties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Physiological effects of epigallocatechin-3-gallate (EGCG) on energy expenditure for prospective fat oxidation in humans: A systematic review and meta-analysis.

PubMed

Kapoor, Mahendra P; Sugita, Masaaki; Fukuzawa, Yoshitaka; Okubo, Tsutomu

2017-05-01

Green tea catechins (GTCs) are known to improve fat oxidation (FOX) during fasted, rested and exercise conditions wherein epigallocatechin-3-gallate (EGCG) is thought to be the most pharmacologically active and has been studied extensively. From the available data of randomized controlled trials (RCTs) on EGCG, we carried out a systematic review and meta-analysis to elucidate whether EGCG consumption indeed increase energy expenditure (EE) and promote FOX. A systematic review of the literature was conducted using electronic databases (PubMed, Embase, Cochrane Library, CINAHL, JICST, JSTPLUS, and JMEDPLUS and others) and eight RCTs were included. RCTs were reviewed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and methodological quality was assessed. After data extraction, results were aggregated using fixed- and random-effect approaches and expressed to quantify the relationship between the dose of EGCG for respiratory quotient (RQ), EE and rate of FOX to compare the EGCG and placebo treatments. The meta-analysis results of verities of studies in terms of dose and length of duration revealed that EGCG supplementation provided significant mean difference (MD) when compared with placebo for RQ [MD: -0.02; 95% confidence intervals (95% CI), -0.04 to 0.00; I 2 =67%; P=.01] and EE [MD: 158.05 kJ/day; 95% CI, 4.72 to 311.38; I 2 =0%; P=.04] in fixed-effect approach. Changes in FOX did not reach the level of statistical significance. Meta-analyses of EGCG influence on the body mass index, waist circumference and total body fat mass (TBFM) were also examined and their impact on the promotion of FOX is reported. Effect of EGCG doses was also systematically reviewed. Finding showed that EGCG intake moderately accelerates EE and reduces RQ. The analyses revealed that the EGCG resulted in difference in RQ and EE but the effect on the other measures of energy metabolism was relatively mild. Possibly, EGCG alone has the potential to increase

Antiglycation activity of lipophilized epigallocatechin gallate (EGCG) derivatives.

PubMed

Wang, Mingfu; Zhang, Xinchen; Zhong, Ying Joy; Perera, Nishani; Shahidi, Fereidoon

2016-01-01

Lipophilized EGCG derivatives were synthesized by esterification of EGCG with aliphatic fatty acids and demonstrated to possess many advantages, such as higher lipophilicity and apparent health benefits over the parent EGCG. This study used a total of seven lipophilized EGCG derivatives with fatty acids of different chain lengths attached and examined the impact of lipophilization on EGCG's antiglycation activity in vitro. The length of fatty acid chain was found to be an important factor, which positively correlated with ABTS radical scavenging capacity but long chain bulky substitutes prevented methylglyoxal (MGO) trapping. Except docosahexaenoic acid (DHA), lipophilization generally showed no interference with EGCG's in vitro inhibitory activity of advanced glycation endproducts (AGEs) formation. Therefore, the lipophilized EGCG derivatives are promising candidates worthy of further exploration for preventing AGEs accumulation in vivo and hence treating AGEs-associated diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synergistic effect of curcumin on epigallocatechin gallate-induced anticancer action in PC3 prostate cancer cells.

PubMed

Eom, Dae-Woon; Lee, Ji Hwan; Kim, Young-Joo; Hwang, Gwi Seo; Kim, Su-Nam; Kwak, Jin Ho; Cheon, Gab Jin; Kim, Ki Hyun; Jang, Hyuk-Jai; Ham, Jungyeob; Kang, Ki Sung; Yamabe, Noriko

2015-08-01

Epigallocatechin gallate (EGCG) and curcumin are well known to naturally-occurring anticancer agents. The aim of this study was to verify the combined beneficial anticancer effects of curcumin and EGCG on PC3 prostate cancer cells, which are resistant to chemotherapy drugs and apoptosis inducers. EGCG showed weaker inhibitory effect on PC3 cell proliferation than two other prostate cancer cell lines, LNCaP and DU145. Co-treatment of curcumin improved antiproliferative effect of EGCG on PC3 cells. The protein expressions of p21 were significantly increased by the co-treatment of EGCG and curcumin, whereas it was not changed by the treatment with each individual compound. Moreover, treatments of EGCG and curcumin arrested both S and G2/M phases of PC3 cells. These results suggest that the enhanced inhibitory effect of EGCG on PC3 cell proliferation by curcumin was mediated by the synergic up-regulation of p21-induced growth arrest and followed cell growth arrest.

Potentiation of Catechin Gallate-Mediated Sensitization of Staphylococcus aureus to Oxacillin by Nongalloylated Catechins†

PubMed Central

Stapleton, Paul D.; Shah, Saroj; Hara, Yukihiko; Taylor, Peter W.

2006-01-01

(−)−Epicatechin gallate (ECg) and (−)−epigallocatechin gallate (EGCg) reduce oxacillin resistance in mecA-containing strains of Staphylococcus aureus. Their binding to staphylococcal cells is enhanced by the nongalloyl analogues (−)−epicatechin (EC) and (−)−epigallocatechin (EGC). EC and EGC significantly increased the capacity of ECg and EGCg to reduce levels of staphylococcal oxacillin resistance. PMID:16436737

Novel epigallocatechin-3-gallate (EGCG) derivative as a new therapeutic strategy for reducing neuropathic pain after chronic constriction nerve injury in mice.

PubMed

Xifró, Xavier; Vidal-Sancho, Laura; Boadas-Vaello, Pere; Turrado, Carlos; Alberch, Jordi; Puig, Teresa; Verdú, Enrique

2015-01-01

Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG) polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI). First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi). We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p.) during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN), a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain.

Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with β-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

PubMed

Lee, Spencer; Razqan, Ghaida Saleh Al; Kwon, Dong H

2017-01-15

Infections caused by Acinetobacter baumannii were responsive to conventional antibiotic therapy. However, recently, carbapenem-associated multidrug resistant isolates have been reported worldwide and present a major therapeutic challenge. Epigallocatechin-3-Gallate (EGCG) extracted from green tea exhibits antibacterial activity. We evaluated the antibacterial activity of EGCG and possible synergism with antibiotics in carbapenem-associated multidrug resistant A. baumannii. A potential mechanism for synergism was also explored. Seventy clinical isolates of A. baumannii collected from geographically different areas were analyzed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EGCG. Checkerboard and time-killing assays were performed to exam the synergism between EGCG and antibiotics. The effects of EGCG on a multidrug efflux pump inhibitor (1-[1-naphthylmethyl] piperazine; NMP) and β-lactamase production were also examined in A. baumannii. Sixty-three of 70 clinical isolates of A. baumannii carried carbapenemase-encoding genes with carbapenem-associated multidrug resistance. Levels of MIC and MBC of EGCG ranged from 64 to 512µg/ml and from 128 to ≥1024µg/ml, respectively among the clinical isolates. MIC 90 and MBC 86 levels were 256µg/ml and 512µg/ml of EGCG, respectively. Subinhibitory concentration of EGCG in combination with all antibiotics tested, including carbapenem, sensitized (MICs fall≤1.0µg/ml) all carbapenem-associated multidrug resistant isolates. Checkerboard and time-killing assays showed synergism between EGCG and meropenem (or carbenicillin) counted as fractional inhibitory concentration of < 0.5 and cell numbers' decrease per ml of >2log10 within 12h, respectively. EGCG significantly increased the effect of NMP but was unrelated to β-lactamase production in A. baumannii, suggesting EGCG may be associated with inhibition of efflux pumps. Overall we suggest that EGCG-antibiotic combinations might

Long-Term Effects of (–)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats

PubMed Central

Leichsenring, Anna; Bäcker, Ingo; Furtmüller, Paul G.; Obinger, Christian; Lange, Franziska; Flemmig, Jörg

2016-01-01

Rheumatoid arthritis (RA)—a widespread chronic inflammatory disease in industrialized countries—is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the

Anti-proliferative and differentiation-inducing activities of the green tea catechin epigallocatechin-3-gallate (EGCG) on the human eosinophilic leukemia EoL-1 cell line.

PubMed

Lung, H L; Ip, W K; Wong, C K; Mak, N K; Chen, Z Y; Leung, K N

2002-12-06

A novel approach for the treatment of leukemia is the differentiation therapy in which immature leukemia cells are induced to attain a mature phenotype when exposed to differentiation inducers, either alone or in combinations with other chemotherapeutic or chemopreventive drugs. Over the past decade, numerous studies indicated that green tea catechins (GTC) could suppress the growth and induce apoptosis on a number of human cancer cell lines. However, the differentiation-inducing activity of GTC on human tumors remains poorly understood. In the present study, the effect of the major GTC epigallocatechin-3-gallate (EGCG) on the proliferation and differentiation of a human eosinophilc leukemic cell line, EoL-1, was examined. Our results showed that EGCG suppressed the proliferation of the EoL-1 cells in a dose-dependent manner, with an estimated IC(50) value of 31.5 microM. On the other hand, EGCG at a concentration of 40 microM could trigger the EoL-1 cells to undergo morphological differentiation into mature eosinophil-like cells. Using RT-PCR and flow cytometry, it was found that EGCG upregulated the gene and protein expression of two eosinophil-specific granule proteins, the major basic protein (MBP) and eosinophil peroxidase (EPO), in EoL-1 cells. Taken together, our findings suggest that EGCG can exhibit anti-leukemic activity on a human eosinophilic cell line EoL-1 by suppressing the proliferation and by inducing the differentiation of the leukemia cells.

Protection of epigallocatechin gallate against degradation during in vitro digestion using apple pomace as a carrier.

PubMed

Wu, Liangyu; Sanguansri, Luz; Augustin, Mary Ann

2014-12-17

Apple pomace, a byproduct of the apple juice processing industry, may be used as a matrix for carrying phytochemicals. High-pressure processing (600 MPa for 5 min) or heat treatment (121 °C for 5 min) of wet apple pomace can increase the shelf life of the pomace but may influence the carrier properties of the wet pomace for phytochemicals. We examined the effects of these processing treatments on the adsorption capacity of apple pomace for epigallocatechin gallate (EGCG) and the stability of EGCG in simulated gastrointestinal fluids in vitro. Both processing treatments reduced the adsorption capacity but protected EGCG against degradation in the simulated gastrointestinal fluids. The extent of EGCG degradation in simulated gastrointestinal fluids in vitro in the presence of apple pomace was not influenced by gastric and intestinal enzymes, suggesting that pH had the overriding influence on EGCG degradation. This study showed the potential of apple pomace as a carrier for EGCG in functional food applications.

Phase 2 trial of daily, oral epigallocatechin gallate in patients with light-chain amyloidosis.

PubMed

Meshitsuka, Sohsuke; Shingaki, Sumito; Hotta, Masatoshi; Goto, Miku; Kobayashi, Makoto; Ukawa, Yuuichi; Sagesaka, Yuko M; Wada, Yasuyo; Nojima, Masanori; Suzuki, Kenshi

2017-03-01

Previous studies have suggested that an increase in mitochondrial reactive oxygen species may cause organ damage in patients with light-chain (AL) amyloidosis; however, this damage can be decreased by antioxidant-agent treatment. Epigallocatechin gallate (EGCG), the major natural catechin in green tea, has potent antioxidant activity. Because EGCG has recently been reported to have a favorable toxicity profile for treating amyloidosis, we sought to examine the clinical efficacy and toxicity of EGCG in patients with AL amyloidosis. Fifty-seven patients were randomly assigned to the EGCG and observation groups and observed for six months. There were no increases in grade 3-5 adverse events and EGCG therapy was well tolerated. Although a decrease in the urinary albumin level was found in the EGCG group in patients with obvious albuminuria after treatment initiation, its antioxidant activity may not be sufficient to clarify the potential effect of EGCG in patients with AL amyloidosis. Because some of the biological markers responsible for organ damage were well correlated to the level of antioxidant potential in patients' plasma, the status of oxidative stress in the blood may indicate the extent of organ damage in clinical situations.

(-)Epigallocatechin-3-gallate prevents the reserpine-induced impairment of short-term social memory in rats.

PubMed

Tseng, Hsiang-Chien; Wang, Mao-Hsien; Soung, Hung-Sheng; Chang, Yi; Chang, Kuo-Chi

2015-12-01

Reserpine has been confirmed to induce cognitive dysfunction and increase brain neural oxidative stress. Green tea catechins, particularly (-)epigallocatechin-3-gallate (EGCG), have strong antioxidative properties and can protect against numerous oxidative damages. In this study, we examined the possible protective effects of EGCG on reserpine-induced impairment of short-term memory in rats. Reserpine (1 mg/kg, intraperitoneal)-induced memory impairment was assessed using the social recognition task method; locomotor activity and the olfactory discrimination ability were not altered as measured by an open-field test and an olfactory discrimination test, respectively. EGCG treatment (100 and 300 mg/kg, intraperitoneal, for 7 days, starting 6 days before the reserpine injection) could improve the worsened social memory of reserpine-treated rats. Also, EGCG treatment reduced reserpine-induced lipid peroxidation and enhanced the antioxidation power in the hippocampi of reserpine-treated rats. These results suggest a protective effect of EGCG in treating reserpine-induced impairment of memory, most probably through its powerful antioxidative activities. Accordingly, EGCG may hold a clinically relevant value in preventing reserpine-induced cognitive dysfunction.

Inhibition of starch digestion by the green tea polyphenol, (−)-epigallocatechin-3-gallate

PubMed Central

Forester, Sarah C.; Gu, Yeyi; Lambert, Joshua D.

2013-01-01

Scope Green tea has been shown to ameliorate symptoms of metabolic syndrome in vivo. The effects could be due, in part, to modulation of postprandial blood glucose levels. Methods and results We examined the effect of coadministration of (−)-epigallocatechin-3-gallate (EGCG, 100 mg/kg, i.g.) on blood glucose levels following oral administration of common corn starch (CCS), maltose, sucrose, or glucose to fasted CF-1 mice. We found that cotreatment with EGCG significantly reduced postprandial blood glucose levels after administration of CCS compared to control mice (50 and 20% reduction in peak blood glucose levels and blood glucose area under the curve, respectively). EGCG had no effect on postprandial blood glucose following administration of maltose or glucose, suggesting that EGCG may modulate amylase-mediated starch digestion. In vitro, EGCG noncompetitively inhibited pancreatic amylase activity by 34% at 20 μM. No significant change was induced in the expression of two small intestinal glucose transporters (GLUT2 and SGLT1). Conclusions Our results suggest that EGCG acutely reduces postprandial blood glucose levels in mice when coadministered with CCS and this may be due in part to inhibition of α-amylase. The relatively low effective dose of EGCG makes a compelling case for studies in human subjects. PMID:23038646

Covalent modification of soy protein isolate by (-)-epigallocatechin-3-gallate: effects on structural and emulsifying properties.

PubMed

Tao, Fei; Jiang, He; Chen, Wenwei; Zhang, Yongyong; Pan, Jiarong; Jiang, Jiaxin; Jia, Zhenbao

2018-05-07

Soy protein isolate (SPI) has promising applications in various food products because of its excellent functional properties and nutritional quality. The structural and emulsifying properties of covalently modified SPI by (-)-epigallocatechin-3-gallate (EGCG) were investigated. SPI was covalently modified by EGCG under alkaline conditions. SDS-PAGE analysis revealed that EGCG modification caused cross-linking of SPI proteins. Circular dichroism spectra demonstrated that the secondary structure of SPI proteins was changed by EGCG modification. In addition, the modifications resulted in the perturbation of the tertiary structure of SPI as evidenced by intrinsic fluorescence spectra and surface hydrophobicity measurements. Oil-in-water emulsions of modified SPI had smaller droplet sizes and better creaming stability compared to those from unmodified SPI. The covalent modification by EGCG improved the emulsifying property of SPI. This study provided an innovative approach for improving the emulsifying properties of proteins. This article is protected by copyright. All rights reserved.

The green tea polyphenol (-)-epigallocatechin gallate precipitates salivary proteins including alpha-amylase: biochemical implications for oral health.

PubMed

Hara, Kumiko; Ohara, Masaru; Hayashi, Ikue; Hino, Takamune; Nishimura, Rumi; Iwasaki, Yoriko; Ogawa, Tetsuji; Ohyama, Yoshihiko; Sugiyama, Masaru; Amano, Hideaki

2012-04-01

Green tea is a popular drink throughout the world, and it contains various components, including the green tea polyphenol (-)-epigallocatechin gallate (EGCG). Tea interacts with saliva upon entering the mouth, so the interaction between saliva and EGCG interested us, especially with respect to EGCG-protein binding. SDS-PAGE revealed that several salivary proteins were precipitated after adding EGCG to saliva. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) peptide mass fingerprinting indicated that the major proteins precipitated by EGCG were alpha-amylase, S100, and cystatins. Surface plasmon resonance revealed that EGCG bound to alpha-amylase at dissociation constant (K(d)) = 2.74 × 10(-6) M, suggesting that EGCG interacts with salivary proteins with a relatively strong affinity. In addition, EGCG inhibited the activity of alpha-amylase by non-competitive inhibition, indicating that EGCG is effective at inhibiting the formation of fermentable carbohydrates involved in caries formation. Interestingly, alpha-amylase reduced the antimicrobial activity of EGCG against the periodontal bacterium Aggregatibacter actinomycetemcomitans. Therefore, we considered that EGCG-salivary protein interactions might have both protective and detrimental effects with respect to oral health. © 2012 Eur J Oral Sci.

Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the expression of HIF-1α and P-gp in the human pancreatic carcinoma cell line PANC-1.

PubMed

Zhu, Zhenni; Wang, Yu; Liu, Zhiqing; Wang, Fan; Zhao, Qiu

2012-05-01

The aim of this study was to verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on cell proliferation and the expression of hypoxia-inducible factor 1 (HIF-1α) and multidrug resistance protein 1 (MDR1/P-gp) in the human pancreatic carcinoma cell line PANC-1, thereby, reversing drug resistance of pancreatic carcinoma and improving its sensitivity to cancer chemotherapy. The human pancreatic carcinoma cell line PANC-1 was incubated under hypoxic conditions with different concentrations of epigallocatechin-3-gallate (EGCG) for indicated hours. The effects of EGCG on the mRNA or protein expression of HIF-1α and MDR1 were determined by RT-PCR or western blotting. Cellular proliferation and viability assays were measured using Cell Counting Kit-8. Western blotting revealed that EGCG inhibits the expression of the HIF-1α protein in a dose-dependent manner, while RT-PCR showed that it does not have any effects on HIF-1α mRNA. In addition, EGCG attenuated the mRNA and protein levels of P-gp in a dose-dependent manner, reaching a peak at the highest concentration. Furthermore, EGCG inhibited the proliferation of PANC-1 cells in a concentration- and time-dependent manner. The attenuation of HIF-1α and the consequently reduced P-gp could contribute to the inhibitory effects of EGCG on the proliferation of PANC-1 cells.

(−)-Epigallocatechin Gallate Targets Notch to Attenuate the Inflammatory Response in the Immediate Early Stage in Human Macrophages

PubMed Central

Wang, Tengfei; Xiang, Zemin; Wang, Ya; Li, Xi; Fang, Chongye; Song, Shuang; Li, Chunlei; Yu, Haishuang; Wang, Han; Yan, Liang; Hao, Shumei; Wang, Xuanjun; Sheng, Jun

2017-01-01

Inflammation plays important roles at different stages of diabetes mellitus, tumorigenesis, and cardiovascular diseases. (−)-Epigallocatechin gallate (EGCG) can attenuate inflammatory responses effectively. However, the immediate early mechanism of EGCG in inflammation remains unclear. Here, we showed that EGCG attenuated the inflammatory response in the immediate early stage of EGCG treatment by shutting off Notch signaling and that the effect did not involve the 67-kDa laminin receptor, the common receptor for EGCG. EGCG eliminated mature Notch from the cell membrane and the nuclear Notch intercellular domain, the active form of Notch, within 2 min by rapid degradation via the proteasome pathway. Transcription of the Notch target gene was downregulated simultaneously. Knockdown of Notch 1/2 expression by RNA interference impaired the downregulation of the inflammatory response elicited by EGCG. Further study showed that EGCG inhibited lipopolysaccharide-induced inflammation and turned off Notch signaling in human primary macrophages. Taken together, our results show that EGCG targets Notch to regulate the inflammatory response in the immediate early stage. PMID:28443100

Improving anticancer efficacy of (–)-epigallocatechin-3-gallate gold nanoparticles in murine B16F10 melanoma cells

PubMed Central

Chen, Cheng-Cheung; Hsieh, Dar-Shih; Huang, Kao-Jean; Chan, Yi-Lin; Hong, Po-Da; Yeh, Ming-Kung; Wu, Chang-Jer

2014-01-01

(–)-Epigallocatechin-3-gallate (EGCG), the major bioactive constituent in green tea, has been reported to effectively inhibit the formation and development of tumors. To maximize the effectiveness of EGCG, we attached it to nanogold particles (EGCG-pNG) in various ratios to examine in vitro cytotoxicity and in vivo anti-cancer activity. EGCG-pNG showed improved anti-cancer efficacy in B16F10 murine melanoma cells; the cytotoxic effect in the melanoma cells treated with EGCG-pNG was 4.91 times higher than those treated with EGCG. The enhancement is achieved through mitochondrial pathway-mediated apoptosis as determined by annexin V assay, JC-10 staining, and caspase-3, -8, -9 activity assay. Moreover, EGCG-pNG was 1.66 times more potent than EGCG for inhibition of tumor growth in a murine melanoma model. In the hemolysis assay, the pNG surface conjugated with EGCG is most likely the key factor that contributes to the decreased release of hemoglobin from human red blood cells. PMID:24855338

Epigallocatechin Gallate: A Review of Its Beneficial Properties to Prevent Metabolic Syndrome

PubMed Central

Legeay, Samuel; Rodier, Marion; Fillon, Laetitia; Faure, Sébastien; Clere, Nicolas

2015-01-01

Obesity and being overweight are linked with a cluster of metabolic and vascular disorders that have been termed the metabolic syndrome. This syndrome promotes the incidence of cardiovascular diseases that are an important public health problem because they represent a major cause of death worldwide. Whereas there is not a universally-accepted set of diagnostic criteria, most expert groups agree that this syndrome is defined by an endothelial dysfunction, an impaired insulin sensitivity and hyperglycemia, dyslipidemia, abdominal obesity and hypertension. Epidemiological studies suggest that the beneficial cardiovascular health effects of diets rich in green tea are, in part, mediated by their flavonoid content, with particular benefits provided by members of this family such as epigallocatechin gallate (EGCG). Although their bioavailability is discussed, various studies suggest that EGCG modulates cellular and molecular mechanisms of various symptoms leading to metabolic syndrome. Therefore, according to in vitro and in vivo model data, this review attempts to increase our understanding about the beneficial properties of EGCG to prevent metabolic syndrome. PMID:26198245

Interaction between Pin1 and its natural product inhibitor epigallocatechin-3-gallate by spectroscopy and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Xi, Lei; Wang, Yu; He, Qing; Zhang, Qingyan; Du, Linfang

2016-12-01

The binding of epigallocatechin-3-gallate (EGCG) to wild type Pin1 in solution was studied by spectroscopic methods and molecular dynamics simulations in this research to explore the binding mode and inhibition mechanism. The binding constants and number of binding sites per Pin1 for EGCG were calculated through the Stern-Volmer equation. The values of binding free energy and thermodynamic parameters were calculated and indicated that hydrogen bonds, electrostatic interaction and Van der Waals interaction played the major role in the binding process. The alterations of Pin1 secondary structure in the presence of EGCG were confirmed by far-UV circular dichroism spectra. The binding model at atomic-level revealed that EGCG was bound to the Glu12, Lys13, Arg14, Met15 and Arg17 in WW domain. Furthermore, EGCG could also interact with Arg69, Asp112, Cys113 and Ser114 in PPIase domain.

Multi-site binding of epigallocatechin gallate to human serum albumin measured by NMR and isothermal titration calorimetry

PubMed Central

Eaton, Joshua D.

2017-01-01

The affinity of epigallocatechin gallate (EGCG) for human serum albumin (HSA) was measured in physiological conditions using NMR and isothermal titration calorimetry (ITC). NMR estimated the Ka (self-dissociation constant) of EGCG as 50 mM. NMR showed two binding events: strong (n1=1.8 ± 0.2; Kd1 =19 ± 12 μM) and weak (n2∼20; Kd2 =40 ± 20 mM). ITC also showed two binding events: strong (n1=2.5 ± 0.03; Kd1 =21.6 ± 4.0 μM) and weak (n2=9 ± 1; Kd2 =22 ± 4 mM). The two techniques are consistent, with an unexpectedly high number of bound EGCG. The strong binding is consistent with binding in the two Sudlow pockets. These results imply that almost all EGCG is transported in the blood bound to albumin and explains the wide tissue distribution and chemical stability of EGCG in vivo. PMID:28424370

Epigallocatechin gallate incorporation into lignin enhances the alkaline delignification and enzymatic saccharification of cell walls

PubMed Central

2012-01-01

Background Lignin is an integral component of the plant cell wall matrix but impedes the conversion of biomass into biofuels. The plasticity of lignin biosynthesis should permit the inclusion of new compatible phenolic monomers such as flavonoids into cell wall lignins that are consequently less recalcitrant to biomass processing. In the present study, epigallocatechin gallate (EGCG) was evaluated as a potential lignin bioengineering target for rendering biomass more amenable to processing for biofuel production. Results In vitro peroxidase-catalyzed polymerization experiments revealed that both gallate and pyrogallyl (B-ring) moieties in EGCG underwent radical cross-coupling with monolignols mainly by β–O–4-type cross-coupling, producing benzodioxane units following rearomatization reactions. Biomimetic lignification of maize cell walls with a 3:1 molar ratio of monolignols and EGCG permitted extensive alkaline delignification of cell walls (72 to 92%) that far exceeded that for lignified controls (44 to 62%). Alkali-insoluble residues from EGCG-lignified walls yielded up to 34% more glucose and total sugars following enzymatic saccharification than lignified controls. Conclusions It was found that EGCG readily copolymerized with monolignols to become integrally cross-coupled into cell wall lignins, where it greatly enhanced alkaline delignification and subsequent enzymatic saccharification. Improved delignification may be attributed to internal trapping of quinone-methide intermediates to prevent benzyl ether cross-linking of lignin to structural polysaccharides during lignification, and to the cleavage of ester intra-unit linkages within EGCG during pretreatment. Overall, our results suggest that apoplastic deposition of EGCG for incorporation into lignin would be a promising plant genetic engineering target for improving the delignification and saccharification of biomass crops. PMID:22889353

Probing the inhibitory potency of epigallocatechin gallate against human γB-crystallin aggregation: Spectroscopic, microscopic and simulation studies

NASA Astrophysics Data System (ADS)

Chaudhury, Susmitnarayan; Dutta, Anirudha; Bag, Sudipta; Biswas, Pranandita; Das, Amit Kumar; Dasgupta, Swagata

2018-03-01

Aggregation of human ocular lens proteins, the crystallins is believed to be one of the key reasons for age-onset cataract. Previous studies have shown that human γD-crystallin forms amyloid like fibres under conditions of low pH and elevated temperature. In this article, we have investigated the aggregation propensity of human γB-crystallin in absence and presence of epigallocatechin gallate (EGCG), in vitro, when exposed to stressful conditions. We have used different spectroscopic and microscopic techniques to elucidate the inhibitory effect of EGCG towards aggregation. The experimental results have been substantiated by molecular dynamics simulation studies. We have shown that EGCG possesses inhibitory potency against the aggregation of human γB-crystallin at low pH and elevated temperature.

Novel epigallocatechin gallate analogs as potential anticancer agents: a patent review (2009 – present)

PubMed Central

Landis-Piwowar, Kristin; Chen, Di; Foldes, Robert; Chan, Tak-Hang; Dou, Qing Ping

2013-01-01

Introduction Over the past three years numerous patents and patent applications have been published relating to scientific advances in the use of the green tea polyphenol epigallocatechin gallate (EGCG) (the most abundant, and bioactive compound in green tea) and its analogs as anticancer agents. EGCG affects multiple molecular targets involved in cancer cell proliferation and survival; however, polyphenolic catechins, such as EGCG, generally exhibit poor oral bioavailability. Since the anticancer activity of polyphenols largely depends on their susceptibility to biotransformation reactions, numerous EGCG derivatives, analogs and prodrugs have been designed to improve the stability, bioavailability and anticancer potency of the native compound. Areas covered This review focuses on the applications of EGCG and its analogs, derivatives and prodrugs in the prevention and treatment of human cancers. A comprehensive description of patents related to EGCG and its derivatives, analogs and prodrugs and their uses as anticancer agents is included. Expert opinion EGCG targets multiple essential survival proteins and pathways in human cancer cells. Because it is unstable physiologically, numerous alterations to the EGCG molecule have been patented, either to improve the integrity of the native compound or to generate a more stable yet similarly efficacious molecule. EGCG and its derivatives, analogs and prodrugs could be developed into future drugs for chemoprevention, chemosensitization, radiosensitization and/or cancer interception. PMID:23230990

Epigallocatechin Gallate-Modified Gelatin Sponges Treated by Vacuum Heating as a Novel Scaffold for Bone Tissue Engineering.

PubMed

Honda, Yoshitomo; Takeda, Yoshihiro; Li, Peiqi; Huang, Anqi; Sasayama, Satoshi; Hara, Eiki; Uemura, Naoya; Ueda, Mamoru; Hashimoto, Masanori; Arita, Kenji; Matsumoto, Naoyuki; Hashimoto, Yoshiya; Baba, Shunsuke; Tanaka, Tomonari

2018-04-11

Chemical modification of gelatin using epigallocatechin gallate (EGCG) promotes bone formation in vivo. However, further improvements are required to increase the mechanical strength and bone-forming ability of fabricated EGCG-modified gelatin sponges (EGCG-GS) for practical applications in regenerative therapy. In the present study, we investigated whether vacuum heating-induced dehydrothermal cross-linking of EGCG-GS enhances bone formation in critical-sized rat calvarial defects. The bone-forming ability of vacuum-heated EGCG-GS (vhEGCG-GS) and other sponges was evaluated by micro-computed tomography and histological staining. The degradation of sponges was assessed using protein assays, and cell morphology and proliferation were verified by scanning electron microscopy and immunostaining using osteoblastic UMR106 cells in vitro. Four weeks after the implantation of sponges, greater bone formation was detected for vhEGCG-GS than for EGCG-GS or vacuum-heated gelatin sponges (dehydrothermal cross-linked sponges without EGCG). In vitro experiments revealed that the relatively low degradability of vhEGCG-GS supports cell attachment, proliferation, and cell-cell communication on the matrix. These findings suggest that vacuum heating enhanced the bone forming ability of EGCG-GS, possibly via the dehydrothermal cross-linking of EGCG-GS, which provides a scaffold for cells, and by maintaining the pharmacological effect of EGCG.

Quercetin increased the antiproliferative activity of green tea polyphenol (−)-epigallocatechin gallate in prostate cancer cells

PubMed Central

Wang, Piwen; Heber, David; Henning, Susanne M.

2012-01-01

We previously demonstrated that 50% of (−)-epigallocatechin gallate (EGCG) was present in methylated form (4″-MeEGCG) in human prostate tissue, which is less bioactive. We therefore investigated whether quercetin, a natural inhibitor of catechol-O-methyl transferase (COMT), will inhibit EGCG methylation leading to enhanced antiproliferative activity of EGCG in prostate cancer cells. Incubation with both, quercetin and EGCG, for 2 hr increased the cellular concentrations of EGCG by 4 to 8-fold and 6 to 10-fold in androgen-independent PC-3 cells and androgen-dependent LNCaP cells, respectively. Concurrently, the percent of 4″-MeEGCG in the total EGCG was decreased from 39% to 15% in PC-3 cells and from 61% to 38% in LNCaP cells. Quercetin and EGCG in combination synergistically inhibited cell proliferation, caused cell cycle arrest and induced apoptosis in PC-3 cells. In LNCaP cells EGCG and quercetin exhibited a stronger antiproliferative activity leading to an additive effect. The synergistic effect of these two agents in PC-3 cells could be based on the fact that EGCG primarily inhibited COMT activity while quercetin reduced the amount of COMT protein. In summary, quercetin combined with EGCG in vitro demonstrated enhanced inhibition of cell proliferation by increasing the intracellular concentration of EGCG and decreasing EGCG methylation. PMID:22452782

Chemopreventive effect of epigallocatechin-3-gallate (EGCG) and folic acid on the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rat model.

PubMed

Xu, Qi; Yang, Chuan Hua; Liu, Qiang; Jin, Xi Feng; Xu, Xi Tao; Tong, Jin Lu; Xiao, Shu Dong; Ran, Zhi Hua

2011-06-01

To investigate the chemopreventive effect and mechanisms of epigallocatechin-3-gallate (EGCG) and folic acid on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rats, and to investigate and compare the combinatorial effects of EGCG and folic acid on the chemoprevention of gastrointestinal carcinogenesis. A total of 159 healthy male Wistar rats were randomly divided into seven groups to have the MNNG in drink (group M), MNNG in drink and EGCG in the feed (group ME), MNNG in drink and folic acid in the feed (group MF), MNNG in drink and EGCG+folic acid in the feed (group MEF), EGCG in the feed (group E), folic acid in the feed (group F) or normal feed (group C), respectively. At 44 weeks, all the rats were killed and assessed for the presence of gastrointestinal tumor. The occurrence of cancer was evaluated by histology. Ki-67 in cancerous tissues and in situ apoptosis were determined by immunohistochemical staining or terminal deoxyribonucleotide transferase-mediated nick-end labeling (TUNEL) assay, respectively. The experiment was completed in 157 rats (98.74%). As compared with group M, the tumor incidence of group MEF decreased significantly (P=0.011). Ki-67 expression in cancerous tissues of group ME and MEF also decreased significantly (P=0.038, P=0.009), while apoptosis of group ME, MF and MEF increased significantly (P=0.000, P=0.003, P=0.000). EGCG combined with folic acid has an obvious chemopreventive effect on gastrointestinal carcinogenesis induced by MNNG in rats. © 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Human cancer stem cells are a target for cancer prevention using (-)-epigallocatechin gallate.

PubMed

Fujiki, Hirota; Sueoka, Eisaburo; Rawangkan, Anchalee; Suganuma, Masami

2017-12-01

Our previous experiments show that the main constituent of green-tea catechins, (-)-epigallocatechin gallate (EGCG), completely prevents tumor promotion on mouse skin initiated with 7,12-dimethylbenz(a)anthracene followed by okadaic acid and that EGCG and green tea extract prevent cancer development in a wide range of target organs in rodents. Therefore, we focused our attention on human cancer stem cells (CSCs) as targets of cancer prevention and treatment with EGCG. The numerous reports concerning anticancer activity of EGCG against human CSCs enriched from cancer cell lines were gathered from a search of PubMed, and we hope our review of the literatures will provide a broad selection for the effects of EGCG on various human CSCs. Based on our theoretical study, we discuss the findings as follows: (1) Compared with the parental cells, human CSCs express increased levels of the stemness markers Nanog, Oct4, Sox2, CD44, CD133, as well as the EMT markers, Twist, Snail, vimentin, and also aldehyde dehydrogenase. They showed decreased levels of E-cadherin and cyclin D1. (2) EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs. (3) EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs. (4) The inhibition of EGCG of the stemness of CSCs was weaker compared with parental cells. (5) The weak inhibitory activity of EGCG increased synergistically in combination with anticancer drugs. Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.

Epigallocatechin-3-gallate (EGCG) activates AMPK through the inhibition of glutamate dehydrogenase in muscle and pancreatic ß-cells: A potential beneficial effect in the pre-diabetic state?

PubMed

Pournourmohammadi, Shirin; Grimaldi, Mariagrazia; Stridh, Malin H; Lavallard, Vanessa; Waagepetersen, Helle S; Wollheim, Claes B; Maechler, Pierre

2017-07-01

Glucose homeostasis is determined by insulin secretion from the ß-cells in pancreatic islets and by glucose uptake in skeletal muscle and other insulin target tissues. While glutamate dehydrogenase (GDH) senses mitochondrial energy supply and regulates insulin secretion, its role in the muscle has not been elucidated. Here we investigated the possible interplay between GDH and the cytosolic energy sensing enzyme 5'-AMP kinase (AMPK), in both isolated islets and myotubes from mice and humans. The green tea polyphenol epigallocatechin-3-gallate (EGCG) was used to inhibit GDH. Insulin secretion was reduced by EGCG upon glucose stimulation and blocked in response to glutamine combined with the allosteric GDH activator BCH (2-aminobicyclo-[2,2,1] heptane-2-carboxylic acid). Insulin secretion was similarly decreased in islets of mice with ß-cell-targeted deletion of GDH (ßGlud1 -/- ). EGCG did not further reduce insulin secretion in the mutant islets, validating its specificity. In human islets, EGCG attenuated both basal and nutrient-stimulated insulin secretion. Glutamine/BCH-induced lowering of AMPK phosphorylation did not operate in ßGlud1 -/- islets and was similarly prevented by EGCG in control islets, while high glucose systematically inactivated AMPK. In mouse C2C12 myotubes, like in islets, the inhibition of AMPK following GDH activation with glutamine/BCH was reversed by EGCG. Stimulation of GDH in primary human myotubes caused lowering of insulin-induced 2-deoxy-glucose uptake, partially counteracted by EGCG. Thus, mitochondrial energy provision through anaplerotic input via GDH influences the activity of the cytosolic energy sensor AMPK. EGCG may be useful in obesity by resensitizing insulin-resistant muscle while blunting hypersecretion of insulin in hypermetabolic states. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of the aggregation of lactoferrin and (-)-epigallocatechin gallate in the presence of polyphenols, oligosaccharides, and collagen peptide.

PubMed

Yang, Wei; Liu, Fuguo; Xu, Chenqi; Sun, Cuixia; Yuan, Fang; Gao, Yanxiang

2015-05-27

The aggregation of lactoferrin and (-)-epigallocatechin gallate (EGCG) was inhibited by polyphenols, oligosaccharides, and collagen peptide in this study. Polyphenols, oligosaccharides, or collagen peptide can effectively prevent the formation of lactoferrin-EGCG aggregates, respectively. The addition sequence of lactoferrin, polyphenols (oligosaccharides or collagen peptide) and EGCG can affect the turbidity and particle size of the ternary complexes in the buffer solution; however, it hardly affected the ζ-potential and fluorescence characteristics. With either positive or negative charge, polyphenols and collagen peptide disrupted the formation of lactoferrin-EGCG aggregate mainly through the mechanism of its competition with EGCG molecules which surrounded the lactoferrin molecule surface with weaker binding affinities, forming polyphenols or a collagen peptide-lactoferrin-EGCG ternary complex; for neutral oligosaccharides, the ternary complex was generated mainly through steric effects, accompanied by a change in the lactoferrin secondary structure induced by gallic acid, chlorogenic acid, and xylo-oligosaccharide. Polyphenols, oligosaccharides, or collagen peptide restraining the formation of lactoferrin-EGCG aggregate could be applied in the design of clear products in the food, pharmaceutical, and cosmetic industries.

Epigallocatechin-3-gallate(EGCG) : mechanisms and the combined applications.

PubMed

Song, Xuekun; Du, Juan; Zhao, Wenyuan; Guo, Zheng

2017-12-17

EGCG is the most important pharmacological component in tea. Researches have confirmed its effects, including anti-tumor, anti-inflammation, anti-aging, anti-obesity, anti-diabetic, cardiovascular disease prevention and protection, immunoregulation and neuroprotection. Paradoxically, the clinical application of EGCG is very rare. One of the most important reasons is its poor stability and low bioavailability. Excepting for altering the dosage form or synthesizing the analogues to overcome the loss during absorption, an increasing number of studies indicate that EGCG can exert certain auxiliary effect and enhance chemosensitivity in combined medication. The pharmacological action, the pharmacology network including mutation of signaling receptor and modulation of intracellular signaling pathway, and the combination treatment strategy of EGCG are clarified and sorted out, both the possible targets and combinatorial applications based on the characteristics of EGCG are systematically summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3

PubMed Central

Li, Sainan; Xia, Yujing; Chen, Kan; Li, Jingjing; Liu, Tong; Wang, Fan; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

2016-01-01

Background Epigallocatechin-3-gallate (EGCG) is the most effective compound in green tea, and possesses a wide range of beneficial effects, including anti-inflammatory, antioxidant, antiobesity, and anticancer effects. In this study, we investigated the protective effects of EGCG in concanavalin A (ConA)-induced hepatitis in mice and explored the possible mechanisms involved in these effects. Methods Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and EGCG (10 or 30 mg/kg) was administered orally twice daily for 10 days before ConA injection. Serum liver enzymes, proinflammatory cytokines, and other marker proteins were determined 2, 8, and 24 hours after the ConA administration. Results BNIP3 mediated cell apoptosis and autophagy in ConA-induced hepatitis. EGCG decreased the immunoreaction and pathological damage by reducing inflammatory factors, such as TNF-α, IL-6, IFN-γ, and IL-1β. EGCG also exhibited an antiapoptotic and antiautophagic effect by inhibiting BNIP3 via the IL-6/JAKs/STAT3 pathway. Conclusion EGCG attenuated liver injury in ConA-induced hepatitis by downregulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy. PMID:26929598

Validation of a high performance liquid chromatography method for the stabilization of epigallocatechin gallate.

PubMed

Fangueiro, Joana F; Parra, Alexander; Silva, Amélia M; Egea, Maria A; Souto, Eliana B; Garcia, Maria L; Calpena, Ana C

2014-11-20

Epigallocatechin gallate (EGCG) is a green tea catechin with potential health benefits, such as anti-oxidant, anti-carcinogenic and anti-inflammatory effects. In general, EGCG is highly susceptible to degradation, therefore presenting stability problems. The present paper was focused on the study of EGCG stability in HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) medium regarding the pH dependency, storage temperature and in the presence of ascorbic acid a reducing agent. The evaluation of EGCG in HEPES buffer has demonstrated that this molecule is not able of maintaining its physicochemical properties and potential beneficial effects, since it is partially or completely degraded, depending on the EGCG concentration. The storage temperature of EGCG most suitable to maintain its structure was shown to be the lower values (4 or -20 °C). The pH 3.5 was able to provide greater stability than pH 7.4. However, the presence of a reducing agent (i.e., ascorbic acid) was shown to provide greater protection against degradation of EGCG. A validation method based on RP-HPLC with UV-vis detection was carried out for two media: water and a biocompatible physiological medium composed of Transcutol®P, ethanol and ascorbic acid. The quantification of EGCG for purposes, using pure EGCG, requires a validated HPLC method which could be possible to apply in pharmacokinetic and pharmacodynamics studies. Copyright © 2014. Published by Elsevier B.V.

Photodegradation of (-)-epigallocatechin-3-gallate in topical cream formulations and its photostabilization.

PubMed

Bianchi, Anna; Marchetti, Nicola; Scalia, Santo

2011-12-05

The aim of the study was to examine the photostability of the major catechin of green tea, (-)-epigallocatechin-3-gallate (EGCG), which possesses important antioxidant and skin photoprotective properties. In order to simulate realistic conditions of use of topical preparations, the photolysis studies were performed in model creams (oil-in-water emulsions) containing 1% (w/w) EGCG and exposed to a solar simulator at an irradiance corresponding to natural sunlight. The extent of photodegradation was measured by HPLC-UV and HPLC-ESI-MS. EGCG was found to decompose by 68.9±2.3%, after 1h irradiation. Addition of the coantioxidants, vitamin E or butylated hydroxytoluene to the emulsion formulation, significantly enhanced the photolability of the catechin, the EGCG loss reached 85.7±1.3% and 80.5±1.4%, respectively. On the other hand, inclusion of the UVB (290-320nm) filter, ethylhexyl methoxycinnamate in the cream produced a small but significant reduction of EGCG photodegradation to 61.0±2.9%, while the UVA (320-400nm) filter, butyl methoxydibenzoylmethane was ineffective (EGCG degradation, 67.8±1.5%). A more marked decrease in the light-induced decomposition of EGCG to 51.6±2.7% was achieved, under the same conditions, using the water-soluble UVB filter, benzophenone-4 (BP-4). This effect was concentration dependent, maximal EGCG photostabilization (catechin loss, 29.4±2.2%) was attained in the presence of 2.1% (w/w) BP-4. Therefore, BP-4 represents a useful additive to improve the light stability of EGCG in topical formulations for skin photoprotection. Copyright © 2011 Elsevier B.V. All rights reserved.

Stability of Polyphenols Epigallocatechin Gallate and Pentagalloyl Glucose in a Simulated Digestive System

PubMed Central

Krook, Melanie A.; Hagerman, Ann E.

2012-01-01

Polyphenols found in foods and beverages are under intense scrutiny for their potential beneficial effects on human health. We examined the stability of two bioactive polyphenols, epigallocatechin-O-gallate (EGCg) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG), in a model digestive system at low oxygen tension with and without added digestive components and foods. Both compounds were stable at pH values of 5–6 and below, indicating gastric stability. Both compounds decomposed at pH 7.0. PGG was stabilized in a model system containing pepsin, pancreatin, bile and lipase, and/or baby food, but was not stabilized by dry cereal. EGCg was not stabilized by the addition of any biomolecule. The effects of polyphenols on human health should be evaluated in the context of their stability in the digestive tract with and without added digestive components and/or food. PMID:23028206

Emulsifying Properties of Oxidatively Stressed Myofibrillar Protein Emulsion Gels Prepared with (-)-Epigallocatechin-3-gallate and NaCl.

PubMed

Feng, Xianchao; Chen, Lin; Lei, Na; Wang, Shuangxi; Xu, Xinglian; Zhou, Guanghong; Li, Zhixi

2017-04-05

The dose-dependent effects of (-)-epigallocatechin-3-gallate (EGCG; 0, 100, or 1000 ppm) on the textural properties and stability of a myofibrillar protein (MP) emulsion gel were investigated. Addition of EGCG significantly inhibited formation of carbonyl but promoted the loss of both thiol and free amine groups. Addition of EGCG, particularly at 1000 ppm, initiated irreversible protein modifications, as evidenced by surface hydrophobicity changes, patterns in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and differential scanning calorimetry. These results indicated that MP was modified by additive reactions between the quinone of EGCG and thiols and free amines of proteins. These adducts increased cooking loss and destabilized the texture, especially with a large EGCG dose. Confocal laser scanning microscopy and scanning electron microscopy images clearly indicated the damage to the emulsifying properties and the collapse of the internal structure when the MP emulsion gel was treated with a large EGCG dose. A high concentration of NaCl (0.6 M) improved modification of MP and increased the rate of deterioration of the internal structure, especially with the large EGCG dose (1000 ppm), resulting in an MP emulsion gel with extremely unstable emulsifying properties.

Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

PubMed

Stringer, Megan; Abeysekera, Irushi; Thomas, Jared; LaCombe, Jonathan; Stancombe, Kailey; Stewart, Robert J; Dria, Karl J; Wallace, Joseph M; Goodlett, Charles R; Roper, Randall J

2017-08-01

Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis

Tea component, epigallocatechin gallate, potentiates anticataleptic and locomotor-sensitizing effects of caffeine in mice.

PubMed

Kasture, Sanjay B; Gaikar, Mayur; Kasture, Veena; Arote, Sanjay; Salve, Balu; Rosas, Michela; Cotti, Elisabetta; Acquas, Elio

2015-02-01

Tea is the most popular beverage worldwide. Caffeine, the psychoactive principle of tea, pharmacologically interacts with several drugs and bioactive molecules. Epigallocatechin gallate (EGCG) is a major component of tea and its known interactions with caffeine make it worthwhile to further study them by investigating the influence of EGCG on the anticataleptic and locomotor-sensitizing effects of caffeine. In the present investigation, we observed that (a) administration of caffeine or EGCG alone inhibited haloperidol-induced catalepsy, a widely used animal model to study parkinsonism, and (b) a combination of caffeine and EGCG produced greater inhibition of haloperidol-induced catalepsy. Furthermore, after repeated administration of caffeine and EGCG, either alone or in combination, we observed that (c) caffeine and EGCG contrasted the sensitization of catalepsy observed after repeated haloperidol administration by significantly reducing the duration of catalepsy. Furthermore, as haloperidol-induced catalepsy was also associated with increased lipid peroxidation, we observed that (d) EGCG administration reduced striatal lipid peroxide levels in a dose-dependent manner and that (e) the combination of caffeine with EGCG was most effective in reducing haloperidol-increased striatal lipid peroxide. Finally, we observed that (f) chronic caffeine and EGCG significantly elicited locomotor sensitization and that (g) their combination resulted in significantly greater effects. In conclusion, EGCG potentiated the effects of caffeine on haloperidol-induced catalepsy and of caffeine-elicited locomotor sensitization. Overall, these observations indicate critical interactions between caffeine and EGCG in an animal model of parkinsonism and locomotor activity and suggest that tea consumption might reduce antipsychotic-induced side effects.

Green tea (-)-epigallocatechin-3-gallate counteracts daytime overeating induced by high-fat diet in mice.

PubMed

Li, Hongyu; Kek, Huiling Calvina; Lim, Joy; Gelling, Richard Wayne; Han, Weiping

2016-12-01

High-fat diet (HFD) induces overeating and obesity. Green tea (-)-epigallocatechin-3-gallate (EGCG) reduces HFD-induced body weight and body fat gain mainly through increased lipid metabolism and fat oxidation. However, little is known about its effect on HFD-induced alterations in feeding behavior. Three diet groups of wildtype C57B/6j male mice at 5 months old were fed on normal chow diet, 1 week of HFD (60% of energy) and 3 months of HFD (diet-induced obesity (DIO)) prior to EGCG supplement in respective diet. EGCG had no effect on feeding behavior in normal chow diet group. Increased daytime feeding induced by HFD was selectively corrected by EGCG treatment in HFD groups, including reversed food intake, feeding frequency and meal size in HFD + EGCG group, and reduced food intake and feeding frequency in DIO + EGCG group. Moreover, EGCG treatment altered diurnally oscillating expression pattern of key appetite-regulating genes, including AGRP, POMC, and CART, and key circadian genes Clock and Bmal1 in hypothalamus of DIO mice, indicating its central effect on feeding regulation. Our study demonstrates that EGCG supplement specifically counteracts daytime overeating induced by HFD in mice, suggesting its central role in regulating feeding behavior and energy homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biophysical characteristics of proteins and living cells exposed to the green tea polyphenol epigallocatechin-3-gallate (EGCg): review of recent advances from molecular mechanisms to nanomedicine and clinical trials.

PubMed

Peter, Beatrix; Bosze, Szilvia; Horvath, Robert

2017-01-01

Herbs and traditional medicines have been applied for thousands of years, but researchers started to study their mode of action at the molecular, cellular and tissue levels only recently. Nowadays, just like in ancient times, natural compounds are still determining factors in remedies. To support this statement, the recently won Nobel Prize for an anti-malaria agent from the plant sweet wormwood, which had been used to effectively treat the disease, could be mentioned. Among natural compounds and traditional Chinese medicines, the green tea polyphenol epigallocatechin gallate (EGCg) is one of the most studied active substances. In the present review, we summarize the molecular scale interactions of proteins and EGCg with special focus on its limited stability and antioxidant properties. We outline the observed biophysical effects of EGCg on various cell lines and cultures. The alteration of cell adhesion, motility, migration, stiffness, apoptosis, proliferation as well as the different impacts on normal and cancer cells are all reviewed. We also handle the works performed using animal models, microbes and clinical trials. Novel ways to develop its utilization for therapeutic purposes in the future are discussed too, for instance, using nanoparticles and green tea polyphenols together to cure illnesses and the combination of EGCg and anticancer compounds to intensify their effects. The limitations of the employed experimental models and criticisms of the interpretation of the obtained experimental data are summarized as well.

Hippocampal Neuroprotection by Minocycline and Epigallo-Catechin-3-Gallate Against Cardiopulmonary Bypass-Associated Injury.

PubMed

Salameh, Aida; Einenkel, Anne; Kühne, Lydia; Grassl, Maria; von Salisch, Sandy; Kiefer, Phillip; Vollroth, Marcel; Dähnert, Ingo; Dhein, Stefan

2015-11-01

Surgical correction of congenital cardiac malformations mostly implies the use of cardiopulmonary bypass (CPB). However, a possible negative impact of CPB on cerebral structures like the hippocampus cannot be neglected. Therefore, we investigated the effect of CPB on hippocampus CA1 and CA3 regions without or with the addition of epigallocatechin-3-gallate (EGCG) or minocycline. We studied 42 piglets and divided them into six experimental groups: control without or with EGCG or minocycline, CPB without or with EGCG or minocycline. The piglets underwent 90 minutes CPB and subsequently, a 120-minute recovery and reperfusion phase. Thereafter, histology of the hippocampus was performed and the adenosine triphosphate (ATP) content was measured. Histologic evaluation revealed that CPB produced a significant peri-cellular edema in both CA regions. Moreover, we found an increased number of cells stained with markers for hypoxia, apoptosis and nitrosative stress. Most of these alterations were significantly reduced to or near to control levels by application of EGCG or minocycline. ATP content was significantly reduced within the hippocampus after CPB. This reduction could not be antagonized by EGCG or minocycline. In conclusion, CPB had a significant negative impact on the integrity of hippocampal neural cells. This cellular damage could be significantly attenuated by addition of EGCG or minocycline. © 2015 International Society of Neuropathology.

Epigallocatechin-3-gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing.

PubMed

Li, Min; Xu, Jingxing; Shi, Tongxin; Yu, Haiyang; Bi, Jianping; Chen, Guanzhi

2016-11-01

In non-healing wounds, mesenchymal stem cell (MSC)-based therapies have the potential to activate a series of coordinated cellular processes, including angiogenesis, inflammation, cell migration, proliferation and epidermal terminal differentiation. As pro-inflammatory reactions play indispensable roles in initiating wound repair, sustained and prolonged inflammation exhibit detrimental effects on skin wound closure. We investigated the feasibility of using an antioxidant agent epigallocatechin-3-gallate (EGCG), along with MSCs, to improve wound repair through their immunomodulatory actions. In a rat model of wound healing, a single dose of EGCG at 10 mg/kg increased the efficiency of MSC-induced skin wound closure. Twenty days after the wound induction, MSC treatment significantly enhanced the epidermal thickness, which was further increased by EGCG administration. Consistently, the highest extent of growth factors upregulation for neovascularization induction was seen in the animals treated by both MSCs and EGCG, associated with a potent anti-scarring effect throughout the healing process. Finally, expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6, in the wound area were reduced by MSCs, and this reduction was further potentiated by EGCG co-administration. EGCG, together with MSCs, can promote skin wound healing likely through their combinational effects in modulating chronic inflammation. © 2016 John Wiley & Sons Australia, Ltd.

Evaluation of unsaturated alkanoic acid amides as maskers of epigallocatechin gallate astringency.

PubMed

Obst, Katja; Paetz, Susanne; Backes, Michael; Reichelt, Katharina V; Ley, Jakob P; Engel, Karl-Heinz

2013-05-08

Some foods, beverages, and food ingredients show characteristic long-lasting aftertastes. The sweet, lingering taste of high intensity sweeteners or the astringency of tea catechins are typical examples. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, causes a long-lasting astringency and bitterness. These sensations are mostly perceived as aversive and are only accepted in a few foods (e.g., tea and red wine). For the evaluation of the aftertaste of such constituents over a certain period of time, Intensity Variation Descriptive Methodology (IVDM) was used. The approach allows the measurement of different descriptors in parallel in one panel session. IVDM was evaluated concerning the inter- and intraindividual differences of panelists for bitterness and astringency of EGCG. Subsequently, the test method was used as a screening tool for the identification of potential modality-selective masking compounds. In particular, the intensity of the astringency of EGCG (750 mg kg(-1)) could be significantly lowered by 18-33% during the time course by adding the trigeminal-active compound trans-pellitorine (2E,4E-decadienoic acid N-isobutyl amide 1, 5 mg kg(-1)) without significantly affecting bitterness perception. Further, structurally related compounds were evaluated on EGCG to gain evidence for possible structure-activity relationships. A more polar derivative of 1, (2S)-2-[[(2E,4E)-deca-2,4-dienoyl]amino]propanoic acid 9, was also able to reduce the astringency of EGCG similar to trans-pellitorine but without showing the strong tingling effect.

Epigallocatechin-3-Gallate Ameliorates Glucocorticoid-Induced Osteoporosis of Rats in Vivo and in Vitro.

PubMed

Liu, Shengye; Yang, Liyu; Mu, Shuai; Fu, Qin

2018-01-01

Background: Prolonged administration of overdoses of glucocorticoids results in increased bone remodeling, leading to glucocorticoid-induced osteoporosis (GIO), which is primarily due to the dysfunction and apoptosis of osteoblasts. The present study investigated the therapeutic effect and molecular mechanism of action of epigallocatechin-3-gallate (EGCG), a bioactive catechin in green tea, in high-dose dexamethasone-induced osteoblast differentiation in vivo and in vitro . Methods: The anti-dexamethasone (DEX) effects of EGCG on primary osteoblasts were determined on the basis of cell viability and alkaline phosphatase (ALP) and total cellular superoxide dismutase (SOD) activities. Flow cytometry and Western blot analysis were also used to evaluate the expression of related biomarkers in vitro , and bone microarchitecture was also extensively examined in a rat model in vivo . Results: The results showed that EGCG pretreatment significantly increased osteoblast viability and ALP and SOD activities when cells were exposed to DEX. Alizarin red staining indicated that there was more mineralization with EGCG pretreatment, countering DEX effects. EGCG reduced DEX-induced reactive oxygen species at both the mitochondrial and cellular levels in osteoblasts by activating the nuclear factor erythroid-derived 2-like-2 (Nrf2) pathway. In addition, EGCG protected osteoblasts from apoptosis. EGCG also regulated the formation of active glucocorticoid by 11β-hydroxysteroid dehydrogenase activity. Furthermore, femoral micro-computed tomography scans revealed that EGCG improved bone microstructure and mitigated DEX-induced deterioration of bone quality. Conclusion: These findings suggested that EGCG reversed GIO in rats by protecting osteoblasts by activating the Nrf2 signaling pathway.

Epigallocatechin-3-gallate protects Kuruma shrimp Marsupeneaus japonicus from white spot syndrome virus and Vibrio alginolyticus.

PubMed

Wang, Zhi; Sun, Baozhen; Zhu, Fei

2018-07-01

Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and exhibits potential antibacterial and anticancer activities. In this study, EGCG was used in pathogen-challenge experiments in shrimp to discover its effect on the innate immune system of an invertebrate. Kuruma shrimp Marsupeneaus japonicus was used as an experimental model and challenged with white spot syndrome virus (WSSV) and the Gram-negative bacterium Vibrio alginolyticus. Pathogen-challenge experiments showed that EGCG pretreatment significantly delayed and reduced mortality upon WSSV and V. alginolyticus infection, with VP-28 copies of WSSV also reduced. Quantitative reverse transcription polymerase chain reaction revealed the positive influence of EGCG on several innate immune-related genes, including IMD, proPO, QM, myosin, Rho, Rab7, p53, TNF-alpha, MAPK, and NOS, and we observed positive influences on three immune parameters, including total hemocyte count and phenoloxidase and superoxide dismutase activities, by EGCG treatment. Additionally, results showed that EGCG treatment significantly reduced apoptosis upon V. alginolyticus challenge. These results indicated the positive role of EGCG in the shrimp innate immune system as an enhancer of immune parameters and an inhibitor of apoptosis, thereby delaying and reducing mortality upon pathogen challenge. Our findings provide insight into potential therapeutic or preventive functions associated with EGCG to enhance shrimp immunity and protect shrimp from pathogen infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats

PubMed Central

Alway, Stephen E.; Bennett, Brian T.; Wilson, Joseph C.; Edens, Neile K.; Pereira, Suzette L.

2014-01-01

Aging exacerbates muscle loss and slows the recovery of muscle mass and function after disuse. In this study we investigated the potential that epigallocatechin gallate (EGCg), an abundant catechin in green tea, would reduce signaling for apoptosis and promote skeletal muscle recovery in the fast plantaris muscle and the slow soleus muscle after hindlimb unloading (HLS) in senescent animals. Fischer 344 × Brown Norway inbred rats (age 34 mo.) received either EGCg (50 mg/kg body weight), or water daily by gavage. One group of animals received HLS for 14 days and a second group of rats received 14 days of HLS, then the HLS was removed and they recovered from this forced disuse for 2 weeks. Animals that received EGCg over the HLS followed by 14 days of recovery, had a 14% greater plantaris muscle weight (p <0.05) as compared to the animals treated with the vehicle over this same period. Plantaris fiber area was greater after recovery in EGCg (2715.2 ± 113.8 μm2) vs. vehicle treated animals (1953.0 ± 41.9 μm2). In addition, activation of myogenic progenitor cells was improved with EGCg over vehicle treatment (7.5% vs. 6.2%) in the recovery animals. Compared to vehicle treatment, the apoptotic index was lower (0.24% vs. 0.52%), and the abundance of pro-apoptotic proteins Bax (−22%), and FADD (−77%) were lower in EGCg treated plantaris muscles after recovery. While EGCg did not prevent unloading-induced atrophy, it improved muscle recovery after the atrophic stimulus in fast plantaris muscles. However, this effect was muscle specific because EGCg had no major impact in reversing HLS-induced atrophy in the slow soleus muscle of old rats. PMID:24316035

Epigallocatechin gallate attenuates experimental non-alcoholic steatohepatitis induced by high fat diet.

PubMed

Kuzu, Nalan; Bahcecioglu, Ibrahim Halil; Dagli, Adile Ferda; Ozercan, Ibrahim Hanifi; Ustündag, Bilal; Sahin, Kazim

2008-08-01

In the present study, we examined the preventive role of epigallocatechin gallate (EGCG) in an experimental non-alcoholic steatohepatitis model induced by a high fat diet. The study included 21 male Sprague-Dawley rats, which were equally divided into three groups. The first group was fed on a standard rat diet, the second group on a high fat diet (HFD), and the third group on a HFD + EGCG. The study concluded after 6 weeks. Histopathological examination was performed. Plasma and tissue MDA levels, glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, triglyceride, and cholesterol levels were studied. Insulin resistance was calculated by the homeostasis model of insulin resistance method. Steatosis, inflammation, ballooning degeneration, and necrosis increased significantly in the HFD group, compared to the control group (P < 0.01). Steatosis and inflammation decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.05, for each). There was a significant decline in ALT (P < 0.01), triglyceride (P < 0.01), insulin (P < 0.05), and glucose (P < 0.05) levels in the HFD + EGCG group, when compared to the HFD group. Plasma and liver MDA levels in the HFD + EGCG group were lower than those of the HFD group; the difference was significant (P < 0.01 for each). Glutathione levels in the HFD + EGCG group was significantly higher those in the HFD group. CYP 2E1 and alpha-smooth muscle actin expression decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.01, P < 0.05, respectively). EGCG reduces the development of experimental non-alcoholic steatohepatitis induced by a high fat diet. It seems to exercise this effect through its effect on lipid metabolism and antioxidant characteristics.

Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats.

PubMed

Alway, Stephen E; Bennett, Brian T; Wilson, Joseph C; Edens, Neile K; Pereira, Suzette L

2014-02-01

Aging exacerbates muscle loss and slows the recovery of muscle mass and function after disuse. In this study we investigated the potential that epigallocatechin-3-gallate (EGCg), an abundant catechin in green tea, would reduce signaling for apoptosis and promote skeletal muscle recovery in the fast plantaris muscle and the slow soleus muscle after hindlimb suspension (HLS) in senescent animals. Fischer 344 × Brown Norway inbred rats (age 34 months) received either EGCg (50 mg/kg body weight), or water daily by gavage. One group of animals received HLS for 14 days and a second group of rats received 14 days of HLS, then the HLS was removed and they recovered from this forced disuse for 2 weeks. Animals that received EGCg over the HLS followed by 14 days of recovery, had a 14% greater plantaris muscle weight (p<0.05) as compared to the animals treated with the vehicle over this same period. Plantaris fiber area was greater after recovery in EGCg (2715.2±113.8 μm(2)) vs. vehicle treated animals (1953.0±41.9 μm(2)). In addition, activation of myogenic progenitor cells was improved with EGCg over vehicle treatment (7.5% vs. 6.2%) in the recovery animals. Compared to vehicle treatment, the apoptotic index was lower (0.24% vs. 0.52%), and the abundance of pro-apoptotic proteins Bax (-22%), and FADD (-77%) was lower in EGCg treated plantaris muscles after recovery. While EGCg did not prevent unloading-induced atrophy, it improved muscle recovery after the atrophic stimulus in fast plantaris muscles. However, this effect was muscle specific because EGCg had no major impact in reversing HLS-induced atrophy in the slow soleus muscle of old rats. Copyright © 2013 Elsevier Inc. All rights reserved.

Epigallocatechin-3-gallate (EGCG) up-regulates miR-15b expression thus attenuating store operated calcium entry (SOCE) into murine CD4+ T cells and human leukaemic T cell lymphoblasts.

PubMed

Zhang, Shaqiu; Al-Maghout, Tamer; Bissinger, Rosi; Zeng, Ni; Pelzl, Lisann; Salker, Madhuri S; Cheng, Anchun; Singh, Yogesh; Lang, Florian

2017-10-27

CD4 + T cells are key elements in immune responses and inflammation. Activation of T cell receptors in CD4 + T cells triggers cytosolic Ca 2+ release with subsequent store operated Ca 2+ entry (SOCE), which is accomplished by the pore forming Ca 2+ release activated Ca 2+ (CRAC) channel Orai1 and its regulator stromal cell-interaction molecule 2 (STIM2). Green tea polyphenol epigallocatechin-3-gallate (EGCG) acts as a potent anti-inflammatory and anti-oxidant agent for various types of cells including immune cells. However, how post-transcriptional gene regulators such as miRNAs are involved in the regulation of Ca 2+ influx into murine CD4 + T cells and human Jurkat T cells through EGCG is not defined. EGCG treatment of murine CD4 + T cells significantly down-regulated the expression of STIM2 and Orai1 both at mRNA and protein levels. Furthermore, EGCG significantly decreased SOCE in both murine and human T cells. EGCG treatment increased miRNA-15b (miR-15b) abundance in both murine and human T cells. Bioinformatics analysis reveals that miR-15b, which has a STIM2 binding site, is involved in the down-regulation of SOCE. Overexpression of miR-15b significantly decreased the mRNA and protein expression of STIM2 and Orai1 in murine T cells. Treatment of Jurkat T cells with 10 μM EGCG further decreased mTOR and PTEN protein levels. EGCG decreased mitochondrial membrane potential (MMP) in both human and murine T cells. In conclusion, the observations suggest that EGCG inhibits the Ca 2+ entry into murine and human T cells, an effect accomplished at least in part by up-regulation of miR-15b.

Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia.

PubMed

Ramachandran, Balaji; Jayavelu, Subramani; Murhekar, Kanchan; Rajkumar, Thangarajan

2016-01-01

EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

Epigallocatechin 3-gallate inhibits 7-ketocholesterol-induced monocyte-endothelial cell adhesion.

PubMed

Yamagata, Kazuo; Tanaka, Noriko; Suzuki, Koichi

2013-07-01

7-Ketocholesterol (7KC) induces monocytic adhesion to endothelial cells, and induces arteriosclerosis while high-density lipoprotein (HDL) inhibits monocytic adhesion to the endothelium. Epigallocatechin 3-gallate (EGCG) was found to have a protective effect against arteriosclerosis. Therefore, the purpose of this study was to examine the possible HDL-like mechanisms of EGCG in endothelial cells by investigating whether EGCG inhibits 7KC-induced monocyte-endothelial cell adhesion by activating HDL-dependent signal transduction pathways. 7KC and/or EGCG were added to human endothelial cells (ISO-HAS), and the adhesion of pro-monocytic U937 cells was examined. The expression of genes associated with HDL effects such as Ca(2+)/calmodulin-dependent kinase II (CaMKKII), liver kinase B (LKD1), PSD-95/Dlg/ZO-1 kinase 1 (PDZK1), phosphatidylinositol 3-kinase (PI3K), intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1), and endothelial nitric oxide synthase (eNOS) was examined by RT-PCR, and ICAM-1 protein expression was evaluated by western blot (WB). Production of reactive oxygen species (ROS) was examined with H2DCFDA. 7KC significantly induced adhesion of U937 cells to human endothelial cells while significantly increasing gene expressions of ICAM-1 and MCP-1 and decreasing eNOS and CaMKKII gene expressions. EGCG inhibited 7KC-induced monocytic adhesion to endothelial cells, and induced expression of eNOS and several genes involved in the CaMKKII pathway. Stimulation of endothelial cells with EGCG produced intracellular ROS, whereas treatment with N-acetylcysteine (NAC) blocked EGCG-induced expression of eNOS and CaMKKII. These results suggest that inhibition of monocyte-endothelial cell adhesion by EGCG is associated with CaMKKII pathway activation by ROS. Inhibition of 7KC-induced monocyte-endothelial cell adhesion induced by EGCG may function similarly to HDL. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of continuous phase protein, (-)-epigallocatechin-3-gallate and carrier oil on β-carotene degradation in oil-in-water emulsions.

PubMed

Liu, Lei; Gao, Yanxiang; McClements, David Julian; Decker, Eric Andrew

2016-11-01

The chemical instability of β-carotene limits its utilization as a nutraceutical ingredient in foods. In this research, the effect of continuous phase alpha-lactalbumin (α-LA) and (-)-epigallocatechin-3-gallate (EGCG) on β-carotene degradation in medium chain triacylglycerol (MCT)- and corn oil-in-water emulsions was examined. EGCG significantly inhibited β-carotene degradation in both MCT and corn oil-in-water emulsions in a dose dependent manner. α-LA was not able to protect β-carotene in MCT emulsions and the combination of EGCG and α-LA had a similar effect as EGCG alone. EGCG had no effect on lipid oxidation in corn oil-in-water emulsions but can protect β-carotene. β-Carotene was more stable in corn oil emulsions stabilized by α-LA compared to emulsions stabilized by Tween 20. These results show that EGCG is effective at protecting β-carotene in different emulsion systems without negatively impacting lipid oxidation suggesting that it could be utilized to increase the incorporation of β-carotene into food emulsions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation of epigallocatechin gallate-loaded nanoparticles and characterization of their inhibitory effects on Helicobacter pylori growth in vitro and in vivo

NASA Astrophysics Data System (ADS)

Lin, Yu-Hsin; Feng, Chun-Lung; Lai, Chih-Ho; Lin, Jui-Hsiang; Chen, Hao-Yun

2014-08-01

A variety of approaches have been proposed for overcoming the unpleasant side effects associated with antibiotics treatment of Helicobacter pylori (H. pylori) infections. Research has shown that epigallocatechin-3-gallate (EGCG), a major ingredient in green tea, has antibacterial activity for antiurease activity against H. pylori. Oral EGCG is not good because of its digestive instability and the fact that it often cannot reach the targeted site of antibacterial activity. To localize EGCG to H. pylori infection site, this study developed a fucose-chitosan/gelatin nanoparticle to encapsulate EGCG at the target and make direct contact with the region of microorganisms on the gastric epithelium. Analysis of a simulated gastrointestinal medium indicated that the proposed in vitro nanocarrier system effectively controls the release of EGCG, which interacts directly with the intercellular space at the site of H. pylori infection. Meanwhile, results of in vivo clearance assays indicated that our prepared fucose-chitosan/gelatin/EGCG nanoparticles had a significantly greater H. pylori clearance effect and more effectively reduced H. pylori-associated gastric inflammation in the gastric-infected mouse model than the EGCG solution alone.

Physicochemical characterisation of β-carotene emulsion stabilised by covalent complexes of α-lactalbumin with (-)-epigallocatechin gallate or chlorogenic acid.

PubMed

Wang, Xiaoya; Liu, Fuguo; Liu, Lei; Wei, Zihao; Yuan, Fang; Gao, Yanxiang

2015-04-15

In this study the impact of covalent complexes of α-lactalbumin (α-La) with (-)-epigallocatechin gallate (EGCG) or chlorogenic acid (CA) was investigated on the physicochemical properties of β-carotene oil-in-water emulsions. EGCG, or CA, was covalently linked to α-La at pH 8.0, as evidenced by increased total phenolic content and declined fluorescence intensity. Compared with those stabilised by α-La alone and α-La-CA or EGCG mixture, the emulsion stabilised by the α-La-EGCG covalent complex exhibited the least changes in particle size and transmission profiles, using a novel centrifugal sedimentation technique, indicating an improvement in the physical stability. The least degradation of β-carotene occurred in the emulsion stabilised with the α-La-EGCG covalent complex when stored at 25 °C. These results implied that protein-polyphenol covalent complexes were able to enhance the physical stability of β-carotene emulsion and inhibit the degradation of β-carotene in oil-in-water emulsion, and the effect was influenced by the types of the phenolic compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prevention of carcinogenesis of mouse mammary epithelial cells RIII/MG by epigallocatechin gallate.

PubMed

Yanaga, Hiroshi; Fujii, Teruhiko; Koga, Toshihiro; Araki, Ruriko; Shirouzu, Kazuo

2002-09-01

The chemopreventive effect of the polyphenols abundant in green tea on carcinogenesis has been attracting attention in recent years. Among tea polyphenols, epigallocatechin gallate (EGCG) has been studied as a preventive substance for carcinogenesis. We investigated the chemopreventive effect in a group treated with EGCG in vitro and in vivo using mouse mammary epithelial cells RIII/MG. In the in vitro experiment, crude catechin (catechin) containing 50% or more EGCG significantly inhibited the growth of RIII/MG cells, which were precancerous cultured cells. Many cells died, and a DNA ladder was observed. In the in vivo experiment, RIII/MG cells formed a tumor after 13 weeks in a group without catechin treatment, and the tumor formation rate in the 20th week was 40%. In a group treated with 0.1% catechin, a tumor began to grow in the 13th week, and the tumor formation rate in the 20th week was 20%. In a group treated with 1% catechin, no tumor was detected even in the 20th week. There was no significant difference in the change in body weight between the catechin treatment groups and the non-treatment group during the observation period. Tissue samples were stained by the nick-end-labeling method and apoptosis was observed in many cells. Based on the above findings, EGCG inhibited growth in the mouse viral mammary epithelial carcinogenesis model RIII/MG, and induced apoptosis, suggesting a clinical usefulness of EGCG as a chemopreventive substance.

Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity

PubMed Central

Borse, Vikrant; Al Aameri, Raheem F H; Sheehan, Kelly; Sheth, Sandeep; Kaur, Tejbeer; Mukherjea, Debashree; Tupal, Srinivasan; Lowy, Michelle; Ghosh, Sumana; Dhukhwa, Asmita; Bhatta, Puspanjali; Rybak, Leonard P; Ramkumar, Vickram

2017-01-01

Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent. Rats administered oral EGCG demonstrate reduced cisplatin-induced hearing loss, reduced loss of OHCs in the basal region of the cochlea and reduced oxidative stress and apoptotic markers. EGCG also protected against the loss of ribbon synapses associated with inner hair cells and Na+/K+ ATPase α1 in the stria vascularis and spiral ligament. In vitro studies showed that EGCG reduced cisplatin-induced ROS generation and ERK1/2 and signal transducer and activator of transcription-1 (STAT1) activity, but preserved the activity of STAT3 and Bcl-xL. The increase in STAT3/STAT1 ratio appears critical for mediating its otoprotection. EGCG did not alter cisplatin-induced apoptosis of human-derived cancer cells or cisplatin antitumor efficacy in a xenograft tumor model in mice because of its inability to rescue the downregulation of STAT3 in these cells. These data suggest that EGCG is an ideal otoprotective agent for treating cisplatin-induced hearing loss without compromising its antitumor efficacy. PMID:28703809

Transcriptomic analysis of the response of Pseudomonas fluorescens to epigallocatechin gallate by RNA-seq

PubMed Central

Liu, Xiaoxiang; Shen, Bimiao; Du, Peng; Wang, Nan; Wang, Jiaxue; Li, Jianrong

2017-01-01

Epigallocatechin gallate (EGCG) is a main constituent of green tea polyphenols that are widely used as food preservatives and are considered to be safe for consumption. However, the underlying antimicrobial mechanism of EGCG and the bacterial response to EGCG are not clearly understood. In the present study, a genome-wide transcriptional analysis of a typical spoilage bacterium, Pseudomonas fluorescens that responded to EGCG was performed using RNA-seq technology. A total of 26,365,414 and 23,287,092 clean reads were generated from P. fluorescens treated with or without 1 mM EGCG and the clean reads were aligned to the reference genome. Differential expression analysis revealed 291 upregulated genes and 134 downregulated genes and the differentially expressed genes (DEGs) were verified using RT-qPCR. Most of the DGEs involved in iron uptake, antioxidation, DNA repair, efflux system, cell envelope and cell-surface component synthesis were significantly upregulated by EGCG treatment, while most genes associated with energy production were downregulated. These transcriptomic changes are likely to be adaptive responses of P. fluorescens to iron limitation and oxidative stress, as well as DNA and envelope damage caused by EGCG. The expression of specific genes encoding the extra-cytoplasmic function sigma factor (PvdS, RpoE and AlgU) and the two-component sensor histidine kinase (BaeS and RpfG) were markedly changed by EGCG treatment, which may play important roles in regulating the stress responses of P. fluorescens to EGCG. The present data provides important insights into the molecular action of EGCG and the possible cross-resistance mediated by EGCG on P. fluorescens, which may ultimately contribute to the optimal application of green tea polyphenols in food preservation. PMID:28545064

Epigallocatechin-3-gallate protects against hepatic ischaemia-reperfusion injury by reducing oxidative stress and apoptotic cell death.

PubMed

Tak, Eunyoung; Park, Gil-Chun; Kim, Seok-Hwan; Jun, Dae Young; Lee, Jooyoung; Hwang, Shin; Song, Gi-Won; Lee, Sung-Gyu

2016-12-01

Objective To investigate the protective effects of epigallocatechin-3-gallate (EGCG), a major polyphenol source in green tea, against hepatic ischaemia-reperfusion injury in mice. Methods The partial hepatic ischaemia-reperfusion injury model was created by employing the hanging-weight method in C57BL/6 male mice. EGCG (50 mg/kg) was administered via an intraperitoneal injection 45 min before performing the reperfusion. A number of markers of inflammation, oxidative stress, apoptosis and liver injury were measured after the ischaemia-reperfusion injury had been induced. Results The treatment groups were: sham-operated (Sham, n = 10), hepatic ischaemia-reperfusion injury (IR, n = 10), and EGCG with ischaemia-reperfusion injury (EGCG-treated IR, n = 10). Hepatic ischaemia-reperfusion injury increased the levels of biochemical and histological markers of liver injury, increased the levels of malondialdehyde, reduced the glutathione/oxidized glutathione ratio, increased the levels of oxidative stress and lipid peroxidation markers, decreased B-cell lymphoma 2 levels, and increased the levels of Bax, cytochrome c, cleaved caspase-3, and cleaved caspase-9. Pretreatment with EGCG ameliorated all of these changes. Conclusion The antioxidant and antiapoptotic effects of EGCG protected against hepatic ischaemia-reperfusion injury in mice.

Epigallocatechin-3-gallate protects against hepatic ischaemia–reperfusion injury by reducing oxidative stress and apoptotic cell death

PubMed Central

Tak, Eunyoung; Park, Gil-Chun; Kim, Seok-Hwan; Jun, Dae Young; Lee, Jooyoung; Hwang, Shin; Lee, Sung-Gyu

2016-01-01

Objective To investigate the protective effects of epigallocatechin-3-gallate (EGCG), a major polyphenol source in green tea, against hepatic ischaemia–reperfusion injury in mice. Methods The partial hepatic ischaemia–reperfusion injury model was created by employing the hanging-weight method in C57BL/6 male mice. EGCG (50 mg/kg) was administered via an intraperitoneal injection 45 min before performing the reperfusion. A number of markers of inflammation, oxidative stress, apoptosis and liver injury were measured after the ischaemia–reperfusion injury had been induced. Results The treatment groups were: sham-operated (Sham, n = 10), hepatic ischaemia–reperfusion injury (IR, n = 10), and EGCG with ischaemia–reperfusion injury (EGCG-treated IR, n = 10). Hepatic ischaemia–reperfusion injury increased the levels of biochemical and histological markers of liver injury, increased the levels of malondialdehyde, reduced the glutathione/oxidized glutathione ratio, increased the levels of oxidative stress and lipid peroxidation markers, decreased B-cell lymphoma 2 levels, and increased the levels of Bax, cytochrome c, cleaved caspase-3, and cleaved caspase-9. Pretreatment with EGCG ameliorated all of these changes. Conclusion The antioxidant and antiapoptotic effects of EGCG protected against hepatic ischaemia–reperfusion injury in mice. PMID:27807255

Epigallocatechin gallate inhibits Streptococcus pneumoniae virulence by simultaneously targeting pneumolysin and sortase A.

PubMed

Song, Meng; Teng, Zihao; Li, Meng; Niu, Xiaodi; Wang, Jianfeng; Deng, Xuming

2017-10-01

Streptococcus pneumoniae (pneumococcus), the causative agent of several human diseases, possesses numerous virulence factors associated with pneumococcal infection and pathogenesis. Pneumolysin (PLY), an important virulence factor, is a member of the cholesterol-dependent cytolysin family and has cytolytic activity. Sortase A (SrtA), another crucial pneumococcal virulence determinate, contributes greatly to the anchoring of many virulence-associated surface proteins to the cell wall. In this study, epigallocatechin gallate (EGCG), a natural compound with little known antipneumococcal activity, was shown to directly inhibit PLY-mediated haemolysis and cytolysis by blocking the oligomerization of PLY and simultaneously reduce the peptidase activity of SrtA. The biofilm formation, production of neuraminidase A (NanA, the pneumococcal surface protein anchored by SrtA), and bacterial adhesion to human epithelial cells (Hep2) were inhibited effectively when S. pneumoniae D39 was cocultured with EGCG. The results from molecular dynamics simulations and mutational analysis confirmed the interaction of EGCG with PLY and SrtA, and EGCG binds to Glu277, Tyr358, and Arg359 in PLY and Thr169, Lys171, and Phe239 in SrtA. In vivo studies further demonstrated that EGCG protected mice against S. pneumoniae pneumonia. Our results imply that EGCG is an effective inhibitor of both PLY and SrtA and that an antivirulence strategy that directly targets PLY and SrtA using EGCG is a promising therapeutic option for S. pneumoniae pneumonia. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

A new update for radiocontrast-induced nephropathy aggravated with glycerol in rats: the protective potential of epigallocatechin-3-gallate

PubMed Central

Palabiyik, Saziye Sezin; Dincer, Busra; Cadirci, Elif; Cinar, Irfan; Gundogdu, Cemal; Polat, Beyzagul; Yayla, Muhammed; Halici, Zekai

2017-01-01

Abstract Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms. PMID:28100100

Effect of particle size in preparative reversed-phase high-performance liquid chromatography on the isolation of epigallocatechin gallate from Korean green tea.

PubMed

Kim, Jung Il; Hong, Seung Bum; Row, Kyung Ho

2002-03-08

To isolate epigallocatechin gallate (EGCG) of catechin compounds from Korean green tea (Bosung, Chonnam), a C18 reversed-phase preparative column (250x22 mm) packed with packings of three different sizes (15, 40-63, and 150 microm) was used. The sample extracted with water was partitioned with chloroform and ethyl acetate to remove the impurities including caffeine. The mobile phases in this experiment were composed of 0.1% acetic acid in water, acetonitrile, methanol and ethyl acetate. The injection volume was fixed at 400 microl and the flow rate was increased as the particle size becomes larger. The isolation of EGCG with particle size was compared at a preparative scale and the feasibility of separation of EGCG at larger particle sizes was confirmed. The optimum mobile phase composition for separating EGCG was experimentally obtained at the particle sizes of 15 and 40-63 microm in the isocratic mode, but EGCG was not purely separated at the particle size of 150 microm.

Effects of epigallocatechin gallate on lipid metabolism and its underlying molecular mechanism in broiler chickens.

PubMed

Huang, J B; Zhang, Y; Zhou, Y B; Wan, X C; Zhang, J S

2015-08-01

The objective of this study was to investigate the effects of epigallocatechin gallate (EGCG) on fat metabolism and to establish the molecular mechanism of these effects in broilers. Seventy-two 28-day-old male Ross 308 broiler chickens were divided into three groups with different levels of EGCG supplementation for 4 weeks: normal control (NC) group, L-EGCG (a low-level supplement of EGCG, 40 mg/kg body weight daily) and H-EGCG (a high-level supplement of EGCG, 80 mg/kg body weight daily). After 4 weeks of oral administration, EGCG significantly reduced the level of abdominal fat deposition in broilers. The serum triglycerides and low-density lipoprotein cholesterol of chickens in H-EGCG group were also significantly decreased compared with the NC group, and the high-density lipoprotein cholesterol was notably increased at the same time. Moreover, the vital role of the liver and abdominal adipose tissue in lipid metabolism of poultry animals was examined through gene expression and enzyme activities related to fat anabolism and catabolism in these organs. Our data show that EGCG supplementation for 2 weeks significantly downregulated the expression of fatty acid synthesis and fat deposition-related genes, and upregulated the expression of genes involved in fatty acid β-oxidation and lipolysis genes. Simultaneously, the activities of hepatic fatty acid synthesis enzymes (fatty acid synthase and acetyl CoA carboxylase) were significantly decreased, and the activity of carnitine palmitoyl transferase-1 was notably elevated. The results suggest that EGCG could alleviate fat deposition in broilers through inhibiting fat anabolism and stimulating lipid catabolism in broilers. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Green tea extract (epigallocatechin-3-gallate) reduces efficacy of radiotherapy on prostate cancer cells.

PubMed

Thomas, Francis; Holly, Jeff M P; Persad, Rajendra; Bahl, Amit; Perks, Claire M

2011-08-01

To assess the influence of epigallocatechin-3-gallate (EGCG) on the efficacy of ionizing radiation on prostate cancer cells because of the increased use of dietary interventions, especially by patients with prostate cancer. Radiotherapy is used to treat localized prostate cancer. Some people consume green tea (EGCG) as a chemopreventive agent against prostate cancer. Green tea can act as an antioxidant and induce superoxide dismutase enzymes, which could scavenge the free oxygen radicals generated by radiotherapy. Prostate cancer cell line DU145 cells were treated with EGCG or radiotherapy, or both. Cell death was assessed using trypan blue cell counting, and apoptosis was confirmed by assessing poly (adenosine phosphate ribose) polymerase cleavage. The antioxidant potential was assessed using Western immunoblotting for manganese superoxide dismutase and copper zinc superoxide dismutase enzymes. Radiotherapy was delivered using a linear accelerator. Cell cycle analysis was performed using flow cytometry. Radiotherapy at 3.5 Gy induced a 5.9-fold increase in apoptosis of DU145 cells. Subapoptotic doses of EGCG (1.5-7.5 μM) significantly reduced ionizing radiation-induced apoptosis (P < .001), with the inhibitory effect of EGCG on ionizing radiation being most effective when added 30 minutes before radiotherapy (P < .001). In addition, when radiotherapy and EGCG were used together, an approximate 1.5-fold increase in manganese superoxide dismutase levels was seen compared with the control and a 2-fold increase compared with radiotherapy alone. Radiotherapy is effective in inducing apoptosis in DU145 cells, but its effect was significantly reduced in the presence of EGCG, and this was associated with an increase in the induction of manganese superoxide dismutase. Copyright © 2011 Elsevier Inc. All rights reserved.

Epigallocatechin gallate as a modulator of Campylobacter resistance to macrolide antibiotics.

PubMed

Kurinčič, Marija; Klančnik, Anja; Smole Možina, Sonja

2012-11-01

Comprehensive therapeutic use of macrolides in humans and animals is important in the selection of macrolide-resistant Campylobacter isolates. This study shows high co-resistance to erythromycin, azithromycin, clarithromycin, dirithromycin and tylosin, with contributions from the 23S rRNA gene and drug efflux systems. The CmeABC efflux pump plays an important role in reduced macrolide susceptibility, accompanied by contributions from the CmeDEF efflux pump and potentially a third efflux pump. To improve clinical performance of licensed antibiotics and chemotherapeutic agents, it is important to understand the factors in Campylobacter that affect susceptibility to macrolide antibiotics. Using mutants that lack the functional genes coding for the CmeB and CmeF efflux pump proteins and the CmeR transcriptional repressor, we show that these efflux pumps are potential targets for the development of therapeutic strategies that use a combination of a macrolide with an efflux pump inhibitor (EPI) to restore macrolide efficacy. The natural phenolic compound epigallocatechin gallate (EGCG) has good modulatory activity over the extrusion across the outer membrane of the macrolides tested, both in sensitive and resistant Campylobacter isolates. Comparing EGCG with known chemical EPIs, correlations in the effects on the particular macrolide antibiotics were seen. EGCG modifies Campylobacter multidrug efflux systems and thus could have an impact on restoring macrolide efficacy in resistant strains. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Epigallocatechin-3-gallate ameliorates intrahepatic cholestasis of pregnancy by inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9.

PubMed

Zhang, Mei; Xu, Meimei

2017-10-01

Matrix metalloproteinase (MMP)-2 and matrix metalloproteinase-9 are involved in many illnesses affecting pregnant women, including intrahepatic cholestasis of pregnancy (ICP), a serious liver abnormality during pregnancy. Epigallocatechin-3-gallate (EGCG) has been widely reported to inhibit activities of MMP-2 and MMP-9. We aimed to investigate the role of EGCG in ameliorating ICP symptoms in a rat model. Using 17α-ethinylestradiol to induce ICP in pregnant rats, we investigated the efficacy of EGCG administration on ICP symptoms, including bile flow rate, total bile acids (TBA) and MMP-2 and MMP-9 activities. Correlation study was conducted among levels of the two MMPs with other ICP symptoms. In ICP rats, activities of both MMP-2 and MMP-9 were significantly elevated. EGCG administration could inhibit the upregulation of MMP-2 and MMP-9 post-transcriptionally. Furthermore, EGCG ameliorated ICP symptoms, as evidenced by restored bile flow rate and TBA, showing efficient treatment outcomes. At last, levels of TBA and the two MMPs were found to be strongly correlated. Our study demonstrates that, for the first time, the efficacy of EGCG in ameliorating ICP symptoms by inhibiting both MMP-2 and MMP-9, which supports its potential as a novel drug in ameliorating ICP. © 2017 Société Française de Pharmacologie et de Thérapeutique.

(-)-Epigallocatechin gallate but not chlorogenic acid upregulates osteoprotegerin synthesis through regulation of bone morphogenetic protein-4 in osteoblasts.

PubMed

Fujita, Kazuhiko; Otsuka, Takanobu; Yamamoto, Naohiro; Kainuma, Shingo; Ohguchi, Reou; Kawabata, Tetsu; Sakai, Go; Kuroyanagi, Gen; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Tokuda, Haruhiko

2017-07-01

Chlorogenic acid (CGA) is a primary phenolic component of coffee and (-)-epigallocatechin gallate (EGCG) is a primary flavonoid component of green tea, both of which have been documented to possess beneficial health properties. A previous study by the present authors demonstrated that p38 mitogen-activated protein kinase (MAPK) may be associated with osteoprotegerin synthesis stimulated by bone morphogenetic protein-4 (BMP-4) in osteoblast-like MC3T3-E1 cells. In the present study, the effects of CGA and EGCG on BMP-4-stimulated osteoprotegerin synthesis in MC3T3-E1 cells were investigated. It was observed that CGA had no effect on osteoprotegerin release stimulated by BMP-4, whereas EGCG significantly enhanced BMP-4-stimulated osteoprotegerin release (P=0.003). Levels of osteoprotegerin mRNA expression induced by BMP-4 were also significantly increased by EGCG (P=0.03). By contrast, EGCG had no significant effect on phosphorylation of Smad1 or p38 MAPK induced by BMP-4. In addition, EGCG had little effect on BMP-induced phosphorylation of p70 S6 kinase; however rapamycin, as an inhibitor of p70 S6 kinase, significantly suppressed osteoprotegerin release (P=0.007). These data suggest that EGCG but not CGA may upregulate the synthesis of osteoprotegerin induced by BMP-4 in osteoblasts.

Preparative separation and purification of epigallocatechin gallate from green tea extracts using a silica adsorbent containing β-cyclodextrin.

PubMed

Lai, Shih-Ming; Gu, Jhe-Yu; Huang, Bing-Hao; Chang, Chieh-Ming J; Lee, Wen-Lung

2012-03-01

A silica adsorbent containing β-cyclodextrin (β-CD) has been developed and used for the separation and purification of epigallocatechin gallate (EGCG) from the green tea extracts. The batch adsorption experiments demonstrated that, the β-CD bonded silica adsorbent possessed excellent adsorption equilibrium capacity (> 55 mg/g adsorbent) and adsorption ratio (>95%) for EGCG compared to the other tea catechins and caffeine. The excellent adsorption capacity and selectivity for EGCG are attributed to the specific interactions between β-CD and EGCG. The preparative separation and purification performance of EGCG on the β-CD bonded silica column (220 mm L × 15 mm i.d., 40-63 μm) was then evaluated. The column was operated in the polar organic mode using methanol/acetonitrile/acetic acid as the mobile phase and eluted under a three-step gradient elution program. The sample was dissolved in acetonitrile and loaded on a preparative scale of about 0.8 mg/g adsorbent. Under the optimal chromatographic conditions, the target compound, EGCG, being the most retained species, was obtained at a purity of about 90% with a recovery of about 90%. The productivity of EGCG was about 6 mg per injection, which can be further increased by scaling-up the chromatographic system. Copyright © 2012 Elsevier B.V. All rights reserved.

In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity

PubMed Central

Li, Sainan; Wu, Liwei; Feng, Jiao; Li, Jingjing; Liu, Tong; Zhang, Rong; Xu, Shizan; Cheng, Keran; Zhou, Yuqing; Zhou, Shunfeng; Kong, Rui; Chen, Kan; Wang, Fan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Dai, Weiqi; Guo, Chuanyong

2016-01-01

Glycolysis, as an altered cancer cell-intrinsic metabolism, is an essential hallmark of cancer. Phosphofructokinase (PFK) is a metabolic sensor in the glycolytic pathway, and restricting the substrate availability for this enzyme has been researched extensively as a target for chemotherapy. In the present study, we investigated that the effects of epigallocatechin-3-gallate (EGCG), an active component of green tea, on inhibiting cell growth and inducing apoptosis by promoting a metabolic shift away from glycolysis in aerobic glycolytic hepatocellular carcinoma (HCC) cells. EGCG modulated the oligomeric structure of PFK, potentially leading to metabolic stress associated apoptosis and suggesting that EGCG acts by directly suppressing PFK activity. A PFK activity inhibitor enhanced the effect, while the allosteric activator reversed EGCG-induced HCC cell death. PFK siRNA knockdown-induced apoptosis was not reversed by the activator. EGCG enhanced the effect of sorafenib on cell growth inhibition in both aerobic glycolytic HCC cells and in a xenograft mouse model. The present study suggests a potential role for EGCG as an adjuvant in cancer therapy, which merits further investigation at the clinical level. PMID:27349173

Epigallocatechin Gallate Has a Neurorescue Effect in a Mouse Model of Parkinson Disease.

PubMed

Xu, Qi; Langley, Monica; Kanthasamy, Anumantha G; Reddy, Manju B

2017-10-01

Background: Parkinson disease (PD) is a neurodegenerative disorder that has been associated with many factors, including oxidative stress, inflammation, and iron accumulation. The antioxidant, anti-inflammatory, and iron-chelating properties of epigallocatechin gallate (EGCG), a major polyphenol in green tea, may offer protection against PD. Objective: We sought to determine the neurorescue effects of EGCG and the role of iron in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Methods: We evaluated the neurorescue effect of EGCG (25 mg/kg, 7 d, oral administration) against MPTP-induced (20 mg/kg, 3 d, intraperitoneal injection) neurodegeneration in C57 male black mice. Thirty mice weighing ∼25 g were divided into 3 groups: control, MPTP, and MPTP + EGCG. The neurorescue effect of EGCG was assessed with the use of motor behavior tests, neurotransmitter analysis, oxidative stress indicators, and iron-related protein expression. Results: Compared with the control group, MPTP treatment shortened the mice's latency to fall from the rotarod by 16% ( P < 0.05), decreased the striatal dopamine concentration by 58% ( P < 0.001) and dihydroxyphenylacetic acid by 35% ( P < 0.05), and increased serum protein carbonyls by 71% ( P = 0.07). However, EGCG rescued MPTP-induced neurotoxicity by increasing the rotational latency by 17% ( P < 0.05) to a value similar to the control group. Striatal dopamine concentrations were 40% higher in the MPTP + EGCG group than in the MPTP group ( P < 0.05), but the values were significantly lower than in the control group. Compared with the MPTP and control groups, mice in the MPTP + EGCG group had higher substantia nigra ferroportin expression (44% and 35%, respectively) ( P < 0.05) but not hepcidin and divalent metal transporter 1 expression. Conclusion: Overall, our study demonstrated that EGCG regulated the iron-export protein ferroportin in substantia nigra, reduced oxidative stress, and exerted a neurorescue effect

Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1β-stimulated human osteoarthritis chondrocytes: potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5.

PubMed

Rasheed, Zafar; Rasheed, Naila; Al-Shaya, Osama

2018-04-01

MicroRNAs (miRNAs) are short, non-coding RNAs involved in almost all cellular processes. Epigallocatechin-3-O-gallate (EGCG) is a green tea polyphenol and is known to exert anti-arthritic effects by inhibiting genes associated with osteoarthritis (OA). This study was undertaken to investigate the global effect of EGCG on interleukin-1β (IL-1β)-induced expression of miRNAs in human chondrocytes. Human chondrocytes were derived from OA cartilage and then treated with EGCG and IL-1β. Human miRNA microarray technology was used to determine the expression profile of 1347 miRNAs. Microarray results were verified by taqman assays and transfection of chondrocytes with miRNA inhibitors. Out of 1347 miRNAs, EGCG up-regulated expression of 19 miRNAs and down-regulated expression of 17 miRNAs, whereas expression of 1311 miRNAs remains unchanged in IL-1β-stimulated human OA chondrocytes. Bioinformatics approach showed that 3`UTR of ADAMTS5 mRNA contains the 'seed-matched-sequence' for hsa-miR-140-3p. IL-1β-induced expression of ADAMTS5 correlated with down-regulation of hsa-miR-140-3p. Importantly, EGCG inhibited IL-1β-induced ADAMTS5 expression and up-regulated the expression of hsa-miR-140-3p. This EGCG-induced co-regulation between ADAMTS5 and hsa-miR-140-3p becomes reversed in OA chondrocytes transfected with anti-miR-140-3p. This study provides an important insight into the molecular basis of the reported anti-arthritic effects of EGCG. Our data indicate that the potential of EGCG in OA chondrocytes may be related to its ability to globally inhibit inflammatory response via modulation of miRNAs expressions.

Epigallocatechin-3-gallate suppressed the over-expression of HSP 70 and MDR1 induced by heat shock in SGC 7901.

PubMed

Tang, Xiao-Yan; Zhu, You-Qing

2008-06-01

This study investigated the effects of epigallocatechin-3-gallate (EGCG) on the expression of HSP 70 and MDR 1. SGC-7901 cells were cultured with RPMI 1640 medium. The single or combined effects of EGCG (0.1, 1, 10, 20, and 40 micromol/L) and heat shock were examined by MTT assay. The expression of HSP 70 and MDR 1 was semi-quantified by the reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry method (SP staining). EGCG suppressed cell proliferation at a time- and dose-dependent manner. The effects of combined treatment with EGCG and heat shock on the growth of SGC-7901 cells were stronger than single effects of EGCG. After using EGCG for 24 h, 48 h and 72 h, the IC50s were 112.5 micromol/l, 21.41 micromol/l and 5.24 micromol/l, respectively. Heat shock stimulated the over-expression of HSP 70, especially after heat shock for 8 h, as well as MDR1 after heat shock for 24 h. But EGCG suppressed the over-expression induced by heat shock. The authors conclude that EGCG inhibited the proliferation of SGC-7901, and EGCG combined with heat shock strengthened the effects. Heat shock weakened the over-expression of HSP 70 and MDR1; however, EGCG suppressed the over-expression of HSP 70 and MDR1 induced by heat shock. EGCG combined with heat shock may enhance the sensitivity of drugs to tumors.

(−)-Epigallocatechin gallate but not chlorogenic acid upregulates osteoprotegerin synthesis through regulation of bone morphogenetic protein-4 in osteoblasts

PubMed Central

Fujita, Kazuhiko; Otsuka, Takanobu; Yamamoto, Naohiro; Kainuma, Shingo; Ohguchi, Reou; Kawabata, Tetsu; Sakai, Go; Kuroyanagi, Gen; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Tokuda, Haruhiko

2017-01-01

Chlorogenic acid (CGA) is a primary phenolic component of coffee and (−)-epigallocatechin gallate (EGCG) is a primary flavonoid component of green tea, both of which have been documented to possess beneficial health properties. A previous study by the present authors demonstrated that p38 mitogen-activated protein kinase (MAPK) may be associated with osteoprotegerin synthesis stimulated by bone morphogenetic protein-4 (BMP-4) in osteoblast-like MC3T3-E1 cells. In the present study, the effects of CGA and EGCG on BMP-4-stimulated osteoprotegerin synthesis in MC3T3-E1 cells were investigated. It was observed that CGA had no effect on osteoprotegerin release stimulated by BMP-4, whereas EGCG significantly enhanced BMP-4-stimulated osteoprotegerin release (P=0.003). Levels of osteoprotegerin mRNA expression induced by BMP-4 were also significantly increased by EGCG (P=0.03). By contrast, EGCG had no significant effect on phosphorylation of Smad1 or p38 MAPK induced by BMP-4. In addition, EGCG had little effect on BMP-induced phosphorylation of p70 S6 kinase; however rapamycin, as an inhibitor of p70 S6 kinase, significantly suppressed osteoprotegerin release (P=0.007). These data suggest that EGCG but not CGA may upregulate the synthesis of osteoprotegerin induced by BMP-4 in osteoblasts. PMID:28672948

Epigallocatechin-3-gallate attenuates lipopolysaccharide-induced mastitis in rats via suppressing MAPK mediated inflammatory responses and oxidative stress.

PubMed

Chen, Jinglou; Xu, Jun; Li, Jingjing; Du, Lifen; Chen, Tao; Liu, Ping; Peng, Sisi; Wang, Mingwei; Song, Hongping

2015-05-01

Green tea (Camellia sinensis) is an extremely popular beverage worldwide. Epigallocatechin-3-gallate (EGCG) is one of the major catechins isolated from green tea and contributes to its beneficial therapeutic functions including antioxidant, anti-inflammatory and anti-cancer effects. However, the effect of EGCG on mastitis is not yet known. This study was to investigate the protective potential of EGCG against mastitis in rats. The rat mastitis model was induced by injecting lipopolysaccharide (LPS) into the duct of mammary gland. The mammary gland was collected after the experimental period. The levels of mammary oxidative stress and inflammatory responses were assessed by measuring the local activities of antioxidant enzymes and the levels of inflammatory cytokines. The mammary expressions of mitogen-activated protein kinases (MAPKs), nuclear factor κB-p65 (NFκB-p65) and hypoxia-inducible factor-1α (HIF-1α) were evaluated by western blot analysis. It was found that EGCG obviously normalized LPS-induced low activities of antioxidant enzymes as well as decreased the high levels of inflammatory cytokines. Additionally, EGCG inhibited the mammary over-expression of MAPKs, NFκB-p65 and HIF-1α. These results indicated that EGCG was able to attenuate LPS-induced mastitis in rats by suppressing MAPK related oxidative stress and inflammatory responses. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition of interaction between epigallocatechin-3-gallate and myofibrillar protein by cyclodextrin derivatives improves gel quality under oxidative stress.

PubMed

Zhang, Yumeng; Chen, Lin; Lv, Yuanqi; Wang, Shuangxi; Suo, Zhiyao; Cheng, Xingguang; Xu, Xinglian; Zhou, Guanghong; Li, Zhixi; Feng, Xianchao

2018-06-01

High levels of polyphenols can interact with myofibrillar proteins (MPs), causing damage to a MP emulsion gel. In this study, β-cyclodextrins were used to reduce covalent and non-covalent interaction between epigallocatechin-3-gallate (EGCG) and MPs under oxidative stress. The loss of both thiol and free amine groups and the unfolding of MPs caused by EGCG (80 μM/g protein) were significantly prevented by β-cyclodextrins, and the structural stability and solubility were improved. MP emulsion gel treated with EGCG (80 μM/g protein) had the highest cooking loss (68.64%) and gel strength (0.51 N). Addition of β-cyclodextrins significantly reduced cooking loss (26.24-58.20%) and improved gel strength (0.31-0.41 N) of MP emulsion gel jeopardized by EGCG under oxidative stress. Damage to the emulsifying properties of MPs caused by EGCG was significantly prevented by addition of β-cyclodextrins. β-cyclodextrins reduced interaction between EGCG and MPs in the order Methyl-β-cyclodextrin > (2-Hydroxypropyl)-β-cyclodextrin > β-cyclodextrin. In absence of EGCG, addition of β-cyclodextrins partly protected MPs from oxidative attack and improved its solubility. It is concluded that β-cyclodextrins does not markedly reduce the antioxidant ability of EGCG according to carbonyl analysis, and can effectively increase EGCG loading to potentially provide more durable antioxidant effect for meat products during processing, transportation and storage. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Protective Effects of Epigallocatechin Gallate Against Distant Organ Damage After Severe Skin Burns--Experimental Study Using a Rat Model of Thermal Trauma.

PubMed

Hosnuter, Mubin; Melikoglu, Cenk; Aslan, Cem; Saglam, Gulcan; Sutcu, Recep

2015-01-01

Epigallocatechin gallate (EGCG), a green tea polyphenol, has potent antioxidant properties. The purpose of the present study was to examine the possible preventative effects of EGCG against internal organ injury due to large-surface skin burns in a rat model. The study design involved three groups of rats: a sham group and two groups with 25-30% full-thickness burns: (a) the sham group without burns or treatment (n=18); (b) the control burn group (burns+sterile saline, n=18); and (c) the burn treatment group (burns+treatment with EGCG, n=18). EGCG was administered intraperitoneally immediately after the thermal injury, and daily in 100 μmol/kg doses. Kidney and lung tissue samples were taken to determine the levels of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and glutathione peroxidase (GPX) after the first, third and seventh post-burn days. In the EGCG-treated burn group, SOD and GPX activity were significantly higher than in the burn control group. Additionally, MDA and TNF-α levels were significantly lower in the EGCG-treated burn group. Based on this study, it might be anticipated that EGCG treatment may be beneficial in burn injury cases.

Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation.

PubMed

Klaus, S; Pültz, S; Thöne-Reineke, C; Wolfram, S

2005-06-01

To examine the antiobesity effect of epigallocatechin gallate (EGCG), a green tea bioactive polyphenol in a mouse model of diet-induced obesity. Obesity was induced in male New Zealand black mice by feeding of a high-fat diet. EGCG purified from green tea (TEAVIGO) was supplemented in the diet (0.5 and 1%). Body composition (quantitative magnetic resonance), food intake, and food digestibility were recorded over a 4-week period. Animals were killed and mRNA levels of uncoupling proteins (UCP1-3), leptin, malic enzyme (ME), stearoyl-CoA desaturase-1 (SCD1), glucokinase (GK), and pyruvate kinase (PK) were analysed in different tissues. Also investigated were acute effects of orally administered EGCG (500 mg/kg) on body temperature, activity (transponders), and energy expenditure (indirect calorimetry). Dietary supplementation of EGCG resulted in a dose-dependent attenuation of body fat accumulation. Food intake was not affected but faeces energy content was slightly increased by EGCG, indicating a reduced food digestibility and thus reduced long-term energy absorption. Leptin and SCD1 gene expression in white fat was reduced but SCD1 and UCP1 expression in brown fat was not changed. In liver, gene expression of SCD1, ME, and GK was reduced and that of UCP2 increased. Acute oral administration of EGCG over 3 days had no effect on body temperature, activity, and energy expenditure, whereas respiratory quotient during night (activity phase) was decreased, supportive of a decreased lipogenesis and increased fat oxidation. Dietary EGCG attenuated diet-induced body fat accretion in mice. EGCG apparently promoted fat oxidation, but its fat-reducing effect could be entirely explained by its effect in reducing diet digestibility.

Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome.

PubMed

Catuara-Solarz, Silvina; Espinosa-Carrasco, Jose; Erb, Ionas; Langohr, Klaus; Gonzalez, Juan Ramon; Notredame, Cedric; Dierssen, Mara

2016-01-01

Intellectual disability in Down syndrome (DS) is accompanied by altered neuro-architecture, deficient synaptic plasticity, and excitation-inhibition imbalance in critical brain regions for learning and memory. Recently, we have demonstrated beneficial effects of a combined treatment with green tea extract containing (-)-epigallocatechin-3-gallate (EGCG) and cognitive stimulation in young adult DS individuals. Although we could reproduce the cognitive-enhancing effects in mouse models, the underlying mechanisms of these beneficial effects are unknown. Here, we explored the effects of a combined therapy with environmental enrichment (EE) and EGCG in the Ts65Dn mouse model of DS at young age. Our results show that combined EE-EGCG treatment improved corticohippocampal-dependent learning and memory. Cognitive improvements were accompanied by a rescue of cornu ammonis 1 (CA1) dendritic spine density and a normalization of the proportion of excitatory and inhibitory synaptic markers in CA1 and dentate gyrus.

Combined Treatment With Environmental Enrichment and (-)-Epigallocatechin-3-Gallate Ameliorates Learning Deficits and Hippocampal Alterations in a Mouse Model of Down Syndrome

PubMed Central

Gonzalez, Juan Ramon; Notredame, Cedric

2016-01-01

Intellectual disability in Down syndrome (DS) is accompanied by altered neuro-architecture, deficient synaptic plasticity, and excitation-inhibition imbalance in critical brain regions for learning and memory. Recently, we have demonstrated beneficial effects of a combined treatment with green tea extract containing (-)-epigallocatechin-3-gallate (EGCG) and cognitive stimulation in young adult DS individuals. Although we could reproduce the cognitive-enhancing effects in mouse models, the underlying mechanisms of these beneficial effects are unknown. Here, we explored the effects of a combined therapy with environmental enrichment (EE) and EGCG in the Ts65Dn mouse model of DS at young age. Our results show that combined EE-EGCG treatment improved corticohippocampal-dependent learning and memory. Cognitive improvements were accompanied by a rescue of cornu ammonis 1 (CA1) dendritic spine density and a normalization of the proportion of excitatory and inhibitory synaptic markers in CA1 and dentate gyrus. PMID:27844057

Competitive binding of (-)-epigallocatechin-3-gallate and 5-fluorouracil to human serum albumin: A fluorescence and circular dichroism study

NASA Astrophysics Data System (ADS)

Yuan, Lixia; Liu, Min; Liu, Guiqin; Li, Dacheng; Wang, Zhengping; Wang, Bingquan; Han, Jun; Zhang, Min

2017-02-01

Combination therapy with more than one therapeutic agent can improve therapeutic efficiency and decrease drug resistance. In this study, the interactions of human serum albumin (HSA) with individual or combined anticancer drugs, (-)-epigallocatechin-3-gallate (EGCG) and 5-fluorouracil (FU), were investigated by fluorescence and circular dichroism (CD) spectroscopy. The results demonstrated that the interaction of EGCG or FU with HSA is a process of static quenching and EGCG formed a more stable complex. The competitive experiments of site markers suggested that both anti-carcinogens mainly bound to site I (subdomain IIA). The interaction forces which play important roles in the binding process were discussed based on enthalpy and entropy changes. Moreover, the competition binding model for a ternary system was proposed so as to precisely calculate the binding parameters. The results demonstrated that one drug decreased the binding affinity of another drug with HSA, resulting in the increasing free drug concentration at the action sites. CD studies indicated that there was an alteration in HSA secondary structure due to the binding of EGCG and FU. It can be concluded that the combination of EGCG with FU may enhance anticancer efficacy. This finding may provide a theoretical basis for clinical treatments.

Epigallocatechin-3-gallate (EGCG) and green tea polyphenols do not improve stallion semen parameters during cooling at 4°C.

PubMed

Bucci, D; Spinaci, M; Mislei, B; Gadani, B; Rizzato, G; Love, C C; Tamanini, C; Galeati, G; Mari, G

2017-04-01

Stallion semen storage for artificial insemination is mainly based on liquid cooled storage. In many stallions this technique maintains sperm quality for an extended period of time (24-72 hr) at 7°C. While this technique is commonly used in the horse industry, there can be a decline in fertility in some stallions, due to an inability of their sperm to tolerate the cool storage process. The aim of the present work was to evaluate the effect of two natural antioxidants (epigallocatechin-3-gallate (EGCG) at 20, 60 and 120 μm and green tea polyphenols, and p at .001, .01 and .1 mg/ml) on some sperm parameters (sperm motility, viability/acrosome integrity and DNA quality) in extended semen immediately after its collection (T0) and after 2, 6, 24 and 48 hr of cool storage. Two ejaculates from three trotter stallions were analysed after 48 hr of storage at 4°C. No beneficial effect on the analysed parameters was observed: the two antioxidants were not able to improve sperm quality after 48 hr of storage. These results are in agreement with previous findings on the effect of different antioxidants reported by other researches, who have demonstrated that stallion semen keeps good antioxidant capacity after dilution for 24 hr. In conclusion, the positive effect exerted by antioxidant molecules in other species is not confirmed in the equine one. © 2017 Blackwell Verlag GmbH.

The Heat Shock Protein 90 Inhibitor, Epigallocatechin Gallate, has Anti-Cancer Activity in a Novel Human Prostate Cancer Progression Model

PubMed Central

Moses, Michael A.; Henry, Ellen C.; Ricke, William A.; Gasiewicz, Thomas A.

2015-01-01

(−)-Epigallocatechin gallate (EGCG), a major tea polyphenol, elicits anti-cancer effects. However, the mechanism of action is not fully understood. Our laboratory previously showed that EGCG inhibits heat shock protein 90 (HSP90). We utilized non-tumorigenic (NT), tumorigenic, and metastatic cancer cells from a novel human prostate cancer (PRCA) progression model to test the hypotheses that certain stages are more or less sensitive to EGCG and that sensitivity is related to HSP90 inhibition. Treatment of cells with EGCG, novobiocin (NB), or 17-AAG resulted in more potent cytotoxic effects on tumorigenic and metastatic cells than NT cells. When tumorigenic or metastatic cells were grown in vivo, mice supplemented with 0.06% EGCG in drinking water developed significantly smaller tumors than untreated mice. Furthermore, EGCG prevented malignant transformation in vivo using the full PRCA model. To elucidate the mechanism of EGCG action, we performed binding assays with EGCG-Sepharose, a C-terminal HSP90 antibody, and HSP90 mutants. These experiments revealed that EGCG-Sepharose bound more HSP90 from metastatic cells compared to NT cells and binding occurred through the HSP90 C-terminus. Additionally, EGCG bound HSP90 mutants that mimic both complexed and uncomplexed HSP90. Consistent with HSP90 inhibitory activity, EGCG, NB, and 17-AAG induced changes in HSP90-client proteins in NT cells and larger differences in metastatic cells. These data suggest that EGCG may be efficacious for the treatment of PRCA because it preferentially targets cancer cells and inhibits a molecular chaperone supportive of the malignant phenotype. PMID:25604133

Epigallocatechin-3-Gallate Suppresses Human Herpesvirus 8 Replication and Induces ROS Leading to Apoptosis and Autophagy in Primary Effusion Lymphoma Cells

PubMed Central

Tsai, Ching-Yi; Chen, Chang-Yu; Chiou, Yee-Hsuan; Shyu, Huey-Wen; Lin, Kuan-Hua; Chou, Miao-Chen; Huang, Mei-Han; Wang, Yi-Fen

2017-01-01

Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to induce cell death in cancer cells. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpesvirus 8 (HHV8). In this study, we examined the role of EGCG on PEL cells in cell death and HHV8 replication. We performed trypan blue exclusion assay to assess the cell viability of PEL cells, flow cytometry analysis to examine the cell cycle distribution and reactive oxygen species (ROS) generation, caspase-3 activity to assay apoptosis, acridine orange staining to determine autophagy, and immunoblotting to detect the protein levels involved in apoptosis and autophagy as well as mitogen activated protein kinases (MAPKs) activation upon EGCG treatment. The expression of the HHV8 lytic gene was determined by luciferase reporter assay and reverse transcription-PCR, and viral progeny production was determined by PCR. Results revealed that EGCG induced cell death and ROS generation in PEL cells in a dose-dependent manner. N-acetylcysteine (NAC) inhibited the EGCG-induced ROS and rescued the cell from EGCG-induced cell death. Even though EGCG induced ROS generation in PEL cells, it reduced the production of progeny virus from PEL cells without causing HHV8 reactivation. These results suggest that EGCG may represent a novel strategy for the treatment of HHV8 infection and HHV8-associated lymphomas. PMID:29267216

Adsorption characteristics of (-)-epigallocatechin gallate and caffeine in the extract of waste tea on macroporous adsorption resins functionalized with chloromethyl, amino, and phenylamino groups.

PubMed

Liu, Yongfeng; Bai, Qingqing; Lou, Song; Di, Duolong; Li, Jintian; Guo, Mei

2012-02-15

According to the Friedel-Crafts and amination reaction, a series of macroporous adsorption resins (MARs) with novel structures were synthesized and identified by the Brunauer-Emmett-Teller (BET) method and Fourier transform infrared (FTIR) spectra, and corresponding adsorption behaviors for (-)-epigallocatechin gallate (EGCG) and caffeine (CAF) extracted from waste tea were systemically investigated. Based on evaluation of adsorption kinetics, the kinetic data were well fitted by pseudo-second-order kinetics. Langmuir, Freundlich, Temkin-Pyzhev, and Dubinin-Radushkevich isotherms were selected to illustrate the adsorption process of EGCG and CAF on the MARs. Thermodynamic parameters were adopted to explain in-depth information of inherent energetic changes associated with the adsorption process. The effect of temperature on EGCG and CAF adsorption by D101-3 was further expounded. Van der Waals force, hydrogen bonding, and electrostatic interaction were the main driving forces for the adsorption of EGCG and CAF on the MARs. This study might provide a scientific reference point to aid the industrial large-scale separation and enrichment of EGCG from the extracts of waste tea using modified MARs.

Epigallocatechin-3-gallate and penta-O-galloyl-β-D-glucose inhibit protein phosphatase-1.

PubMed

Kiss, Andrea; Bécsi, Bálint; Kolozsvári, Bernadett; Komáromi, István; Kövér, Katalin E; Erdődi, Ferenc

2013-01-01

Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) are responsible for the dephosphorylation of the majority of phosphoserine/threonine residues in cells. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG) and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), polyphenolic constituents of green tea and tannins, inhibit the activity of the PP1 recombinant δ-isoform of the PP1 catalytic subunit and the native PP1 catalytic subunit (PP1c) with IC(50) values of 0.47-1.35 μm and 0.26-0.4 μm, respectively. EGCG and PGG inhibit PP2Ac less potently, with IC(50) values of 15 and 6.6 μm, respectively. The structure-inhibitory potency relationships of catechin derivatives suggests that the galloyl group may play a major role in phosphatase inhibition. The interaction of EGCG and PGG with PP1c was characterized by NMR and surface plasmon resonance-based binding techniques. Competitive binding assays and molecular modeling suggest that EGCG docks at the hydrophobic groove close to the catalytic center of PP1c, partially overlapping with the binding surface of microcystin-LR or okadaic acid. This hydrophobic interaction is further stabilized by hydrogen bonding via hydroxyl/oxo groups of EGCG to PP1c residues. Comparative docking shows that EGCG binds to PP2Ac in a similar manner, but in a distinct pose. Long-term treatment (24 h) with these compounds and other catechins suppresses the viability of HeLa cells with a relative effectiveness reminiscent of their in vitro PP1c-inhibitory potencies. The above data imply that the phosphatase-inhibitory features of these polyphenols may be implicated in the wide spectrum of their physiological influence. © 2012 The Authors Journal compilation © 2012 FEBS.

Epigallocatechin gallate induces a hepatospecific decrease in the CYP3A expression level by altering intestinal flora.

PubMed

Ikarashi, Nobutomo; Ogawa, Sosuke; Hirobe, Ryuta; Kon, Risako; Kusunoki, Yoshiki; Yamashita, Marin; Mizukami, Nanaho; Kaneko, Miho; Wakui, Nobuyuki; Machida, Yoshiaki; Sugiyama, Kiyoshi

2017-03-30

In previous studies, we showed that a high-dose intake of green tea polyphenol (GP) induced a hepatospecific decrease in the expression and activity of the drug-metabolizing enzyme cytochrome P450 3A (CYP3A). In this study, we examined whether this decrease in CYP3A expression is induced by epigallocatechin gallate (EGCG), which is the main component of GP. After a diet containing 1.5% EGCG was given to mice, the hepatic CYP3A expression was measured. The level of intestinal bacteria of Clostridium spp., the concentration of lithocholic acid (LCA) in the feces, and the level of the translocation of pregnane X receptor (PXR) to the nucleus in the liver were examined. A decrease in the CYP3A expression level was observed beginning on the second day of the treatment with EGCG. The level of translocation of PXR to the nucleus was significantly lower in the EGCG group. The fecal level of LCA was clearly decreased by the EGCG treatment. The level of intestinal bacteria of Clostridium spp. was also decreased by the EGCG treatment. It is clear that the hepatospecific decrease in the CYP3A expression level observed after a high-dose intake of GP was caused by EGCG. Because EGCG, which is not absorbed from the intestine, causes a decrease in the level of LCA-producing bacteria in the colon, the level of LCA in the liver decreases, resulting in a decrease in the nuclear translocation of PXR, which in turn leads to the observed decrease in the expression level of CYP3A. Copyright © 2017 Elsevier B.V. All rights reserved.

New Drugs for Prevention of Breast Cancer Metastases

DTIC Science & Technology

1999-07-01

the principal anticancer catechin, epigallocatechin gallate ( EGCg ). A 3-way mixture of epicatechin (EC), EGCg and glaucarubolone was more effective...DAPI, 4’,6-diamidino-2-phenylindole; DMSO, dimethyl sulfoxide; EGF, epidermal growth factor; EGCg , epigallocatechin gallate . ABSTRACT A drug...preferentially in HeLa and human and mouse mammary adenocarcinoma by the naturally-occurring catechin of green tea, epigallocatechin gallate ( EGCg ). With

Effect of topical epigallocatechin gallate on corneal neovascularization in rabbits.

PubMed

Koh, Chang Hyun; Lee, Hyun Soo; Chung, Sung Kun

2014-05-01

The aim of this study was to evaluate the efficacy of topical application of epigallocatechin gallate (EGCG) for the treatment of corneal neovascularization in a rabbit model. Corneal neovascularization was induced in 12 rabbits by placing a black silk suture in the corneal stroma (24 eyes) for a week. After suturing, 1 randomly chosen eye of the 12 rabbits was treated with topical EGCG at 2 different concentrations: 0.01% (group 1) and 0.1% (group 2), whereas the contralateral eyes were treated with sterilized balanced salt solution as the control. All eye drops were applied for 2 weeks after suturing. The suture materials were removed from all eyes on day 7. The surface area of corneal neovascularization was measured and analyzed in all eyes on days 7 and 14. On day 14, all eyes were extracted to measure the concentrations of vascular endothelial growth factor (VEGF) messenger RNA and cyclooxygenase-2 (COX-2) protein. The surface area of induced corneal neovascularization was significantly smaller only in group 2 compared with that of the control group on days 7 and 14 (P < 0.001). The change in surface area of corneal neovascularization after removal of the suture material was not significantly different between all 3 groups. VEGF messenger RNA levels were significantly lower in group 2 than in the control group (P < 0.001). The concentration of COX-2 was significantly lower in group 2 than in the control group (P = 0.043), but no significant difference was observed between group 1 and the control group. Topical administration of EGCG effectively inhibits corneal neovascularization in rabbits. This inhibitory effect is probably related to the suppression of VEGF and COX-2 meditated angiogenesis.

Anti-skin-aging effect of epigallocatechin gallate by regulating epidermal growth factor receptor pathway on aging mouse model induced by d-Galactose.

PubMed

Chen, Jiming; Li, Yifan; Zhu, Qiangqiang; Li, Tong; Lu, Hao; Wei, Nan; Huang, Yewei; Shi, Ruoyu; Ma, Xiao; Wang, Xuanjun; Sheng, Jun

2017-06-01

Epigallocatechin gallate(EGCG) is a monomer separated from tea catechins, as an well-known antioxidant, which helps fight wrinkles and rejuvenate skin cells. In this study, we investigated the anti-aging effect of EGCG, and to clarify underlying mechanism of skin aging in a d-galactose-induced aging mouse model. Forty-five male mice were divided into 5 groups and treated with different dose of EGCG, Vitamin C (VitC) to mice as a positive control. All groups except vehicle were established aging model induced by d-galactose (200mg/kg/day) that was subcutaneously injected to mice for 8 weeks. Two weeks after injection of d-galactose, EGCG and Vit C groups were simultaneously administered once a day by subcutaneously inject after 5h for injecting d-galactose. The results show that EGCG can be absorbed by the skin. Overall, the conditions of the skin of EGCG-treatment groups were improved, the whole structure of skin were better than control groups, and the levels of oxidative stress and the expression of relate with EGFR proteins were significantly higher than control group after EGCG treatment. All these findings suggest that EGCG can resist skin senility effectively. And the EGFR with relate of downstream proteins are implicated in the skin aging. Copyright © 2017. Published by Elsevier B.V.

Molecular Effects of 13C/DIM in Prostate Cancer

DTIC Science & Technology

2006-04-01

contains several cat- echins including epicatechin, epigallocatechin , epicatechin-3- gallate , and epigallocatechin -3- gallate ( EGCG ). However, EGCG has...indole-3-carbinol (I3C), curcumin, ()-epigallo- catechin-3- gallate ( EGCG ), resveratrol, etc.] have been recognized as cancer chemopreventive agents...Ther 2003; 2:95–103. 15. Chisholm K, Bray BJ, Rosengren RJ. Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB-231 human

Epigallocatechin-3-gallate inhibits IL-6 synthesis and suppresses transsignaling by enhancing soluble gp130 production

PubMed Central

Ahmed, Salahuddin; Marotte, Hubert; Kwan, Kevin; Ruth, Jeffrey H.; Campbell, Phillip L.; Rabquer, Bradley J.; Pakozdi, Angela; Koch, Alisa E.

2008-01-01

Regulation of IL-6 transsignaling by the administration of soluble gp130 (sgp130) receptor to capture the IL-6/soluble IL-6R complex has shown promise for the treatment of rheumatoid arthritis (RA). However, enhancing endogenous sgp130 via alternative splicing of the gp130 gene has not yet been tested. We found that epigallocatechin-3-gallate (EGCG), an anti-inflammatory compound found in green tea, inhibits IL-1β–induced IL-6 production and transsignaling in RA synovial fibroblasts by inducing alternative splicing of gp130 mRNA, resulting in enhanced sgp130 production. Results from in vivo studies using a rat adjuvant-induced arthritis model showed specific inhibition of IL-6 levels in the serum and joints of EGCG-treated rats by 28% and 40%, respectively, with concomitant amelioration of rat adjuvant-induced arthritis. We also observed a marked decrease in membrane-bound gp130 protein expression in the joint homogenates of the EGCG-treated group. In contrast, quantitative RT-PCR showed that the gp130/IL-6Rα mRNA ratio increased by ∼2-fold, suggesting a possible mechanism of sgp130 activation by EGCG. Gelatin zymography results showed EGCG inhibits IL-6/soluble IL-6R–induced matrix metalloproteinase-2 activity in RA synovial fibroblasts and in joint homogenates, possibly via up-regulation of sgp130 synthesis. The results of these studies provide previously undescribed evidence of IL-6 synthesis and transsignaling inhibition by EGCG with a unique mechanism of sgp130 up-regulation, and thus hold promise as a potential therapeutic agent for RA. PMID:18796608

Green tea polyphenol epigallocatechin-3-gallate increases atherosclerotic plaque stability in apolipoprotein E-deficient mice fed a high-fat diet.

PubMed

Wang, Qiming; Zhang, Jian; Li, Yafei; Shi, Haojie; Wang, Hao; Chen, Bingrui; Wang, Fang; Wang, Zemu; Yang, Zhijian; Wang, Liansheng

2018-06-04

Epigallocatechin-3-gallate (EGCG), which is the principal component of green tea, has been shown to prevent the formation of atherosclerosis. However, the effect of EGCG on atherosclerotic plaque stability remains unknown. This study aimed to assess whether EGCG can enhance atherosclerotic plaque stability and to investigate the underlying mechanisms. Apolipoprotein E-deficient mice fed a high-fat diet were injected intraperitoneally with EGCG (10 mg/kg ) for 16 weeks. Cross sections of the brachiocephalic arteries were stained with hematoxylin and eosin (HE) for morphometric analyses or Masson's trichrome for collagen content analyses. Immunohistochemistry was performed to evaluate the percentage of macrophages and smooth muscle cells (SMCs). Protein expression and matrix metalloproteinase (MMP) activity were assayed by Western blot and gelatin zymography, respectively. Serum inflammatory cytokine levels were quantified by enzyme-linked immunosorbent assay. After 16 weeks of feeding the high-fat diet, there was clear atherosclerosis formation in the proximal brachiocephalic artery segments according to HE staining. EGCG treatment significantly increased the thickness of the fibrous cap. In the atherosclerotic plaques of the EGCG group, the relative macrophage content was decreased, whereas the relative SMC and collagen contents were increased. The expression levels of MMP-2, MMP-9 and extracellular matrix metalloproteinase inducer (EMMPRIN) were significantly decreased by EGCG treatment. In addition, EGCG treatment decreased the circulating TNF-a, IL-6, MCP-1 and IFN-γ levels in apolipoprotein E-deficient mice. EGCG promotes atherosclerotic lesion stability in apolipoprotein E-deficient mice. Potentially, these effects are mediated through the inhibition of inflammatory cytokine, MMPs and EMMPRIN expression.

In vitro electrocardiographic and cardiac ion channel effects of (-)-epigallocatechin-3-gallate, the main catechin of green tea.

PubMed

Kang, Jiesheng; Cheng, Hsien; Ji, Junzhi; Incardona, Josephine; Rampe, David

2010-08-01

Epigallocatechin-3-gallate (EGCG) is the major catechin found in green tea. EGCG is also available for consumption in the form of concentrated over-the-counter nutritional supplements. This compound is currently undergoing clinical trials for the treatment of a number of diseases including multiple sclerosis, and a variety of cancers. To date, few data exist regarding the effects of EGCG on the electrophysiology of the heart. Therefore, we examined the effects of EGCG on the electrocardiogram recorded from Langendorff-perfused guinea pig hearts and on cardiac ion channels using patch-clamp electrophysiology. EGCG had no significant effects on the electrocardiogram at concentrations of 3 and 10 microM. At 30 microM, EGCG prolonged PR and QRS intervals, slightly shortened the QT interval, and altered the shape of the ST-T-wave segment. The ST segment merged with the upstroke of the T wave, and we noted a prolongation in the time from the peak of the T wave until the end. Patch-clamp studies identified the KvLQT1/minK K(+) channel as a target for EGCG (IC(50) = 30.1 microM). In addition, EGCG inhibited the cloned human cardiac Na(+) channel Na(v)1.5 in a voltage-dependent fashion. The L-type Ca(2+) channel was inhibited by 20.8% at 30 microM, whereas the human ether-a-go-go-related gene and Kv4.3 cardiac K(+) channels were less sensitive to inhibition by EGCG. ECGC has a number of electrophysiological effects in the heart, and these effects may have clinical significance when multigram doses of this compound are used in human clinical trials or through self-ingestion of large amounts of over-the-counter products enriched in EGCG.

Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties.

PubMed

Azam, S; Hadi, N; Khan, N U; Hadi, S M

2004-10-01

It is believed that anticancer and apoptosis inducing properties of green tea are mediated by it's polyphenolic constituents particularly catechins. A number of reports have shown that green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) is among the most effective chemopreventive and apoptosis-inducing agents present in the beverage. Plant polyphenols are naturally occurring antioxidants but they also exhibit prooxidant properties. Over the last several years we have shown that various classes of plant polyphenols including flavonoids, curcuminoids and tannins are capable of catalyzing oxidative DNA cleavage particularly in the presence of transition metal ions such as copper and iron. With a view to understand the chemical basis of various pharmacological properties of green tea, in this paper we have compared the prooxidant properties of green tea polyphenols--EGCG and EC ((-)-epicatechin). The rate of oxidative DNA degradation as well as hydroxyl radical and superoxide anion formation was found to be greater in the case of EGCG as compared with EC. It was also shown that copper mediated oxidation of EC and EGCG possibly leads to the formation of polymerized polyphenols. Further, it was indicated that copper oxidized catechins were more efficient prooxidants as compared with their unoxidized forms. These results correlate with the observation by others that EGCG is the most effective apoptosis inducing polyphenol present in green tea. They are also in support of our hypothesis that prooxidant action of plant polyphenols may be an important mechanism of their anticancer properties. A model for binding of Cu(II) to EC has been presented where the formation of quinone and a quinone methide has been proposed.

Epigallocatechin gallate protects dopaminergic neurons against 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity by inhibiting microglial cell activation.

PubMed

Li, Rui; Peng, Ning; Du, Fang; Li, Xu-ping; Le, Wei-dong

2006-04-01

To observe whether the dopaminergic neuroprotective effect of (-)-epigallocatechin gallate (EGCG) is associated with its inhibition of microglial cell activation in vivo. The effects of EGCG at different doses on dopaminergic neuronal survival were tested in a methyl-4-phenyl-pyridinium (MPP+)-induced dopaminergic neuronal injury model in the primary mesencephalic cell cultures. With unbiased stereological method, tyrosine hydroxylase-immunoreactive (TH-ir) cells were counted in the A8, A9 and A10 regions of the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57BL/6 mice. The effect of EGCG on microglial activation in the SN was also investigated. Pretreatment with EGCG (1 to 100 micromol/L) significantly attenuated MPP+-induced TH-ir cell loss by 22.2% to 80.5% in the mesencephalic cell cultures. In MPTP-treated C57BL/6 mice, EGCG at a low concentration (1 mg/kg) provided significant protection against MPTP-induced TH-ir cell loss by 50.9% in the whole nigral area and by 71.7% in the A9 region. EGCG at 5 mg/kg showed more prominent protective effect than at 1 or 10 mg/kg. EGCG pretreatment significantly inhibited microglial activation and CD11b expression induced by MPTP. EGCG exerts potent dopaminergic neuroprotective activity by means of microglial inhibition, which shed light on the potential use of EGCG in treatment of Parkinson's disease.

Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines.

PubMed

Ahmed, Reda Saber Ibrahim; Liu, Gang; Renzetti, Andrea; Farshi, Pershang; Yang, Huanjie; Soave, Claire; Saed, Ghassan; El-Ghoneimy, Ashraf Ahmed; El-Banna, Hossny Awad; Foldes, Robert; Chan, Tak-Hang; Dou, Q Ping

2016-10-01

Uterine fibroids (leiomyomas) are very common benign tumors grown on the smooth muscle layer of the uterus, present in up to 75% of reproductive-age women and causing significant morbidity in a subset of this population. Although the etiology and biology of uterine fibroids are unclear, strong evidence supports that cell proliferation, angiogenesis and fibrosis are involved in their formation and growth. Currently the only cure for uterine fibroids is hysterectomy; the available alternative therapies have limitations. Thus, there is an urgent need for developing a novel strategy for treating this condition. The green tea polyphenol epigallocatechin gallate (EGCG) inhibits the growth of uterine leiomyoma cells in vitro and in vivo, and the use of a green tea extract (containing 45% EGCG) has demonstrated clinical activity without side effects in women with symptomatic uterine fibroids. However, EGCG has a number of shortcomings, including low stability, poor bioavailability, and high metabolic transformations under physiological conditions, presenting challenges for its development as a therapeutic agent. We developed a prodrug of EGCG (Pro-EGCG or 1) which shows increased stability, bioavailability and biological activity in vivo as compared to EGCG. We also synthesized prodrugs of EGCG analogs, compounds 2a and 4a, in order to potentially reduce their susceptibility to methylation/inhibition by catechol-O-methyltransferase. Here, we determined the effect of EGCG, Pro-EGCG, and 2a and 4a on cultured human uterine leiomyoma cells, and found that 2a and 4a have potent antiproliferative, antiangiogenic, and antifibrotic activities. J. Cell. Biochem. 117: 2357-2369, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Simultaneous separation and purification of (-)-epigallocatechin gallate and caffeine from tea extract by size exclusion effect on modified porous adsorption material.

PubMed

Zhang, Xiaofeng; Xu, Yi; Zhang, Qing; Cao, Kun; Mu, Xiuni

2016-09-15

A dual-task method for the simultaneous separation and purification of (-)-epigallocatechin gallate (EGCG) and caffeine (CAF) from crude extract of green tea was established by size exclusion effect onto hydroquinone modified porous adsorbents. The results showed that hydroquinone modified porous adsorbents P4 provided the best separation power due to it has more porous structure and phenolic hydroxyl group. The adsorption-desorption behaviors of EGCG and CAF onto P4 adsorbents were investigated. Adsorption kinetics of EGCG and CAF results showed that the adsorption followed the pseudo-second-order kinetic model. The results also indicated that the equilibrium adsorption data best fit the Langmuir model. Meanwhile, EGCG and CAF were separated successfully onto P4 adsorbents packed columns in a gradient eluent process, and P4 adsorbents exhibited the size exclusion effect for small molecules CAF. Based on the phenolic hydroxyl group and size exclusion effect of P4 adsorbents, the high purity EGCG and CAF were obtained with 40% (v/v) ethanol eluent successively. The process fulfilled the task of simultaneous separation and purification of EGCG and CAF, and proved to be a promising basis for preparations of difficult to obtain active components that have similar polarity and different sizes of molecules and derived from the same natural products. Copyright © 2016 Elsevier B.V. All rights reserved.

Epigallocatechin-3-Gallate Reduces Neuronal Apoptosis in Rats after Middle Cerebral Artery Occlusion Injury via PI3K/AKT/eNOS Signaling Pathway

PubMed Central

Zhonghang, Xu; Tongtong, Liu; Wanshu, Guo

2018-01-01

Background/Aims Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. Methods Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL. Oxidative stress and brain injury markers were examined using ELISA. Apoptosis-related proteins and PI3K/AKT/eNOS signaling pathway were determined using western blot assay and immunohistochemistry. Results EGCG decreased neurological function score, protected nerve cells, inhibited neuronal apoptosis, and inhibited oxidative stress injury and brain injury markers level after MCAO. EGCG reduced the apoptotic rate of neurons, increased the expression of Bcl-2, and decreased the expression of Caspase-3 and Bax. After LY294002 suppressed the PI3K pathway, the protective effect of EGCG decreased after administration of PI3K inhibitors. Conclusion EGCG has a protective effect on rat brain injury induced by MCAO, possibly by modulating the PI3K/AKT/eNOS signaling pathway. PMID:29770336

Effect of epigallocatechin gallate on growth performance and antioxidant capacity in heat-stressed broilers.

PubMed

Xue, Bo; Song, Jiao; Liu, Longzhou; Luo, Jingxian; Tian, Guangming; Yang, Ye

2017-10-01

This study investigated the effects of epigallocatechin gallate (EGCG) on the growth performance and antioxidant capacity of 35-d-old broilers exposed to heat stress. Broilers, 14 d of age, were divided into four groups with six replicates per group (eight chickens/replicate). Thermoneutral group (Group TN) was fed the basal diet and maintained at 28°C for 24 h/d. The heat-stressed groups were housed at 35°C for 12 h/d and 28°C for 12 h/d and fed the basal diet supplemented with EGCG at 0, 300 and 600 mg/kg diet (Groups HS0, HS 300 and HS600, respectively). Compared with Group TN, heat-stressed groups showed significantly reduced gain, feed intake and serum total protein and glucose levels; inhibited serum alkaline phosphatase activities; and increased serum levels of uric acid, cholesterol and triglycerides and the activity of serum creatine kinase, lactate dehydrogenase and aspartate aminotransferase (p < 0.05). Compared with Group HS0, Group HS600 exhibited an increased gain and feed intake; and normalised blood parameters and enzyme activities. Compared with Group TN, the expression of antioxidant-related liver proteins was decreased in Group HS0 and increased in Groups HS300 and HS600 (p < 0.05). The results suggest that EGCG can improve the growth performance and alleviate the oxidant damage by modulating the antioxidant properties of broilers.

Inhibitory effects of (-)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type 1 (HIV-1).

PubMed

Yamaguchi, Koushi; Honda, Mitsuo; Ikigai, Hajime; Hara, Yukihiko; Shimamura, Tadakatsu

2002-01-01

Epigallocatechin gallate (EGCg), the major tea catechin, is known as a potent anti-bacterial agent. In addition, anti-tumor promoting, anti-inflammatory, anti-oxidative and antiviral activities have been reported. In the present study, we investigated possible anti-human immunodeficiency virus type-1 (HIV-1) activity of EGCg and its mechanisms of action in the viral life cycle. EGCg impinges on each step of the HIV life cycle. Thus, destruction of the viral particles, viral attachment to cells, post-adsorption entry into cells, reverse transcription (RT), viral production from chronically-infected cells, and the level of expression of viral mRNA, were analyzed using T-lymphoid (H9) and monocytoid (THP-1) cell systems, and antiviral protease activity was measured using a cell-free assay. Inhibitory effects of EGCg on specific binding of the virions to the cellular surfaces and changes in the steady state viral regulation (mRNA expression) due to EGCg were not observed. However, EGCg had a destructive effect on the viral particles, and post-adsorption entry and RT in acutely infected monocytoid cells were significantly inhibited at concentrations of EGCg greater than 1 microM, and protease kinetics were suppressed at a concentration higher than 10 microM in the cell-free study. Viral production by THP-1 cells chronically-infected with HIV-1 was also inhibited in a dose-dependent manner and the inhibitory effect was enhanced by liposome modification of EGCg. As expected, increased viral mRNA production was observed in lipopolysaccharide (LPS)-activated chronically HIV-1-infected cells. This production was significantly inhibited by EGCg treatment of THP-1 cells. In contrast, production of HIV-1 viral mRNA in unstimulated or LPS-stimulated T-lymphoid cells (H9) was not inhibited by EGCg. Anti-HIV viral activity of EGCg may thus result from an interaction with several steps in the HIV-1 life cycle.

Degradation kinetics of chlorogenic acid at various pH values and effects of ascorbic acid and epigallocatechin gallate on its stability under alkaline conditions.

PubMed

Narita, Yusaku; Inouye, Kuniyo

2013-01-30

5-Caffeoylquinic acid (5-CQA) is generally referred to as chlorogenic acid and exhibits various biological activities such as antioxidant activity and porcine pancreas α-amylase inhibitory activities. 5-CQA may be useful as an antioxidant for food and to prevent diabetes and obesity. The degradation of 5-CQA and caffeic acid (CA) in an aqueous solution at 37 °C and pH 5.0-9.0 was studied. The degradation of 5-CQA and CA, demonstrating time and pH dependence (i.e., the rate constant, k, was higher at higher pH), was satisfactorily described by the Weibull equation. The stability of 5-CQA at pH 7.4 and 9.0 was improved by adding (-)-epigallocatechin gallate (EGCG) and ascorbic acid (AA). Moreover, the degradation of 5-CQA in the presence of EGCG or AA could be described by the Weibull equation. The k value in the presence of EGCG or AA was dependent on their concentration.

Effects of prolonged ingestion of epigallocatechin gallate on diabetes type 1-induced vascular modifications in the erectile tissue of rats.

PubMed

Lombo, C; Morgado, C; Tavares, I; Neves, D

2016-07-01

Diabetes Mellitus type 1 is a metabolic disease that predisposes to erectile dysfunction, partly owing to structural and molecular changes in the corpus cavernosum (CC) vessels. The aim of this study was to determine the effects of early treatment with the antioxidant epigallocatechin gallate (EGCG) in cavernous diabetes-induced vascular modifications. Diabetes was induced in two groups of young Wistar rats; one group was treated with EGCG for 10 weeks. A reduction in smooth muscle content was observed in the CC of diabetic rats, which was significantly attenuated with EGCG consumption. No differences were observed among groups, neither in the expression of VEGF assayed by western blotting nor in the immunofluorescent labeling of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2). VEGFR2 was restricted to the endothelium, whereas VEGF and VEGFR1 co-localized in the smooth muscle layer. With regard to the Angiopoietin/Tie-2 system, no quantitative differences in Angiopoietin 1 were observed among the experimental groups. Ang1 localization was restricted to the smooth muscle layer, and receptor Tie2 and Angiopoietin 2 were both expressed in the endothelium. In brief, our results suggest that EGCG consumption prevented diabetes-induced loss of cavernous smooth muscle but does not affect vascular growth factor expression in young rats.

Epigallocatechin-3-gallate induces oxidative phosphorylation by activating cytochrome c oxidase in human cultured neurons and astrocytes

PubMed Central

Castellano-González, Gloria; Pichaud, Nicolas; Ballard, J. William O.; Bessede, Alban; Marcal, Helder; Guillemin, Gilles J.

2016-01-01

Mitochondrial dysfunction and resulting energy impairment have been identified as features of many neurodegenerative diseases. Whether this energy impairment is the cause of the disease or the consequence of preceding impairment(s) is still under discussion, however a recovery of cellular bioenergetics would plausibly prevent or improve the pathology. In this study, we screened different natural molecules for their ability to increase intracellular adenine triphosphate purine (ATP). Among them, epigallocatechin-3-gallate (EGCG), a polyphenol from green tea, presented the most striking results. We found that it increases ATP production in both human cultured astrocytes and neurons with different kinetic parameters and without toxicity. Specifically, we showed that oxidative phosphorylation in human cultured astrocytes and neurons increased at the level of the routine respiration on the cells pre-treated with the natural molecule. Furthermore, EGCG-induced ATP production was only blocked by sodium azide (NaN3) and oligomycin, inhibitors of cytochrome c oxidase (CcO; complex IV) and ATP synthase (complex V) respectively. These findings suggest that the EGCG modulates CcO activity, as confirmed by its enzymatic activity. CcO is known to be regulated differently in neurons and astrocytes. Accordingly, EGCG treatment is acting differently on the kinetic parameters of the two cell types. To our knowledge, this is the first study showing that EGCG promotes CcO activity in human cultured neurons and astrocytes. Considering that CcO dysfunction has been reported in patients having neurodegenerative diseases such as Alzheimer's disease (AD), we therefore suggest that EGCG could restore mitochondrial function and prevent subsequent loss of synaptic function. PMID:26760769

Effects of fluoride and epigallocatechin gallate on soft-drink-induced dental erosion of enamel and root dentin.

PubMed

Wang, Yin-Lin; Chang, Hao-Hueng; Chiang, Yu-Chih; Lu, Yu-Chen; Lin, Chun-Pin

2018-04-01

Fluoride and epigallocatechin gallate (EGCG) have been proven to prevent dental caries. The purpose of this study was to evaluate the effects of fluoride and EGCG on soft-drink-induced dental erosion in vitro. Forty enamel and dentin specimens were prepared from extracted human teeth. The specimens were divided into 4 groups and treated separately with distilled water (as control), 0.5 M sodium fluoride (NF), 400 μM EGCG (EG), and a solution containing 0.5 M NaF and 400 μM EGCG (FG). Cyclic erosive treatment was performed according to the experimental procedures. The specimens were analyzed using laser scanning confocal microscopy, scanning electron microscopy, and a microhardness tester. The data were analyzed using ANOVA and Bonferroni's post hoc test. The significance level was set at 5%. The amount of substance loss was lower in the NF and EG groups than in the control group (p < 0.05). The erosion-caused substance loss was more pronounced in the dentin than in the enamel specimens. Surface microhardness loss was lower in the NF and EG groups than in the control group (p < 0.05). The diameter of the dentinal tubule was wider in the control group than in the NF and EG groups (p < 0.05). No combined effects were observed in the FG group. Both fluoride and EGCG are effective in preventing soft-drink-induced erosion compared with the control group. Fluoride and EGCG may interfere with each other. The mechanisms of the anti-erosive effect need to be explored in the future. Copyright © 2018. Published by Elsevier B.V.

Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery from type 2 diabetic OLETF rat at chronic stage of disease.

PubMed

Matsumoto, Takayuki; Watanabe, Shun; Kawamura, Ryusuke; Taguchi, Kumiko; Kobayashi, Tsuneo

2014-11-24

There is a growing body of evidence suggesting that epigallocatechin gallate (EGCG), a major catechin isolated from green tea, has several beneficial effects, such as anti-oxidant and anti-inflammatory activities. However, whether treatment with EGCG can suppress the endothelin-1 (ET-1)-induced contraction in carotid arteries from type 2 diabetic rats is unknown, especially at the chronic stage of the disease. We hypothesized that long-term treatment with EGCG would attenuate ET-1-induced contractions in type 2 diabetic arteries. Otsuka Long-Evans Tokushima fatty (OLETF) rats (43 weeks old) were treated with EGCG (200 mg/kg/day for 2 months, p.o.), and the responsiveness to ET-1, phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) was measured in common carotid artery (CA) from EGCG-treated and -untreated OLETF rats and control Long-Evans Tokushima Otsuka (LETO) rats. In OLETF rats, EGCG attenuated responsiveness to ET-1 in CA compared to untreated groups. However, EGCG did not alter PE-induced contractions in CA from OLETF rats. In endothelium-denuded arteries, EGCG did not affect ET-1-induced contractions in either the OLETF or LETO group. Acetylcholine-induced relaxation was increased by EGCG treatment in CA from the OLETF group. The expressions of ET receptors, endothelial nitric oxide synthase, superoxide dismutases, and gp91(phox) [an NAD(P)H oxidase component] in CA were not altered by EGCG treatment in either group. Our data suggest that, within the timescale investigated here, EGCG attenuates ET-1-induced contractions in CA from type 2 diabetic rats, and one of the mechanisms may involve normalizing endothelial function. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury?

PubMed

Ruzicka, Jiri; Urdzikova, Lucia Machova; Svobodova, Barbora; Amin, Anubhav G; Karova, Kristyna; Dubisova, Jana; Zaviskova, Kristyna; Kubinova, Sarka; Schmidt, Meic; Jhanwar-Uniyal, Meena; Jendelova, Pavla

2018-01-01

Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining) and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

Prevention of Human Mammary Carcinogenesis.

DTIC Science & Technology

1996-07-01

eicosapentaenoic acid (EPA), indole-3-carbinol (13C), 0-carotene (P3-C), (-) epigallocatechin gallate ( EGCG ) and genistein (GEN) effectively down...Alteration in Cell Cycle Progression of 184-B5/HER Cells by (-) Epigallocatechin Gallate ( EGCG ) status % distribution of cellsb, c- ac Sof treatm enta... epigallocatechin gallate ( EGCG ,a green tea polyphenol), indole-3-carbinol (13C,a plant indole) and genistein (GEN,a soy isoflavone) showed differential

Cellular determinants involving mitochondrial dysfunction, oxidative stress and apoptosis correlate with the synergic cytotoxicity of epigallocatechin-3-gallate and menadione in human leukemia Jurkat T cells.

PubMed

Tofolean, Ioana Teodora; Ganea, Constanta; Ionescu, Diana; Filippi, Alexandru; Garaiman, Alexandru; Goicea, Alexandru; Gaman, Mihnea-Alexandru; Dimancea, Alexandru; Baran, Irina

2016-01-01

We have investigated the growth-suppressive action of epigallocatechin-3-gallate (EGCG) on human leukemia Jurkat T cells. Results show a strong correlation between the dose-dependent reduction of clonogenic survival following acute EGCG treatments and the EGCG-induced decline of the mitochondrial level of Ca(2+). The cell killing ability of EGCG was synergistically enhanced by menadione. In addition, the cytotoxic effect of EGCG applied alone or in combination with menadione was accompanied by apoptosis induction. We also observed that in acute treatments EGCG displays strong antioxidant properties in the intracellular milieu, but concurrently triggers some oxidative stress generating mechanisms that can fully develop on a longer timescale. In parallel, EGCG dose-dependently induced mitochondrial depolarization during exposure, but this condition was subsequently reversed to a persistent hyperpolarized mitochondrial state that was dependent on the activity of respiratory Complex I. Fluorimetric measurements suggest that EGCG is a mitochondrial Complex III inhibitor and indicate that EGCG evokes a specific cellular fluorescence with emission at 400nm and two main excitation bands (at 330nm and 350nm) that may originate from a mitochondrial supercomplex containing dimeric Complex III and dimeric ATP-synthase, and therefore could provide a valuable means to characterize the functional properties of the respiratory chain. Copyright © 2015 Elsevier Ltd. All rights reserved.

A derivative of epigallocatechin-3-gallate induces apoptosis via SHP-1-mediated suppression of BCR-ABL and STAT3 signalling in chronic myelogenous leukaemia

PubMed Central

Jung, Ji Hoon; Yun, Miyong; Choo, Eun-Jeong; Kim, Sun-Hee; Jeong, Myoung-Seok; Jung, Deok-Beom; Lee, Hyemin; Kim, Eun-Ok; Kato, Nobuo; Kim, Bonglee; Srivastava, Sanjay K; Kaihatsu, Kunihiro; Kim, Sung-Hoon

2015-01-01

Background and Purpose Epigallocatechin-3-gallate (EGCG) is a component of green tea known to have chemo-preventative effects on several cancers. However, EGCG has limited clinical application, which necessitates the development of a more effective EGCG prodrug as an anticancer agent. Experimental Approach Derivatives of EGCG were evaluated for their stability and anti-tumour activity in human chronic myeloid leukaemia (CML) K562 and KBM5 cells. Key Results EGCG-mono-palmitate (EGCG-MP) showed most prolonged stability compared with other EGCG derivatives. EGCG-MP exerted greater cytotoxicity and apoptosis in K562 and KBM5 cells than the other EGCG derivatives. EGCG-MP induced Src-homology 2 domain-containing tyrosine phosphatase 1 (SHP-1) leading decreased oncogenic protein BCR-ABL and STAT3 phosphorylation in CML cells, compared with treatment with EGCG. Furthermore, EGCG-MP reduced phosphorylation of STAT3 and survival genes in K562 cells, compared with EGCG. Conversely, depletion of SHP-1 or application of the tyrosine phosphatase inhibitor pervanadate blocked the ability of EGCG-MP to suppress phosphorylation of BCR-ABL and STAT3, and the expression of survival genes downstream of STAT3. In addition, EGCG-MP treatment more effectively suppressed tumour growth in BALB/c athymic nude mice compared with untreated controls or EGCG treatment. Immunohistochemistry revealed increased caspase 3 and SHP-1 activity and decreased phosphorylation of BCR-ABL in the EGCG-MP-treated group relative to that in the EGCG-treated group. Conclusions and Implications EGCG-MP induced SHP-1-mediated inhibition of BCR-ABL and STAT3 signalling in vitro and in vivo more effectively than EGCG. This derivative may be a potent chemotherapeutic agent for CML treatment. PMID:25825203

Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting β-catenin signaling.

PubMed

Singh, Tripti; Katiyar, Santosh K

2013-12-01

The green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that β-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on β-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and increased cell death and that these cytotoxic effects were associated with inactivation of β-catenin signaling. Evidence of EGCG-induced inactivation of β-catenin included: (i) reduced accumulation of nuclear β-catenin; (ii) enhanced levels of casein kinase1α, reduced phosphorylation of glycogen synthase kinase-3β, and increased phosphorylation of β-catenin on critical serine(45,33/37) residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9, which are down-stream targets of β-catenin. Treatment of cells with prostaglandin E2 (PGE2) enhanced the accumulation of β-catenin and enhanced β-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809) reduced the PGE2-enhanced levels of cAMP, an upstream regulator of β-catenin. Inactivation of β-catenin by EGCG resulted in suppression of cell survival signaling proteins. siRNA knockdown of β-catenin in A431 and SCC13 cells reduced cell viability. Collectively, these data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of β-catenin signaling and that the β-catenin signaling is upregulated by inflammatory mediators. © 2013.

Epigallocatechin Gallate-Loaded Gelatin-g-Poly(N-Isopropylacrylamide) as a New Ophthalmic Pharmaceutical Formulation for Topical Use in the Treatment of Dry Eye Syndrome.

PubMed

Luo, Li-Jyuan; Lai, Jui-Yang

2017-08-24

Given that biodegradable in situ gelling delivery systems may have potential applications in the design of ophthalmic pharmaceutical formulations, this study, for the first time, aims to develop gelatin-g-poly(N-isopropylacrylamide) (GN) carriers for topical epigallocatechin gallate (EGCG) administration in the treatment of dry eye disease (DED). By temperature triggered sol-gel phase transition of copolymers, EGCG-loaded GN was prepared at 32 °C and characterized by FTIR, NMR, and HPLC analyses. Results of WST-1 and live/dead assays showed that GN materials have good compatibility with corneal epithelial cells. Gradual biodegradation of delivery carriers allowed sustained release of EGCG without drug toxicity. Anti-inflammatory and antioxidant activity studies also indicated effective therapeutic drug levels at each time point within 3 days of release. In a rabbit dry eye model, corneal epithelial defects was ameliorated by treatment with single-dose administration of EGCG-containing GN. Furthermore, drug molecules released from carrier materials could prevent further tear evaporation and loss of mucin-secreting goblet cells in diseased animals. Our findings suggest that GN carrier is responsible for enhanced pharmacological efficacy of topically instilled EGCG, thereby demonstrating the benefits of using biodegradable in situ gelling delivery system to overcome the drawbacks of limited dry eye relief associated with eye drop dosage form.

Coencapsulation of (-)-Epigallocatechin-3-gallate and Quercetin in Particle-Stabilized W/O/W Emulsion Gels: Controlled Release and Bioaccessibility.

PubMed

Chen, Xing; McClements, David Julian; Wang, Jian; Zou, Liqiang; Deng, Sumeng; Liu, Wei; Yan, Chi; Zhu, Yuqing; Cheng, Ce; Liu, Chengmei

2018-04-11

Particle-stabilized W 1 /O/W 2 emulsion gels were fabricated using a two-step procedure: ( i) a W 1 /O emulsion was formed containing saccharose (for osmotic stress balance) and gelatin (as a gelling agent) in the aqueous phase and polyglycerol polyricinoleate (a lipophilic surfactant) in the oil phase; ( ii) this W 1 /O emulsion was then homogenized with another water phase (W 2 ) containing wheat gliadin nanoparticles (hydrophilic emulsifier). The gliadin nanoparticles in the external aqueous phase aggregated at pH 5.5, which led to the formation of particle-stabilized W 1 /O/W 2 emulsion gels with good stability to phase separation. These emulsion gels were then used to coencapsulate a hydrophilic bioactive (epigallocatechin-3-gallate, EGCG) in the internal aqueous phase (encapsulation efficiency = 65.5%) and a hydrophobic bioactive (quercetin) in the oil phase (encapsulation efficiency = 97.2%). The emulsion gels improved EGCG chemical stability and quercetin solubility under simulated gastrointestinal conditions, which led to a 2- and 4-fold increase in their effective bioaccessibility, respectively.

EGCG inhibit chemical reactivity of iron through forming an Ngal-EGCG-iron complex.

PubMed

Bao, Guan-Hu; Xu, Jie; Hu, Feng-Lin; Wan, Xiao-Chun; Deng, Shi-Xian; Barasch, Jonathan

2013-12-01

Accumulated evidence indicates that the interconversion of iron between ferric (Fe(3+)) and ferrous (Fe(2+)) can be realized through interaction with reactive oxygen species in the Fenton and Haber-Weiss reactions and thereby physiologically effects redox cycling. The imbalance of iron and ROS may eventually cause tissue damage such as renal proximal tubule injury and necrosis. Many approaches were exploited to ameliorate the oxidative stress caused by the imbalance. (-)-Epigallocatechin-3-gallate, the most active and most abundant catechin in tea, was found to be involved in the protection of a spectrum of renal injuries caused by oxidative stress. Most of studies suggested that EGCG works as an antioxidant. In this paper, Multivariate analysis of the LC-MS data of tea extracts and binding assays showed that the tea polyphenol EGCG can form stable complex with iron through the protein Ngal, a biomarker of acute kidney injury. UV-Vis and Luminescence spectrum methods showed that Ngal can inhibit the chemical reactivity of iron and EGCG through forming an Ngal-EGCG-iron complex. In thinking of the interaction of iron and ROS, we proposed that EGCG may work as both antioxidant and Ngal binding siderphore in protection of kidney from injuries.

Differential prooxidative effects of the green tea polyphenol, (-)-epigallocatechin-3-gallate, in normal and oral cancer cells are related to differences in sirtuin 3 signaling.

PubMed

Tao, Ling; Park, Jong-Yung; Lambert, Joshua D

2015-02-01

We have previously reported that the green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), can induce oxidative stress in oral cancer cells but exerts antioxidant effects in normal cells. Here, we report that these differential prooxidative effects are associated with sirtuin 3 (SIRT3), an important mitochondrial redox modulator. EGCG rapidly induced mitochondria-localized reactive oxygen species in human oral squamous carcinoma cells (SCC-25, SCC-9) and premalignant leukoplakia cells (MSK-Leuk1), but not in normal human gingival fibroblast cells (HGF-1). EGCG suppressed SIRT3 mRNA and protein expression, as well as, SIRT3 activity in SCC-25 cells, whereas it increased SIRT3 activity in HGF-1 cells. EGCG selectively decreased the nuclear localization of the estrogen-related receptor α (ERRα), the transcription factor regulating SIRT3 expression, in SCC-25 cells. This indicates that EGCG may regulate SIRT3 transcription in oral cancer cells via ERRα. EGCG also differentially modulated the mRNA expressions of SIRT3-associated downstream targets including glutathione peroxidase 1 and superoxide dismutase 2 in normal and oral cancer cells. SIRT3 represents a novel potential target through which EGCG exerts differential prooxidant effects in cancer and normal cells. Our results provide new biomarkers to be further explored in animal studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Major Green Tea Polyphenol, (−)-Epigallocatechin-3-Gallate, Inhibits Obesity, Metabolic Syndrome, and Fatty Liver Disease in High-Fat–Fed Mice1,2

PubMed Central

Bose, Mousumi; Lambert, Joshua D.; Ju, Jihyeung; Reuhl, Kenneth R.; Shapses, Sue A.; Yang, Chung S.

2008-01-01

In this study, we investigated the effects of the major green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), on high-fat–induced obesity, symptoms of the metabolic syndrome, and fatty liver in mice. In mice fed a high-fat diet (60% energy as fat), supplementation with dietary EGCG treatment (3.2 g/kg diet) for 16 wk reduced body weight (BW) gain, percent body fat, and visceral fat weight (P < 0.05) compared with mice without EGCG treatment. The BW decrease was associated with increased fecal lipids in the high-fat–fed groups (r2 = 0.521; P < 0.05). EGCG treatment attenuated insulin resistance, plasma cholesterol, and monocyte chemoattractant protein concentrations in high-fat–fed mice (P < 0.05). EGCG treatment also decreased liver weight, liver triglycerides, and plasma alanine aminotransferase concentrations in high-fat–fed mice (P < 0.05). Histological analyses of liver samples revealed decreased lipid accumulation in hepatocytes in mice treated with EGCG compared with high-fat diet-fed mice without EGCG treatment. In another experiment, 3-mo-old high-fat–induced obese mice receiving short-term EGCG treatment (3.2 g/kg diet, 4 wk) had decreased mesenteric fat weight and blood glucose compared with high-fat–fed control mice (P < 0.05). Our results indicate that long-term EGCG treatment attenuated the development of obesity, symptoms associated with the metabolic syndrome, and fatty liver. Short-term EGCG treatment appeared to reverse preexisting high-fat–induced metabolic pathologies in obese mice. These effects may be mediated by decreased lipid absorption, decreased inflammation, and other mechanisms. PMID:18716169

Role of (-)-epigallocatechin gallate in the pharmacokinetic interaction between nadolol and green tea in healthy volunteers.

PubMed

Abe, Osamu; Ono, Tomoyuki; Sato, Hideyuki; Müller, Fabian; Ogata, Hiroshi; Miura, Itaru; Shikama, Yayoi; Yabe, Hirooki; Onoue, Satomi; Fromm, Martin F; Kimura, Junko; Misaka, Shingen

2018-06-01

The aim of the present study is to investigate a possible role of a single dose of (-)-epigallocatechin gallate (EGCG), the major catechin in green tea, for the pharmacokinetic interaction between green tea and nadolol in humans. In a randomized three-phase crossover study, 13 healthy volunteers received single doses of 30 mg nadolol orally with water (control), or an aqueous solution of EGCG-concentrated green tea extract (GTE) at low or high dose. Plasma concentrations and urinary excretion of nadolol were determined up to 48 h. In addition, blood pressure and pulse rate were monitored. In vitro transport kinetic experiments were performed using human embryonic kidney 293 cells stably expressing organic anion transporting polypeptide (OATP)1A2 to evaluate the inhibitory effect of EGCG on OATP1A2-mediated substrate transport. Single coadministration of low and high dose GTE significantly reduced the plasma concentrations of nadolol. The geometric mean ratios with 90% CI for area under the plasma concentration-time curves from 0 to infinity of nadolol were 0.72 (0.56-0.87) for the low and 0.60 (0.51-0.69) for the high dose. There were no significant differences in T max , elimination half-life, and renal clearance between GTE and water phases. No significant changes were observed for blood pressure and pulse rate between phases. EGCG competitively inhibited OATP1A2-mediated uptake of sulphobromophthalein and nadolol with K i values of 21.6 and 19.4 μM, respectively. EGCG is suggested to be a key contributor to the interaction of green tea with nadolol. Moreover, even a single coadministration of green tea may significantly affect nadolol pharmacokinetics.

Blood brain barrier permeability of (-)-epigallocatechin gallate, its proliferation-enhancing activity of human neuroblastoma SH-SY5Y cells, and its preventive effect on age-related cognitive dysfunction in mice.

PubMed

Pervin, Monira; Unno, Keiko; Nakagawa, Aimi; Takahashi, Yuu; Iguchi, Kazuaki; Yamamoto, Hiroyuki; Hoshino, Minoru; Hara, Aya; Takagaki, Akiko; Nanjo, Fumio; Minami, Akira; Imai, Shinjiro; Nakamura, Yoriyuki

2017-03-01

The consumption of green tea catechins (GTCs) suppresses age-related cognitive dysfunction in mice. GTCs are composed of several catechins, of which epigallocatechin gallate (EGCG) is the most abundant, followed by epigallocatechin (EGC). Orally ingested EGCG is hydrolyzed by intestinal biota to EGC and gallic acid (GA). To understand the mechanism of action of GTCs on the brain, their permeability of the blood brain barrier (BBB) as well as their effects on cognitive function in mice and on nerve cell proliferation in vitro were examined. The BBB permeability of EGCG, EGC and GA was examined using a BBB model kit. SAMP10, a mouse model of brain senescence, was used to test cognitive function in vivo . Human neuroblastoma SH-SY5Y cells were used to test nerve cell proliferation and differentiation. The in vitro BBB permeability (%, in 30 min) of EGCG, EGC and GA was 2.8±0.1, 3.4±0.3 and 6.5±0.6, respectively. The permeability of EGCG into the BBB indicates that EGCG reached the brain parenchyma even at a very low concentration. The learning ability of SAMP10 mice that ingested EGCG (20 mg/kg) was significantly higher than of mice that ingested EGC or GA. However, combined ingestion of EGC and GA showed a significant improvement comparable to EGCG. SH-SY5Y cell growth was significantly enhanced by 0.05 µM EGCG, but this effect was reduced at higher concentrations. The effect of EGC and GA was lower than that of EGCG at 0.05 µM. Co-administration of EGC and GA increased neurite length more than EGC or GA alone. Cognitive dysfunction in mice is suppressed after ingesting GTCs when a low concentration of EGCG is incorporated into the brain parenchyma via the BBB. Nerve cell proliferation/differentiation was enhanced by a low concentration of EGCG. Furthermore, the additive effect of EGC and GA suggests that EGCG sustains a preventive effect after the hydrolysis to EGC and GA.

Epigallocatechin-3-gallate Ameliorates Seawater Aspiration-Induced Acute Lung Injury via Regulating Inflammatory Cytokines and Inhibiting JAK/STAT1 Pathway in Rats

PubMed Central

Liu, Wei; Dong, Mingqing; Bo, Liyan; Li, Congcong; Liu, Qingqing; Li, Yanyan; Ma, Lijie; Xie, Yonghong; Fu, Enqing; Mu, Deguang; Pan, Lei; Jin, Faguang; Li, Zhichao

2014-01-01

Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-α, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-α and IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-α and IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1 in vivo and in vitro and reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats. PMID:24692852

Effects of green tea polyphenol (-)-epigallocatechin-3-gallate on newly developed high-fat/Western-style diet-induced obesity and metabolic syndrome in mice.

PubMed

Chen, Yu-Kuo; Cheung, Connie; Reuhl, Kenneth R; Liu, Anna Ba; Lee, Mao-Jung; Lu, Yao-Ping; Yang, Chung S

2011-11-09

The aim of this study was to investigate the effects of (-)-epigallocatechin-3-gallate (EGCG) on newly developed high-fat/Western-style diet-induced obesity and symptoms of metabolic syndrome. Male C57BL/6J mice were fed a high fat/Western-style (HFW; 60% energy as fat and lower levels of calcium, vitamin D(3), folic acid, choline bitartrate, and fiber) or HFW with EGCG (HFWE; HFW with 0.32% EGCG) diet for 17 wks. As a comparison, two other groups of mice fed a low-fat diet (LF; 10% energy as fat) and high-fat diet (HF; 60% energy as fat) were also included. The HFW group developed more body weight gain and severe symptoms of metabolic syndrome than the HF group. The EGCG treatment significantly reduced body weight gain associated with increased fecal lipids and decreased blood glucose and alanine aminotransferase (ALT) levels compared to those of the HFW group. Fatty liver incidence, liver damage, and liver triglyceride levels were also decreased by the EGCG treatment. Moreover, the EGCG treatment attenuated insulin resistance and levels of plasma cholesterol, monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP), interlukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). Our results demonstrate that the HFW diet produces more severe symptoms of metabolic syndrome than the HF diet and that the EGCG treatment can alleviate these symptoms and body fat accumulation. The beneficial effects of EGCG are associated with decreased lipid absorption and reduced levels of inflammatory cytokines.

Epigallocatechin-3-gallate as a potential therapeutic drug for TTR-related amyloidosis: "in vivo" evidence from FAP mice models.

PubMed

Ferreira, Nelson; Saraiva, Maria João; Almeida, Maria Rosário

2012-01-01

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease caused by the extracellular deposition of mutant transthyretin (TTR), with special involvement of the peripheral nervous system (PNS). Currently, hepatic transplantation is considered the most efficient therapy to halt the progression of clinical symptoms in FAP since more than 95% of TTR is produced by the liver. However, less invasive and more reliable therapeutic approaches have been proposed for FAP therapy, namely based on drugs acting as inhibitors of amyloid formation or as amyloid disruptors. We have recently reported that epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, is able to inhibit TTR aggregation and fibril formation, "in vitro" and in a cellular system, and is also able to disrupt pre-formed amyloid fibrils "in vitro". In the present study, we assessed the effect of EGCG subchronic administration on TTR amyloidogenesis "in vivo", using well characterized animal models for FAP. Semiquantitative immunohistochemistry (SQ-IHC) and Western blot analysis of mice tissues after treatment demonstrated that EGCG inhibits TTR toxic aggregates deposition in about 50% along the gastrointestinal tract (GI) and peripheral nervous system (PNS). Moreover EGCG treatment considerably lowered levels of several biomarkers associated with non-fibrillar TTR deposition, namely endoplasmic reticulum (ER)-stress, protein oxidation and apoptosis markers. Treatment of old FAP mice with EGCG resulted not only in the decrease of non-fibrillar TTR deposition but also in disaggregation of amyloid deposits. Consistently, matrix metalloproteinase (MMP)-9 and serum amyloid P component (SAP), both markers of amyloid deposition, were also found reduced in treated old FAP mice. The dual effect of EGCG both as TTR aggregation inhibitor and amyloid fibril disruptor together with the high tolerability and low toxicity of EGCG in humans, point towards the potential use of this compound, or

Effect of epigallocatechin-3-gallate, major ingredient of green tea, on the pharmacokinetics of rosuvastatin in healthy volunteers

PubMed Central

Kim, Tae-Eun; Ha, Na; Kim, Yunjeong; Kim, Hyunsook; Lee, Jae Wook; Jeon, Ji-Young; Kim, Min-Gul

2017-01-01

Previous in vitro studies have demonstrated the inhibitory effect of green tea on drug transporters. Because rosuvastatin, a lipid-lowering drug widely used for the prevention of cardiovascular events, is a substrate for many drug transporters, there is a possibility that there is interaction between green tea and rosuvastatin. The aim of this study was to investigate the effect of green tea on the pharmacokinetics of rosuvastatin in healthy volunteers. An open-label, three-treatment, fixed-sequence study was conducted. On Day 1, 20 mg of rosuvastatin was given to all subjects. After a 3-day washout period, the subjects received 20 mg of rosuvastatin plus 300 mg of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea (Day 4). After a 10-day pretreatment of EGCG up to Day 14, they received rosuvastatin (20 mg) plus EGCG (300 mg) once again (Day 15). Blood samples for the pharmacokinetic assessments were collected up to 8 hours after each dose of rosuvastatin. A total of 13 healthy volunteers were enrolled. Compared with the administration of rosuvastatin alone, the concomitant use at Day 4 significantly reduced the area under the concentration–time curve from time 0 to the last measurable time (AUClast) by 19% (geometric mean ratio 0.81, 90% confidence interval [CI] 0.67–0.97) and the peak plasma concentration (Cmax) by 15% (geometric mean ratio 0.85, 90% CI 0.70–1.04). AUClast or Cmax of rosuvastatin on Day 15 was not significantly different from that on Day 1. This study demonstrated that co-administration of EGCG reduces the systemic exposure of rosuvastatin by 19%, and pretreatment of EGCG can eliminate that effect of co-administration of EGCG. PMID:28533679

Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages.

PubMed

Wang, Qi-Ming; Wang, Hao; Li, Ya-Fei; Xie, Zhi-Yong; Ma, Yao; Yan, Jian-Jun; Gao, Yi Fan Wei; Wang, Ze-Mu; Wang, Lian-Sheng

2016-01-01

It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque. © 2016 The Author(s) Published by S. Karger AG, Basel.

(-)-Epigallocatechin 3-Gallate Synthetic Analogues Inhibit Fatty Acid Synthase and Show Anticancer Activity in Triple Negative Breast Cancer.

PubMed

Crous-Masó, Joan; Palomeras, Sònia; Relat, Joana; Camó, Cristina; Martínez-Garza, Úrsula; Planas, Marta; Feliu, Lidia; Puig, Teresa

2018-05-11

(-)-Epigallocatechin 3-gallate (EGCG) is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN), which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC) cells. All compounds displayed moderate to high cytotoxicity and significantly blocked FASN activity, monoesters M1 and M2 being more potent inhibitors than diesters. Interestingly, G28, M1, and M2 also diminished FASN protein expression levels, but only monoesters M1 and M2 induced apoptosis. Our results indicate that FASN inhibition by such polyphenolic compounds could be a new strategy in TNBC treatment, and highlight the potential anticancer activities of monoesters. Thus, G28, G37, G56, and most importantly M1 and M2, are anticancer candidates (alone or in combination) to be further characterized in vitro and in vivo.

Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration.

PubMed

Karthikeyan, Bose; Harini, Lakshminarasimhan; Krishnakumar, Vaithilingam; Kannan, Velu Rajesh; Sundar, Krishnan; Kathiresan, Thandavarayan

2017-01-01

Endoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in the pathogenesis of age-related macular degeneration (AMD). ER stress leads to accumulation of misfolded proteins, which in turn activates unfolded protein response (UPR) of the cell for its survival. The prolonged UPR of ER stress promotes cell death; however, the transition between adaptation and ER stress-induced apoptosis has not been clearly understood. Hence, the present study investigates the regulatory effect of (-)-epigallocatechin gallate (EGCG) on ER stress-induced by hydrogen peroxide (H 2 O 2 ) and disturbance of calcium homeostasis by thapsigargin (TG) in mouse retinal pigment epithelial (MRPE) cells. The oxidant molecules influenced MRPE cells showed an increased level of intracellular calcium [Ca 2+ ] i in ER and transferred to mitochondria through ER-mitochondrial tether site then increased ROS production. EGCG restores [Ca 2+ ] i homeostasis by decreasing ROS production through inhibition of prohibitin1 which regulate ER-mitochondrial tether site and inhibit apoptosis. Effect of EGCG on ER stress-mediated apoptosis was elucidated by exploring the UPR signalling pathways. EGCG downregulated GRP78, CHOP, PERK, ERO1α, IRE1α, cleaved PARP, cleaved caspase 3, caspase 12 and upregulated expression of calnexinin MRPE cells. In addition to this, inhibition of apoptosis by EGCG was also confirmed with expression of proteins Akt, PTEN and GSK3β. MRPE cells with EGCG upregulates phosphorylation of Akt at ser473 and phospho ser380 of PTEN, but phosphorylation at ser9 of GSK3β was inhibited. Further, constitutively active (myristoylated) CA-Akt transfected in MRPE cells had an increased Akt activity in EGCG influenced cells. These findings strongly suggest that antioxidant molecules inhibit cell death through the proper balancing of [Ca 2+ ] i and ROS production in order to maintain UPR of ER in MRPE cells. Thus, modulation of UPR signalling may provide a potential target for

Epigallocatechin-3-gallate improves cardiac hypertrophy and short-term memory deficits in a Williams-Beuren syndrome mouse model

PubMed Central

Bosch-Morató, Mònica; Guivernau, Biuse; Albericio, Guillermo; Muñoz, Francisco J.; Pérez-Jurado, Luis A.

2018-01-01

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a heterozygous deletion of 26–28 genes at chromosome band 7q11.23. The complete deletion (CD) mouse model mimics the most common deletion found in WBS patients and recapitulates most neurologic features of the disorder along with some cardiovascular manifestations leading to significant cardiac hypertrophy with increased cardiomyocytes’ size. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, has been associated with potential health benefits, both on cognition and cardiovascular phenotypes, through several mechanisms. We aimed to investigate the effects of green tea extracts on WBS-related phenotypes through a phase I clinical trial in mice. After feeding CD animals with green tea extracts dissolved in the drinking water, starting at three different time periods (prenatal, youth and adulthood), a set of behavioral tests and several anatomical, histological and molecular analyses were performed. Treatment resulted to be effective in the reduction of cardiac hypertrophy and was also able to ameliorate short-term memory deficits of CD mice. Taken together, these results suggest that EGCG might have a therapeutic and/or preventive role in the management of WBS. PMID:29554110

Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Dongxu; Wang, Yijun; Wan, Xiaochun

(−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1more » (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG

Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled trial.

PubMed

Brown, A Louise; Lane, Joan; Coverly, Jacqueline; Stocks, Janice; Jackson, Sarah; Stephen, Alison; Bluck, Les; Coward, Andy; Hendrickx, Hilde

2009-03-01

Animal evidence indicates that green tea may modulate insulin sensitivity, with epigallocatechin-3-gallate (EGCG) proposed as a likely health-promoting component. The purpose of this study was to investigate the effect of dietary supplementation with EGCG on insulin resistance and associated metabolic risk factors in man. Overweight or obese male subjects, aged 40-65 years, were randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement of metabolic risk factors (BMI, waist circumference, percentage body fat, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted pre- and post-intervention. Mood was evaluated weekly using the University of Wales Institute of Science and Technology mood adjective checklist. EGCG treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo - 0.058 (se 0.75) mmHg; EGCG - 2.68 (se 0.72) mmHg; P = 0.014). No significant change in the other metabolic risk factors was observed. The EGCG group also reported feeling in a more positive mood than the placebo group across the intervention period (mean score for hedonic tone: EGCG, 29.11 (se 0.44); placebo, 27.84 (se 0.46); P = 0.048). In conclusion, regular intake of EGCG had no effect on insulin resistance but did result in a modest reduction in diastolic blood pressure. This antihypertensive effect may contribute to some of the cardiovascular benefits associated with habitual green tea consumption. EGCG treatment also had a positive effect on mood. Further studies are needed to confirm the findings and investigate their mechanistic basis.

The green tea catechin epigallocatechin gallate induces cell cycle arrest and shows potential synergism with cisplatin in biliary tract cancer cells.

PubMed

Mayr, Christian; Wagner, Andrej; Neureiter, Daniel; Pichler, Martin; Jakab, Martin; Illig, Romana; Berr, Frieder; Kiesslich, Tobias

2015-06-23

The green tea catechin epigallocatechin gallate (EGCG) was shown to effectively inhibit tumor growth in various types of cancer including biliary tract cancer (BTC). For most BTC patients only palliative therapy is possible, leading to a median survival of about one year. Chemoresistance is a major problem that contributes to the high mortality rates of BTC. The aim of this study was to investigate the cytotoxic effect of EGCG alone or in combination with cisplatin on eight BTC cell lines and to investigate the cellular anti-cancer mechanisms of EGCG. The effect of EGCG treatment alone or in combination with the standard chemotherapeutic cisplatin on cell viability was analyzed in eight BTC cell lines. Additionally, we analyzed the effects of EGCG on caspase activity, cell cycle distribution and gene expression in the BTC cell line TFK-1. EGCG significantly reduced cell viability in all eight BTC cell lines (p < 0.05 or p < 0.01, respectively, for most cell lines and EGCG concentrations > 5 μM). Combined EGCG and cisplatin treatment showed a synergistic cytotoxic effect in five cell lines and an antagonistic effect in two cell lines. Furthermore, EGCG reduced the mRNA levels of various cell cycle-related genes, while increasing the expression of the cell cycle inhibitor p21 and the apoptosis-related death receptor 5 (p < 0.05). This observation was accompanied by an increase in caspase activity and cells in the sub-G1 phase of the cell cycle, indicating induction of apoptosis. EGCG also induced a down-regulation of expression of stem cell-related genes and genes that are associated with an aggressive clinical character of the tumor, such as cd133 and abcg2. EGCG shows various anti-cancer effects in BTC cell lines and might therefore be a potential anticancer drug for future studies in BTC. Additionally, EGCG displays a synergistic cytotoxic effect with cisplatin in most tested BTC cell lines. Graphical abstract Summary illustration.

Inhibitory effect of the green tea molecule EGCG against dengue virus infection.

PubMed

Raekiansyah, Muhareva; Buerano, Corazon C; Luz, Mark Anthony D; Morita, Kouichi

2018-06-01

Dengue virus (DENV) infection is a major public health problem worldwide; however, specific antiviral drugs against it are not available. Hence, identifying effective antiviral agents for the prevention of DENV infection is important. In this study, we showed that the reportedly highly biologically active green-tea component epigallocatechin gallate (EGCG) inhibited dengue virus infection regardless of infecting serotype, but no or minimal inhibition was observed with other flaviviruses, including Japanese encephalitis virus, yellow fever virus, and Zika virus. EGCG exerted its antiviral effect mainly at the early stage of infection, probably by interacting directly with virions to prevent virus infection. Our results suggest that EGCG specifically targets DENV and might be used as a lead structure to develop an antiviral drug for use against the virus.

Monitoring and Counteracting Functional Deterioration in Parkinson’s Disease: A Multilevel Integrative Approach in a Primate Model System

DTIC Science & Technology

2006-09-01

PD like symptoms (Colisimo et al., 1992; Fukuda, 2001). The effects of Riluzole (anti-excitotoxic) treatment, epigallocatechin -3- gallate ( EGCG ...the dose response study (-)- Epigallocatechin 3-O- gallate ( EGCG ; Teavigo®) was kindly provided bij DSM, Switserland. The anti-excitotoxic compound...2003). " Epigallocatechin gallate modulates CYP450 isoforms in the female Swiss-Webster mouse." Toxicol Sci 76(2): 262-70. Heikkila RE, Cohen G

Mobile phone radiation-induced free radical damage in the liver is inhibited by the antioxidants N-acetyl cysteine and epigallocatechin-gallate.

PubMed

Ozgur, Elcin; Güler, Göknur; Seyhan, Nesrin

2010-11-01

To investigate oxidative damage and antioxidant enzyme status in the liver of guinea pigs exposed to mobile phone-like radiofrequency radiation (RFR) and the potential protective effects of N-acetyl cysteine (NAC) and epigallocatechin-gallate (EGCG) on the oxidative damage. Nine groups of guinea pigs were used to study the effects of exposure to an 1800-MHz Global System for Mobile Communications (GSM)-modulated signal (average whole body Specific Absorption Rate (SAR) of 0.38 W/kg, 10 or 20 min per day for seven days) and treatment with antioxidants. Significant increases in malondialdehyde (MDA) and total nitric oxide (NO(x)) levels and decreases in activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and glutathione peroxidase (GSH-Px) were observed in the liver of guinea pigs after RFR exposure. Only NAC treatment induces increase in hepatic GSH-Px activities, whereas EGCG treatment alone attenuated MDA level. Extent of oxidative damage was found to be proportional to the duration of exposure (P < 0.05). Mobile phone-like radiation induces oxidative damage and changes the activities of antioxidant enzymes in the liver. The adverse effect of RFR may be related to the duration of mobile phone use. NAC and EGCG protect the liver tissue against the RFR-induced oxidative damage and enhance antioxidant enzyme activities.

Mitochondrial Modulation by Epigallocatechin 3-Gallate Ameliorates Cisplatin Induced Renal Injury through Decreasing Oxidative/Nitrative Stress, Inflammation and NF-kB in Mice

PubMed Central

Wang, Xueping; Wang, Ping; Fu, Guanghou; Meng, Hongzhou; Wang, Yimin; Jin, Baiye

2015-01-01

Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for

Epigallocatechin-3-gallate(EGCG) suppresses melanoma cell growth and metastasis by targeting TRAF6 activity.

PubMed

Zhang, Jianglin; Lei, Zhou; Huang, Zunnan; Zhang, Xu; Zhou, Youyou; Luo, Zhongling; Zeng, Weiqi; Su, Juan; Peng, Cong; Chen, Xiang

2016-11-29

TRAF6 (TNF Receptor-Associated Factor 6) is an E3 ubiquitin ligase that contains a Ring domain, induces K63-linked polyubiquitination, and plays a critical role in signaling transduction. Our previous results demonstrated that TRAF6 is overexpressed in melanoma and that TRAF6 knockdown dramatically attenuates tumor cell growth and metastasis. In this study, we found that EGCG can directly bind to TRAF6, and a computational model of the interaction between EGCG and TRAF6 revealed that EGCG probably interacts with TRAF6 at the residues of Gln54, Gly55, Asp57 ILe72, Cys73 and Lys96. Among these amino acids, mutation of Gln54, Asp57, ILe72 in TRAF6 could destroy EGCG bound to TRAF6, furthermore, our results demonstrated that EGCG significantly attenuates interaction between TRAF6 and UBC13(E2) and suppresses TRAF6 E3 ubiquitin ligase activity in vivo and in vitro. Additionally, the phosphorylation of IκBα, p-TAK1 expression are decreased and the nuclear translocation of p65 and p50 is blocked by treatment with EGCG, leading to inactivation of the NF-κB pathway. Moreover, EGCG significantly inhibits cell growth as well as the migration and invasion of melanoma cells. Taken together, these findings show that EGCG is a novel E3 ubiquitin ligase inhibitor that could be used to target TRAF6 for chemotherapy or the prevention of melanoma.

Epigallocatechin gallate targets FTO and inhibits adipogenesis in an mRNA m6A-YTHDF2-dependent manner.

PubMed

Wu, Ruifan; Yao, Yongxi; Jiang, Qin; Cai, Min; Liu, Qing; Wang, Yizhen; Wang, Xinxia

2018-05-24

N 6 -methyladenosine (m 6 A) modification of mRNA plays a role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, plays a critical role in anti-obesity and anti-adipogenesis. High-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HPLC-QqQ-MS/MS) was performed to determine the m 6 A levels in 3T3-L1 preadipocytes. The effects of EGCG on the m 6 A levels in specific genes were determined by methylated RNA immunoprecipitation coupled with quantitative real-time PCR (meRIP-qPCR). Several adipogenesis makers and cell cycle genes were analyzed by quantitative real-time PCR (qPCR) and western blotting. Lipid accumulation was evaluated by oil red O staining. All measurements were performed at least for three times. Here we showed that EGCG inhibited adipogenesis by blocking the mitotic clonal expansion (MCE) at the early stage of adipocyte differentiation. Exposing 3T3-L1 cells to EGCG reduced the expression of fat mass and obesity-associated (FTO) protein, an m 6 A demethylase, which led to increased overall levels of RNA m 6 A methylation. Cyclin A2 (CCNA2) and cyclin dependent kinase 2 (CDK2) play vital roles in MCE. The m 6 A levels of CCNA2 and CDK2 mRNA were dramatically enhanced by EGCG. Interestingly, EGCG increased the expression of YTH N 6 -methyladenosine RNA binding protein 2 (YTHDF2), which recognized and decayed methylated mRNAs, resulting in decreased protein levels of CCNA2 and CDK2. As a result, MCE was blocked and adipogenesis was inhibited. FTO overexpression and YTHDF2 knockdown in 3T3-L1 cells significantly increased CCNA2 and CDK2 protein levels and ameliorated the EGCG-induced adipogenesis inhibition. Thus, m 6 A-dependent CCNA2 and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition. Our findings provide mechanistic insights into how m 6 A is involved in the

Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled trial

PubMed Central

Brown, A. Louise; Lane, Joan; Coverly, Jacqueline; Stocks, Janice; Jackson, Sarah; Stephen, Alison; Bluck, Les; Coward, Andy; Hendrickx, Hilde

2010-01-01

Animal evidence indicates that green tea may modulate insulin sensitivity, with epigallocatechin-3-gallate (EGCG) proposed as a likely health-promoting component. The purpose of this study was to investigate the effect of dietary supplementation with EGCG on insulin resistance and associated metabolic risk factors in man. Overweight or obese male subjects, aged 40–65 years, were randomly assigned to take 400 mg capsules of EGCG (n 46) or the placebo lactose (n 42), twice daily for 8 weeks. Oral glucose tolerance testing and measurement of metabolic risk factors (BMI, waist circumference, percentage body fat, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG) was conducted pre- and post-intervention. Mood was evaluated weekly using the University of Wales Institute of Science and Technology mood adjective checklist. EGCG treatment had no effect on insulin sensitivity, insulin secretion or glucose tolerance but did reduce diastolic blood pressure (mean change: placebo −0·058 (SE 0·75) mmHg; EGCG −2·68 (SE 0·72) mmHg; P=0·014). No significant change in the other metabolic risk factors was observed. The EGCG group also reported feeling in a more positive mood than the placebo group across the intervention period (mean score for hedonic tone: EGCG, 29·11 (SE 0·44); placebo, 27·84 (SE 0·46); P=0·048). In conclusion, regular intake of EGCG had no effect on insulin resistance but did result in a modest reduction in diastolic blood pressure. This antihypertensive effect may contribute to some of the cardiovascular benefits associated with habitual green tea consumption. EGCG treatment also had a positive effect on mood. Further studies are needed to confirm the findings and investigate their mechanistic basis. PMID:18710606

Epigallocatechin-3-gallate attenuates acute and chronic psoriatic itch in mice: Involvement of antioxidant, anti-inflammatory effects and suppression of ERK and Akt signaling pathways.

PubMed

Guo, Ran; Zhou, Feng-Ming; Su, Cun-Jin; Liu, Teng-Teng; Zhou, Yan; Fan, Li; Wang, Zhi-Hong; Liu, Xu; Huang, Ya; Liu, Tong; Yang, Jianping; Chen, Li-Hua

2018-02-19

Chronic itch is a distressing symptom of many skin diseases and negatively impacts quality of life. However, there is no medication for most forms of chronic itch, although antihistamines are often used for anti-itch treatment. Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, exhibits anti-oxidative and anti-inflammatory properties. Our previous studies highlighted a key role of oxidative stress and proinflammatory cytokines in acute and chronic itch. Here, we evaluated the effects of green tea polyphenon 60 and EGCG on acute and chronic itch in mouse models and explored its potential mechanisms. The effects of EGCG were determined by behavioral tests in mouse models of acute and chronic itch, which were induced by compound 48/80, chloroquine (CQ), and 5% imiquimod cream treatment, respectively. We found that systemic or local administration of green tea polyphenon 60 or EGCG significantly alleviated compound 48/80- and chloroquine-induced acute itch in a dose-dependent manner in mice. Incubation of EGCG significantly decreased the accumulation of intracellular reactive oxygen species (ROS) directly induced by compound 48/80 and CQ in cultured ND7-23 cells, a dorsal root ganglia derived cell line. EGCG also attenuated imiquimod-induced chronic psoriatic itch behaviors and skin epidermal hyperplasia in mice. In addition, EGCG inhibited the expression of IL-23 mRNA in skin and TRPV1 mRNA in dorsal root ganglia (DRG). Finally, EGCG remarkably inhibited compound 48/80-induced phosphorylation of extracellular signal-regulated kinase (ERK) and imiquimod-induced p-AKT in the spinal cord of mice, respectively. Collectively, these results indicated EGCG could be a promising strategy for anti-itch therapy. Copyright © 2018. Published by Elsevier Inc.

Resveratrol and Epigallocatechin-3-gallate addition to thawed boar sperm improves in vitro fertilization.

PubMed

Gadani, B; Bucci, D; Spinaci, M; Tamanini, C; Galeati, G

2017-03-01

Thawing is one of the most delicate process after semen cryopreservation as spermatozoa pass from a dormant metabolic stage to a sudden awakening in cellular metabolism. The rapid oxygen utilization leads to an overproduction of reactive oxygen species that can damage sperm cells, thus causing a significant decrease of fertilizing potential of frozen-thawed spermatozoa. Resveratrol (Res) is a natural grape-derived phytoalexin and Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea (Camellia sinensis); both molecules are known to possess high levels of antioxidant activity. The objective of the present study was to assess the effect of different concentrations of Res (0.5, 1 or 2 mM; Experiment 1) or EGCG (25, 50 or 100 μM; Experiment 2) supplementation to thawing boar semen extender on sperm quality parameters (viability and acrosome integrity) and in vitro fertilization (IVF). Semen after thawing and dilution with three volumes of Beltsville Thawing Solution (BTS), was immediately divided in control group without antioxidants addition (CTR) and either Res or EGCG groups. Sperm viability and acrosome integrity were evaluated in CTR, Res or EGCG groups after 1 h of incubation at 37 °C. The addition of different doses of Res or EGCG to thawing extender for 1 h did not induce any effect on boar sperm viability and acrosome integrity. However, both Res and EGCG treated samples exhibited a significantly higher penetration rate compared with CTR when used for IVF. In particular the treatment with all the EGCG concentrations increased the penetration rate (P < 0.01) while only Res 2 mM induced a significant increase of this parameter (P < 0.01). In addition, EGCG 25 and 50 μM supplementation significantly increased total fertilization efficiency as compared to control (EGCG 25 μM: 40.3 ± 8.2 vs 26.8 ± 9.5, P < 0.05; EGCG 50 μM: 40.4 ± 7.8 vs 26.8 ± 9.5, P < 0.01). The same effect was observed with Res 2 mM (51.0�

Epigallocatechin-3-Gallate Prevents Autoimmune-Associated Down-Regulation of p21 in Salivary Gland Cells Through a p53-Independent Pathway

PubMed Central

Dickinson, Douglas; Yu, Hongfang; Ohno, Seiji; Thomas, Cristina; DeRossi, Scott; Ma, Yat-Ho; Yates, Nicole; Hahn, Emily; Bisch, Frederick; Yamamoto, Tetsuya; Hsu, Stephen

2015-01-01

The submandibular salivary glands of non-obese diabetic (NOD) mice, a model for Sjogren’s syndrome and type-1 diabetes, show an elevated level of proliferating cell nuclear antigen (PCNA), a protein involved in cell proliferation and repair of DNA damage. We reported previously that epigallocatechin-3-gallate (EGCG), the most abundant green tea catechin, normalizes the PCNA level. PCNA’s activity can be regulated by the cyclin-dependent kinase inhibitor p21, which is also important for epithelial cell differentiation. In turn, expression of p21 and PCNA are partially regulated by Rb phosphorylation levels. EGCG was found to modulate p21 expression in epithelial cells, suggesting that EGCG-induced p21 could be associated with down-regulation of PCNA in vivo. The current study examined the protein levels of p21 and p53 (which can up-regulate p21) in NOD mice fed with either water or EGCG, and the effect of EGCG on p21 and p53 in cell line models with either normal or defective Rb. In NOD mice, the p21 level was low, and EGCG normalized it. In contrast to HSG cells with functional Rb, negligible expression of p21 in NS-SV-AC cells that lack Rb was not altered by EGCG treatment. Inhibition of p53 by siRNA demonstrated that p21 and p53 were induced independently in HSG cells by a physiological concentration range of EGCG, suggesting p53 could be an important but not conditional factor associated with p21 expression. In conclusion, PCNA and p21 levels are altered inversely in the NOD model for SS and in HSG cells, and warrant further study as candidate new markers for salivary dysfunction associated with xerostomia. Induction of p21 by EGCG could provide clinically useful normalization of salivary glands by promoting differentiation and reducing PCNA levels. PMID:24329914

Epigallocatechin gallate enhances treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia: A double-blind, randomized and placebo-controlled clinical study.

PubMed

Shi, D-D; Guo, J-J; Zhou, L; Wang, N

2018-02-01

Oral nifedipine is commonly used to treat pre-eclampsia, one of the most severe complications during pregnancy, but its clinical efficacy is less than ideal. Epigallocatechin gallate (EGCG), a natural compound from green tea, could benefit cardiovascular health especially hypertension. We investigated the clinical efficacy of EGCG, when complemented with oral nifedipine, in treating pre-eclampsia. A total of 350 pregnant women with severe pre-eclampsia were recruited and randomized to receive oral nifedipine, together with placebo (NIF+placebo) or EGCG (NIF+EGCG). The primary treatment outcome was the time needed to control blood pressure and interval time before a new hypertensive crisis, whereas the secondary treatment outcome was the number of treatment doses to effectively control blood pressure, maternal adverse effects and neonatal complications. Comparing NIF+EGCG group to NIF+placebo group, the time needed to control blood pressure was significantly shorter (NIF+EGCG 31.2±16.7 minutes, NIF+placebo 45.3±21.9 minutes; 95% CI 9.7-18.5 minutes), whereas interval time before a new hypertensive crisis was significantly prolonged (NIF+EGCG 7.2±2.9 hours, NIF+placebo 4.1±3.7 hours; 95% CI 2.3-3.9 hours), and the number of treatment dosages needed to effectively control blood pressure was also lower. Between the two treatment groups, no differences in incidence rates of maternal adverse effects or neonatal complications were observed. EGCG is both safe and effective in enhancing treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia, but formal validation is required prior to its recommendation for use outside of clinical trials. © 2017 John Wiley & Sons Ltd.

The effects of N-acetylcysteine and epigallocatechin-3-gallate on liver tissue protein oxidation and antioxidant enzyme levels after the exposure to radiofrequency radiation.

PubMed

Ozgur, Elcin; Sahin, Duygu; Tomruk, Arin; Guler, Goknur; Sepici Dinçel, Aylin; Altan, Nilgun; Seyhan, Nesrin

2015-02-01

The widespread and sustained use of mobile and cordless phones causes unprecedented increase of radiofrequency radiation (RFR). The aim of this experimental study was to investigate the effect of 900 MHz Global System for Mobile Communications (GSM)-modulated RFR (average whole body Specific Absorption Rate (SAR) of 0.4 W/kg, 10 or 20 min daily for consecutive 7 days) to the liver tissue of guinea pigs and the protective effects of antioxidant treatments. Adult male guinea pigs were randomly divided into nine groups as: Group I (sham/saline), Group II (sham/EGCG), Group III (sham/NAC), Group IV (10-min RF-exposure/saline), Group V (20-min RF-exposure/saline), Group VI (10-min RF-exposure/EGCG), Group VII (20-min RF-exposure/EGCG), Group VIII (10-min RF-exposure/NAC), and Group IX (20-min RF-exposure/NAC). Protein oxidation (PCO), advanced oxidation protein products (AOPP) and antioxidant enzyme activities of superoxide dismutase (SOD) were evaluated after the exposure and the treatments with N-acetylcysteine (NAC) and (-)-epigallocatechin-3-gallate (EGCG). Significant decreases in the activities of SOD were observed in the liver of guinea pigs after RFR exposure. Protein damage did not change due to RFR exposure. On the other hand, only NAC treatment induced increased PCO levels, whereas EGCG treatment alone elevated the level of AOPP. Due to antioxidants having pro-oxidant behavior, the well decided doses and treatment timetables of NAC and ECGC are needed.

The Green Tea Component (-)-Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity

PubMed Central

Lee, Hyeon-Ju; Byun, Catherine Jeonghae; Park, Jung-Hyun; Park, Jae Hoon; Cho, Ho-Seong; Cho, Sung-Jin; Jo, Sangmee Ahn; Jo, Inho

2015-01-01

The green tea component (-)-epigallocatechin-3-gallate (EGCG) has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As) or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC) at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose) polymerase (PARP), activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As) treatment significantly induced production of reactive oxygen species (ROS), which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK), which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity. PMID:26375285

The Green Tea Component (-)-Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

PubMed

Kim, Jee-Youn; Choi, Ji-Young; Lee, Hyeon-Ju; Byun, Catherine Jeonghae; Park, Jung-Hyun; Park, Jae Hoon; Cho, Ho-Seong; Cho, Sung-Jin; Jo, Sangmee Ahn; Jo, Inho

2015-01-01

The green tea component (-)-epigallocatechin-3-gallate (EGCG) has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As) or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC) at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose) polymerase (PARP), activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As) treatment significantly induced production of reactive oxygen species (ROS), which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK), which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

Polyphenols and Prostate Cancer Chemoprevention

DTIC Science & Technology

2005-03-01

ABSTRACT (Maximum 200 Words) The goal of this research is to Investigate the potential of (-)- epigallocatechin -3- gallate ( EGCG ), genistein and resveratrol...prostate chemoprevention are the soy isoflavone, genistein, and the tea catechin, (-)- epigallocatechin -3- gallate ( EGCG ). Another polyphenol that has...adenocarcinoma (TRAMP)). The specific aims are 1) to investigate the potential of genistein, EGCG and resveratrol, alone and in combination, to

Integrated Bioenvironmental Hazards Research Program

DTIC Science & Technology

2004-01-01

Elliott S, ZhaoW, Curiel TJ, Beckman BS, Burow ME. Epigallocatechin gallate ( EGCG ) induces growth inhibition and apoptosis in human breast cancer...Zhao DY, Elliott S, ZhaoW, Curiel TJ, Beckman BS, Burow ME. " Epigallocatechin gallate ( EGCG ) induces growth inhibition and apoptosis in human breast

Epigallocatechin gallate promotes the development of mouse 2-cell embryos in vitro by regulating mitochondrial activity and expression of genes related to p53 signalling pathway.

PubMed

Zhang, Weiyu; Lv, Junjie; Zhang, Yanqin; Jiang, Yufei; Chu, Chenfeng; Wang, Shie

2014-11-01

Preliminary studies have found that the epigallocatechin gallate (EGCG) at proper concentration could promote development of pre-implantation mouse embryos in vitro. However, the underlying mechanisms have not been well understood. In this study, we collected 1-cell embryos from Kunming (KM) mice, cultured them in M16 medium or M16 medium supplemented with 10 μg/mL EGCG and investigated the effects of EGCG on mitochondrial activity and reactive oxygen species (ROS) level of 2-cell embryos. Furthermore, we explored expression differences of genes related to p53 signalling pathway in 2-cell embryos using a PCR array. The results showed that ROS level and mitochondrial membrane potential were significantly lower in embryos cultured in the EGCG group than in the M16 group (p < 0.05), while the adenosine triphosphate content was slightly lower than in the M16 group (p > 0.05). PCR array test results showed that 18 genes were differentially expressed, among which eight genes involving cell growth, cell cycle regulation and mRNA transcription were up-regulated and 10 genes involving apoptosis, cell cycle arrest and DNA repair were down-regulated in the EGCG groups. It is concluded that EGCG could promote the development of 1-cell embryos in vitro possibly due to its ability to scavenge ROS and regulate mitochondrial activity. In addition, EGCG could influence expression of genes related to p53 signalling pathway in 2-cell embryos and promote cell cycle progression. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Development and evaluation of resveratrol, Vitamin E, and epigallocatechin gallate loaded lipid nanoparticles for skin care applications.

PubMed

Chen, Jin; Wei, Ning; Lopez-Garcia, Maria; Ambrose, Dianna; Lee, Jason; Annelin, Colin; Peterson, Teresa

2017-08-01

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24h. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic Effect of Artificial Tears Containing Epigallocatechin Gallate and Hyaluronic Acid for the Treatment of Rabbits with Dry Eye Syndrome.

PubMed

Tseng, Ching-Li; Hung, Ya-Jung; Chen, Zhi-Yu; Fang, Hsu-Wei; Chen, Ko-Hua

2016-01-01

Dry eye syndrome (DES) is a common eye disease. Artificial tears (AT) are used to treat DES, but they are not effective. In this study, we assessed the anti-inflammatory effect of AT containing epigallocatechin gallate (EGCG) and hyaluronic acid (HA) on DES. Human corneal epithelial cells (HCECs) were used in the WST-8 assay to determine the safe dose of EGCG. Lipopolysaccharide-stimulated HCECs showing inflammation were treated with EGCG/HA. The expression of IL-1ß, IL-6, IL-8, and TNF-α was assessed by real-time PCR and AT physical properties such as the viscosity, osmolarity, and pH were examined. AT containing EGCG and HA were topically administered in a rabbit DES model established by treatment with 0.1% benzalkonium chloride (BAC). Tear secretion was assessed and fluorescein, H&E, and TUNEL staining were performed. Inflammatory cytokine levels in the corneas were also examined. The non-toxic optimal concentration of EGCG used for the treatment of HCECs in vitro was 10 μg/mL. The expression of several inflammatory genes, including IL-1ß, IL-6, IL-8, and TNF-α, was significantly inhibited in inflamed HCECs treated with 10 μg/mL EGCG and 0.1% (w/v) HA (E10/HA) compared to that in inflamed HCECs treated with either EGCG or HA alone. AT containing E10/HA mimic human tears, with similar osmolarity and viscosity and a neutral pH. Fluorescence examination of the ocular surface of mouse eyes showed that HA increased drug retention on the ocular surface. Topical treatment of DES rabbits with AT plus E10/HA increased tear secretion, reduced corneal epithelial damage, and maintained the epithelial layers and stromal structure. Moreover, the corneas of the E10/HA-treated rabbits showed fewer apoptotic cells, lower inflammation, and decreased IL-6, IL-8, and TNF-α levels. In conclusion, we showed that AT plus E10/HA had anti-inflammatory and mucoadhesive properties when used as topical eye drops and were effective for treating DES in rabbits.

Down-Regulation of Myeloid Cell Leukemia 1 by Epigallocatechin-3-Gallate Sensitizes Rheumatoid Arthritis Synovial Fibroblasts to Tumor Necrosis Factor α–Induced Apoptosis

PubMed Central

Ahmed, Salahuddin; Silverman, Matthew D.; Marotte, Hubert; Kwan, Kevin; Matuszczak, Natalie; Koch, Alisa E.

2010-01-01

Objective Overexpression of the antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) in rheumatoid arthritis (RA) synovial fibroblasts is a major cause of their resistance to tumor necrosis factor α (TNFα)–induced apoptosis. This study was undertaken to evaluate the efficacy of epigallocatechin-3-gallate (EGCG) in down-regulating Mcl-1 expression and its mechanism of RA synovial fibroblast sensitization to TNFα-induced apoptosis. Methods EGCG effects on cultured RA synovial fibroblast cell morphology, proliferation, and viability over 72 hours were determined by microscopy and a fluorescent cell enumeration assay. Caspase 3 activity was determined by a colorimetric assay. Western blotting was used to evaluate the apoptosis mediators poly(ADP-ribose) polymerase (PARP), Mcl-1, Bcl-2, Akt, and nuclear translocation of NF-κB. Results In RA synovial fibroblasts, EGCG (5–50 μM) inhibited constitutive and TNFα-induced Mcl-1 protein expression in a concentration- and time-dependent manner (P < 0.05). Importantly, EGCG specifically abrogated Mcl-1 expression in RA synovial fibroblasts and affected Mcl-1 expression to a lesser extent in osteoarthritis and normal synovial fibroblasts or endothelial cells. Inhibition of Mcl-1 by EGCG triggered caspase 3 activity in RA synovial fibroblasts, which was mediated via down-regulation of the TNFα-induced Akt and NF-κB pathways. Caspase 3 activation by EGCG also suppressed RA synovial fibroblast growth, and this effect was mimicked by Akt and NF-κB inhibitors. Interestingly, Mcl-1 degradation by EGCG sensitized RA synovial fibroblasts to TNFα-induced PARP cleavage and apoptotic cell death. Conclusion Our findings indicate that EGCG itself induces apoptosis and further sensitizes RA synovial fibroblasts to TNFα-induced apoptosis by specifically blocking Mcl-1 expression and, hence, may be of promising adjunct therapeutic value in regulating the invasive growth of synovial fibroblasts in RA. PMID:19404960

Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores.

PubMed

Kim, Hee Jung; Yum, Keun Sang; Sung, Jong-Ho; Rhie, Duck-Joo; Kim, Myung-Jun; Min, Do Sik; Hahn, Sang June; Kim, Myung-Suk; Jo, Yang-Hyeok; Yoon, Shin Hee

2004-02-01

Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 micro M) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 micro M) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 micro M) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 micro M) and flufenamic acid (100 micro M), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 micro M) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.

Epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor and effectively alleviates acute lung injury induced by H9N2 swine influenza virus.

PubMed

Xu, Ming-Ju; Liu, Bao-Jian; Wang, Cun-Lian; Wang, Guo-Hua; Tian, Yong; Wang, Shao-Hua; Li, Jun; Li, Pei-Yao; Zhang, Rui-Hua; Wei, Dong; Tian, Shu-Fei; Xu, Tong

2017-11-01

Epigallocatechin-3-gallate (EGCG) was found to inhibit the Toll-like receptor 4 (TLR4) pathway involved in influenza virus pathogenesis. Here, the effect of EGCG on TLR4 in an H9N2 virus-induced acute lung injury mouse model was investigated. BALB/c mice were inoculated intranasally with A/Swine/Hebei/108/2002 (H9N2) virus or noninfectious allantoic fluid, and treated with EGCG and E5564 or normal saline orally for 5 consecutive days. PMVECs were treated with EGCG or anti-67kDa laminin receptor (LR). Lung physiopathology, inflammation, oxidative stress, viral replication, and TLR4/NF-κB/Toll-interacting protein (Tollip) pathway in lung tissue and/or PMVECs were investigated. EGCG attenuated lung histological lesions, decreased lung W/D ratio, cytokines levels, and inhibited MPO activity and prolonged mouse survival. EGCG treatment also markedly downregulated TLR4 and NF-κB protein levels but Tollip expression was upregulated compared with that in untreated H9N2-infected mice (P<0.05). In PMVECs, anti-67LR antibody treatment significantly downregulated Tollip levels; however, the TLR4 and NF-κB protein levels dramatically increased compared with that in the EGCG-treated group (P<0.05). EGCG remarkably downregulated TLR4 protein levels through 67LR/Tollip, decreased MPO activity and inflammatory cytokine levels, supporting EGCG as a potential therapeutic agent for managing acute lung injury induced by H9N2 SIV. Copyright © 2017 Elsevier B.V. All rights reserved.

Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice.

PubMed

Dong, Ruixia; Wang, Dongxu; Wang, Xiaoxiao; Zhang, Ke; Chen, Pingping; Yang, Chung S; Zhang, Jinsong

2016-12-01

Selenium participates in the antioxidant defense mainly through a class of selenoproteins, including thioredoxin reductase. Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechin in green tea. Depending upon the dose and biological systems, EGCG may function either as an antioxidant or as an inducer of antioxidant defense via its pro-oxidant action or other unidentified mechanisms. By manipulating the selenium status, the present study investigated the interactions of EGCG with antioxidant defense systems including the thioredoxin system comprising of thioredoxin and thioredoxin reductase, the glutathione system comprising of glutathione and glutathione reductase coupled with glutaredoxin, and the Nrf2 system. In selenium-optimal mice, EGCG increased hepatic activities of thioredoxin reductase, glutathione reductase and glutaredoxin. These effects of EGCG appeared to be not due to overt pro-oxidant action because melatonin, a powerful antioxidant, did not influence the increase. However, in selenium-deficient mice, with low basal levels of thioredoxin reductase 1, the same dose of EGCG did not elevate the above-mentioned enzymes; intriguingly EGCG in turn activated hepatic Nrf2 response, leading to increased heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 protein levels and thioredoxin activity. Overall, the present work reveals that EGCG is a robust inducer of the Nrf2 system only in selenium-deficient conditions. Under normal physiological conditions, in selenium-optimal mice, thioredoxin and glutathione systems serve as the first line defense systems against the stress induced by high doses of EGCG, sparing the activation of the Nrf2 system. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Preventive Role of Specific Dietary Factors and Natural Compounds Against DNA Damage and Oxidative Stress.

DTIC Science & Technology

1998-08-01

vitamins (C and E) and natural compounds (caffeic acid phenethyl ester [CAPE] and epigallocatechin gallate [ EGCG ] may be protective against mammary...caffeic acid phenethyl ester (CAPE), and epigallocatechin gallate ( EGCG ) in inhibiting DNA damage. These antioxidants are found in natural products such...as fruits and vegetables (vitamins C and E), the popular medicine honeybee propolis (CAPE), or green tea ( EGCG ). Studies carried out to date suggest

Punicalagin and (-)-Epigallocatechin-3-Gallate Rescue Cell Viability and Attenuate Inflammatory Responses of Human Epidermal Keratinocytes Exposed to Airborne Particulate Matter PM10.

PubMed

Seok, Jin Kyung; Lee, Jeong-Won; Kim, Young Mi; Boo, Yong Chool

2018-01-01

Airborne particulate matter with a diameter of < 10 µm (PM10) causes oxidative damage, inflammation, and premature skin aging. In this study, we evaluated whether polyphenolic antioxidants attenuate the inflammatory responses of PM10-exposed keratinocytes. Primary human epidermal keratinocytes were exposed in vitro to PM10 in the absence or presence of punicalagin and (-)-epigallocatechin-3-gallate (EGCG), which are the major polyphenolic antioxidants found in pomegranate and green tea, respectively. Assays were performed to determine cell viability, production of reactive oxygen species (ROS), and expression of NADPH oxidases (NOX), proinflammatory cytokines, and matrix metalloproteinase (MMP)-1. PM10 decreased cell viability and increased ROS production in a dose-dependent manner. It also increased the expression levels of NOX-1, NOX-2, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, and MMP-1. Punicalagin was not cytotoxic up to 300 μM, and (-)-EGCG was cytotoxic above 30 μM, respectively. Further, punicalagin (3-30 μM) and EGCG (3-10 μM) rescued the viability of PM10-exposed cells. They also attenuated ROS production and the expression of NOX-1, NOX-2, TNF-α, IL-1β, IL-6, IL-8, and MMP-1 stimulated by PM10. This study demonstrates that polyphenolic antioxidants, such as punicalagin and (-)-EGCG, rescue keratinocyte viability and attenuate the inflammatory responses of these cells due to airborne particles. © 2018 S. Karger AG, Basel.

(-)-Epigallocatechin-3-Gallate Modulates Spinal Cord Neuronal Degeneration by Enhancing Growth-Associated Protein 43, B-Cell Lymphoma 2, and Decreasing B-Cell Lymphoma 2-Associated X Protein Expression after Sciatic Nerve Crush Injury

PubMed Central

Al-Maghrebi, May; Rao, Muddanna S.; Khraishah, Haitham

2015-01-01

Abstract Our previous studies have established that (-)-epigallocatechin-3-gallate (EGCG) has both neuroprotective and -regenerative capacity after sciatic nerve injury. Moreover, this improvement was evident on the behavioral level. The aim of this study was to investigate the central effects of ECGC on spinal cord motor neurons after sciatic nerve injury. Our study showed that administering 50 mg/kg intraperitoneally i.p. of EGCG to sciatic nerve-injured rats improved their performance on different motor functions and mechanical hyperesthesia neurobehavioral tests. Histological analysis of spinal cords of EGCG-treated sciatic nerve-injured (CRUSH+ECGC) animals showed an increase in the number of neurons in the anterior horn, when compared to the naïve, sham, and saline-treated sciatic nerve-injured (CRUSH) control groups. Additionally, immunohistochemical study of spinal cord sections revealed that EGCG reduced the expression of glial fibrillary acidic protein and increased the expression of growth-associated protein 43, a marker of regenerating axons. Finally, EGCG reduced the ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 and increased the expression of survivin gene. This study may shed some light on the future clinical use of EGCG and its constituents in the treatment of peripheral nerve injury. PMID:25025489

"Stealth and Fully-Laden" Drug Carriers: Self-Assembled Nanogels Encapsulated with Epigallocatechin Gallate and siRNA for Drug-Resistant Breast Cancer Therapy.

PubMed

Ding, Jie; Liang, Tingxizi; Min, Qianhao; Jiang, Liping; Zhu, Jun-Jie

2018-03-28

For codelivery of therapeutic genes and chemical agents in combined therapy, the ideal drug delivery system entails high-capacity and low-body toxicity carriers, allowing adequate drug dose for tumor regions while yielding low residues in normal tissues. To augment the gene/drug load capacity and circumvent the potential toxicity brought by traditional inorganic and polymeric nanocarriers, a "stealth" carrier was herein designed in a simple self-assembly of (-)-epigallocatechin-3- O-gallate (EGCG) and small interfering RNA (siRNA) by recruiting protamine as a biodegradable medium for the treatment of drug-resistant triple-negative breast cancer. In the self-assembled nanogel, entrapped siRNA played a central role in sensitizing the tumor response to EGCG-involved chemotherapy, and the positively charged protamine served as the assembly skeleton to fully accommodate gene and drug molecules and minimize the factors causing side effects. As compared to stand-alone chemotherapy with EGCG, the multicomponent nanogel revealed a 15-fold increase in the cytotoxicity to drug-resistant MDA-MB-231 cell line. Moreover, equipped with hyaluronic acid and tumor-homing cell-penetrating peptide as the outmost targeting ligands, the siRNA- and EGCG-loaded nanogel demonstrates superior selectivity and tumor growth inhibition to free EGCG in xenograft MDA-MB-231 tumor-bearing mice. Meanwhile, thanks to the acknowledged biosafety of protamine, little toxicity was found to normal tissues and organs in the animal model. This gene/drug self-assembly caged in a biodegradable carrier opens up an effective and secure route for drug-resistant cancer therapy and provides a versatile approach for codelivery of other genes and drugs for different medical purposes.

New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate☆

PubMed Central

Kim, Hae-Suk; Quon, Michael J.; Kim, Jeong-a

2014-01-01

Green tea is rich in polyphenol flavonoids including catechins. Epigallocatechin 3-gallate (EGCG) is the most abundant and potent green tea catechin. EGCG has been extensively studied for its beneficial health effects as a nutriceutical agent. Based upon its chemical structure, EGCG is often classified as an antioxidant. However, treatment of cells with EGCG results in production of hydrogen peroxide and hydroxyl radicals in the presence of Fe (III). Thus, EGCG functions as a pro-oxidant in some cellular contexts. Recent investigations have revealed many other direct actions of EGCG that are independent from anti-oxidative mechanisms. In this review, we discuss these novel molecular mechanisms of action for EGCG. In particular, EGCG directly interacts with proteins and phospholipids in the plasma membrane and regulates signal transduction pathways, transcription factors, DNA methylation, mitochondrial function, and autophagy to exert many of its beneficial biological actions. PMID:24494192

The Effect of (-)-Epigallocatechin 3-O - Gallate In Vitro and In Vivo in Leishmania braziliensis: Involvement of Reactive Oxygen Species as a Mechanism of Action

PubMed Central

Inacio, Job D. F.; Gervazoni, Luiza; Canto-Cavalheiro, Marilene M.; Almeida-Amaral, Elmo E.

2014-01-01

Background Leishmaniasis is a parasitic disease associated with extensive mortality and morbidity. The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. Natural compounds have been used as novel treatments for parasitic diseases. In this paper, we evaluated the effect of (-)-epigallocatechin 3-O-gallate (EGCG) on Leishmania braziliensis in vitro and in vivo and described the mechanism of EGCG action against L. braziliensis promastigotes and intracellular amastigotes. Methodology/Principal Finding In vitro activity and reactive oxygen species (ROS) measurements were determined during the promastigote and intracellular amastigote life stages. The effect of EGCG on mitochondrial membrane potential (ΔΨm) was assayed using JC-1, and intracellular ATP concentrations were measured using a luciferin-luciferase system. The in vivo experiments were performed in infected BALB/c mice orally treated with EGCG. EGCG reduced promastigote viability and the infection index in a time- and dose-dependent manner, with IC50 values of 278.8 µM and 3.4 µM, respectively, at 72 h and a selectivity index of 149.5. In addition, EGCG induced ROS production in the promastigote and intracellular amastigote, and the effects were reversed by polyethylene glycol (PEG)-catalase. Additionally, EGCG reduced ΔΨm, thereby decreasing intracellular ATP concentrations in promastigotes. Furthermore, EGCG treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. Conclusions/Significance In conclusion, our study demonstrates the leishmanicidal effects of EGCG against the two forms of L. braziliensis, the promastigote and amastigote. In addition, EGCG promotes ROS production as a part of its mechanism of action, resulting in decreased ΔΨm and reduced intracellular ATP concentrations. These actions ultimately

Laminin Receptor-Avid Nanotherapeutic EGCg-AuNPs as a Potential Alternative Therapeutic Approach to Prevent Restenosis

PubMed Central

Khoobchandani, Menka; Katti, Kavita; Maxwell, Adam; Fay, William P.; Katti, Kattesh V.

2016-01-01

In our efforts to develop new approaches to treat and prevent human vascular diseases, we report herein our results on the proliferation and migration of human smooth muscles cells (SMCs) and endothelial cells (ECs) using epigallocatechin-3-gallate conjugated gold nanoparticles (EGCg-AuNPs) as possible alternatives to drug coated stents. Detailed in vitro stability studies of EGCg-AuNPs in various biological fluids, affinity and selectivity towards SMCs and ECs have been investigated. The EGCg-AuNPs showed selective inhibitory efficacy toward the migration of SMCs. However, the endothelial cells remained unaffected under similar experimental conditions. The cellular internalization studies have indicated that EGCg-AuNPs internalize into the SMCs and ECs within short periods of time through laminin receptor mediated endocytosis mode. Favorable toxicity profiles and selective affinity toward SMCs and ECs suggest that EGCg-AuNPs may provide attractive alternatives to drug coated stents and therefore offer new therapeutic approaches in treating cardiovascular diseases. PMID:26938531

Synthesis and Structure activity relationships of EGCG Analogues, A Recently Identified Hsp90 Inhibitor

PubMed Central

Khandelwal, Anuj; Hall, Jessica

2014-01-01

Epigallocatechin-3-gallate (EGCG), the principal polyphenol isolated from green tea, was recently shown to inhibit Hsp90, however structure-activity relationships for this natural product have not yet been produced. Herein, we report the synthesis and biological evaluation of EGCG analogues to establish structure-activity relationships between EGCG and Hsp90. All four rings as well as the linker connecting the C- and the D-rings were systematically investigated, which led to the discovery of compounds that inhibit Hs90 and display improvement in efficacy over EGCG. Anti-proliferative activity of all the analogues was determined against MCF-7 and SKBr3 cell lines and Hsp90 inhibitory activity of four most potent analogues was further evaluated by western blot analyses and degradation of Hsp90-dependent client proteins. Prenyl substituted aryl ester of 3,5-dihydroxychroman-3-ol ring system was identified as novel scaffold that exhibit Hsp90 inhibitory activity. PMID:23834230

Oxygen partial pressure modulates 67-kDa laminin receptor expression, leading to altered activity of the green tea polyphenol, EGCG.

PubMed

Tsukamoto, Shuntaro; Yamashita, Shuya; Kim, Yoon Hee; Kumazoe, Motofumi; Huang, Yuhui; Yamada, Koji; Tachibana, Hirofumi

2012-09-21

(-)-Epigallocatechin-3-O-gallate (EGCG) exhibits anti-tumor activity mediated via the 67-kDa laminin receptor (67LR). In this study, we found that 67LR protein levels are reduced by exposure to low O(2) levels (5%), without affecting the expression of HIF-1α. We also found that EGCG-induced anti-cancer activity is abrogated under low O(2) levels (5%) in various cancer cells. Notably, treatment with the proteasome inhibitor, prevented down-regulation of 67LR and restored sensitivity to EGCG under 5% O(2). In summary, 67LR expression is highly sensitive to O(2) partial pressure, and the activity of EGCG can be regulated in cancer cells by O(2) partial pressure. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

In vitro and in vivo inhibition of aldose reductase and advanced glycation end products by phloretin, epigallocatechin 3-gallate and [6]-gingerol.

PubMed

Sampath, Chethan; Sang, Shengmin; Ahmedna, Mohamed

2016-12-01

Hyperglycemic stress activates polyol pathway and aldose reductase (AR) key enzyme responsible for generating secondary complications during diabetes. In this study the therapeutic potential of phloretin, epigallocatechin 3-gallate (EGCG) and [6]-gingerol were evaluated for anti-glycating and AR inhibitory activity in vitro and in vivo systems. Human retinal pigment epithelial (HRPE) cells were induced with high glucose supplemented with the phloretin, EGCG and [6]-gingerol. Aldose reductase activity, total advanced glycation end products (AGEs) and enzyme inhibitor kinetics were assessed. Male C57BL/6J mice were randomly assigned to one of the different treatments (bioactive compounds at 2 concentrations each) with either a low fat diet or high fat diet (HFD). After sixteen weeks, AGE accumulation and AR activity was determined in heart, eyes and kidney. High glucose induced toxicity decreased cell viability compared to the untreated cells and AR activity increased to 2-5 folds from 24 to 96h. Pre-treatment of cells with phloretin, EGCG and [6]-gingerol improved cell viability and inhibited AR activity. The enzyme inhibition kinetics followed a non-competitive mode of inhibition for phloretin and EGCG whereas [6]-gingerol indicated uncompetitive type of inhibition against AR. Data from the animal studies showed high plasma glucose levels in HFD group over time, compared to the low fat diet. HFD group developed cataract and AR activity increased to 4 folds compared to the group with low fat diet. Administration of EGCG, phloretin and [6]-gingerol significantly reduced blood sugar levels, AGEs accumulation, and AR activity. These findings could provide a basis to consider using the selected dietary components alone or in combination with other therapeutic approaches to prevent diabetes-related complications in humans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Determination of exogenous epigallocatechin gallate peracetate in mouse plasma using liquid chromatography with quadrupole time-of-flight mass spectrometry.

PubMed

Chu, Kai On; Man, Gene Chi Wai; Chan, Kwok Ping; Chu, Ching Yan; Chan, Tak Hang; Pang, Chi Pui; Wang, Chi Chiu

2014-12-01

A robust method for the quantitation of epigallocatechin gallate peracetate in plasma for pharmacokinetic studies is lacking. We have developed a validated method to quantify this compound using liquid chromatography with quadrupole time-of-flight mass spectrometry with isopropanol and tert-butyl methyl ether (3:10) extraction and thin-layer chromatography purification. The epigallocatechin gallate peracetate-1-(13) C8 isotope was used as an internal standard. The linear range (r(2) > 0.9950) was from 0.05 to 100.00 μg/mL. The lower limit of quantification of the method was 0.05 μg/mL. Reproducibility, coefficient of variation, was between 0.7 and 12.6% (n = 6), accuracy between 83.7 and 104.6% (n = 5), and recovery ranged from 82.4 to 109.0% (n = 4). Ion suppression was approximately 40%. No mass spectral peaks were found to interfere between the standard and internal standard or the blank plasma extracts. Epigallocatechin gallate peracetate in plasma was stably stored at -80°C over three months even after three freeze-thaw cycles. Extracts were stable in the sampler at 4°C for over 48 h. Plasma levels were maintained at 1.36 μg/mL for 360 min after intraorbital intravenous injection at 50 mg/kg in mice. This method can be used to reliably measure epigallocatechin gallate peracetate in plasma for pharmacokinetic studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigation of epigallocatechin-3-O-caffeoate and epigallocatechin-3-O-p-coumaroate in tea leaves by LC/MS-MS analysis.

PubMed

Umehara, Masahiro; Yanae, Koji; Maruki-Uchida, Hiroko; Sai, Masahiko

2017-12-01

(-)-Epigallocatechin-3-O-gallate (EGCG), the major catechin present in green tea, exhibits potent antioxidant activity. We thereby investigated the presence of unknown components bearing the (-)-epigallocatechin (EGC) moiety in fresh tea leaf samples. Initially, liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to examine fresh tea leaves of the Yabukita, the most popular tea cultivar in Japan, which suggested the presence of the EGC phenylpropanoid derivatives, (-)-epigallocatechin-3-O-p-coumaroate (EGCpCA) and (-)-epigallocatechin-3-O-caffeoate (EGCCA). The structures of the detected EGCpCA and EGCCA were then confirmed by LC-MS/MS using synthesized EGCpCA and EGCCA as standards. In addition, EGCpCA and EGCCA were evaluated for their antioxidant activity in the ORAC (oxygen radical antioxidant capacity) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assays, where EGCCA (8.60μmolTE/μmol, TE=Trolox equivalents) exhibited a stronger antioxidant activity than EGCG (5.52μmolTE/μmol) in the ORAC assay. Finally, EGCpCA and EGCCA were quantitated in several tea leaf samples using LC-MS/MS, and it was found that these compounds were present in lower quantities (EGCpCA, 16.8-345.8μg/g, EGCCA, 4.3-75.1μg/g in the dry tea leaves) than the major catechins. In this study, we found the potent antioxidant EGCCA using LC-MS/MS and revealed its wide existence in various tea leaves. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tea polyphenol epigallocatechin 3-gallate impedes the anti-apoptotic effects of low-grade repetitive stress through inhibition of Akt and NFkappaB survival pathways.

PubMed

Sen, Prosenjit; Chakraborty, Prabir Kumar; Raha, Sanghamitra

2006-01-09

V79 Chinese Hamster lung fibroblasts were subjected to repetitive low-grade stress through multiple exposures to 30 microM H2O2 in culture for 4 weeks. Akt/protein kinase B became phosphorylated at serine473 and threonine308 during this period of repetitive stress. Concurrent exposure of the cells to LY294002 (5 microM), a phosphoinositide-3 kinase inhibitor or 4.5 microM epigallocatechin 3-gallate (EGCG), a tea polyphenol almost completely blocked Akt activation by repetitive stress. Phosphorylation of I kappa B kinase (IKK) and transcriptional activity driven by nuclear factor kappa B (NFkappaB) were significantly enhanced by repetitive oxidative stress. These increases were largely abolished by simultaneous exposure to EGCG. The repetitively stressed cells demonstrated a significant resistance to apoptosis by subsequent acute stress in the form of ultraviolet radiation at 5 J/m2 or H2O2 (7.5 mM). The resistance to apoptosis conferred by repetitive stress was drastically reduced (>80%) by constant exposure to EGCG during the stress period while the presence of LY294002 or the NFkappaB inhibitor SN50 brought about a relatively moderate effect (about 50-65%). Our data indicate that activation of Akt and NFkappaB pro-survival pathways by repetitive low-grade stress results in a strong inhibition of the normal apoptotic response after subsequent acute stress. The tea polyphenol EGCG impedes the activation of both Akt and NFkappaB by repetitive stress and as a result preserves the normal apoptotic response during subsequent acute stress.

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures.

PubMed

Baumeister, Philipp; Reiter, Maximilian; Kleinsasser, Norbert; Matthias, Christoph; Harréus, Ulrich

2009-06-01

Although epidemiological studies indicate cancer preventive effects of diets rich in fruit and vegetables, large clinical intervention studies conducted to evaluate dietary supplementation with micronutrients, mostly vitamins, showed disappointing results in large parts. In contrast, there is encouraging epidemiologic data indicating great chemopreventive potential of a large group of phytochemicals, namely polyphenols. This study shows the DNA protective effect epigallocatechin-3-gallate, a tea catechin, and one of the best-studied substances within this group, on carcinogen-induced DNA fragmentation in upper aerodigestive tract cells. Cell cultures from fresh oropharyngeal mucosa biopsies were preincubated with epigallocatechin-3-gallate in different concentrations before DNA damage was introduced with the metabolically activated carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide or cigarette smoke condensate. Effects on resulting DNA fragmentation were measured using the alkaline single-cell microgel electrophoresis (comet assay). Epigallocatechin-3-gallate significantly reduced benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage by up to 51% (P<0.001). Fragmentation induced by cigarette smoke condensate could be lowered by 47% (P<0.001). Data suggest a cancer preventive potential of epigallocatechin-3-gallate as demonstrated on a subcellular level. An additional mechanism of tea catechin action is revealed by using a primary mucosa culture model.

Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes.

PubMed

Rasheed, Zafar; Anbazhagan, Arivarasu N; Akhtar, Nahid; Ramamurthy, Sangeetha; Voss, Frank R; Haqqi, Tariq M

2009-01-01

The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age-related accumulation of advanced glycation end products (AGEs) can activate chondrocytes and induce the production of proinflammatory cytokines and matrix metalloproteinases (MMPs). In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG) on AGE-modified-BSA (AGE-BSA)-induced activation and production of TNFalpha and MMP-13 in human OA chondrocytes. Human chondrocytes were derived from OA cartilage by enzymatic digestion and stimulated with in vitro-generated AGE-BSA. Gene expression of TNFalpha and MMP-13 was measured by quantitative RT-PCR. TNFalpha protein in culture medium was determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the MMP-13 production in the culture medium, phosphorylation of mitogen-activated protein kinases (MAPKs), and the activation of NF-kappaB. DNA binding activity of NF-kappaB p65 was determined using a highly sensitive and specific ELISA. IkappaB kinase (IKK) activity was determined using an in vitro kinase activity assay. MMP-13 activity in the culture medium was assayed by gelatin zymography. EGCG significantly decreased AGE-stimulated gene expression and production of TNFalpha and MMP-13 in human chondrocytes. The inhibitory effect of EGCG on the AGE-BSA-induced expression of TNFalpha and MMP-13 was mediated at least in part via suppression of p38-MAPK and JNK activation. In addition, EGCG inhibited the phosphorylating activity of IKKbeta kinase in an in vitro activity assay and EGCG inhibited the AGE-mediated activation and DNA binding activity of NF-kappaB by suppressing the degradation of its inhibitory protein IkappaBalpha in the cytoplasm. These novel pharmacological actions of EGCG on AGE-BSA-stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG-derived compounds may inhibit cartilage degradation by suppressing AGE

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

PubMed

Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

2016-08-01

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.

Impact of the green tea ingredient epigallocatechin gallate and a short pentapeptide (Ile-Ile-ala-Glu-Lys) on the structural organization of mixed micelles and the related uptake of cholesterol.

PubMed

Giangreco, Francesco; Höfinger, Siegfried; Bakalis, Evangelos; Zerbetto, Francesco

2018-06-07

High levels of blood cholesterol are conventionally linked to an increased risk of developing cardiovascular disease (Grundy, 1986). Here we examine the molecular mode of action of natural products with known cholesterol-lowering activity, such as for example the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys. Molecular Dynamics simulations are used to gain insight into the formation process of mixed micelles and, correspondingly, how active agents epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys could possibly interfere with it. Self-assembly of physiological micelles occurs on the order of 35-50 ns; most of the structural properties of mixed micelles are unaffected by epigallocatechin gallate or Ile-Ile-Ala-Glu-Lys which integrate into the micellar surface; the diffusive motion of constituting lipids palmitoyl-oleoyl-phosphatidylcholine and cholesterol is significantly down-regulated by both epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys; CONCLUSIONS: The molecular mode of action of natural compounds epigallocatechin gallate and Ile-Ile-Ala-Glu-Lys is a significant down-regulation of the diffusive motion of micellar lipids. Natural compounds like the green tea ingredient epigallocatechin gallate and a short pentapeptide, Ile-Ile-Ala-Glu-Lys, lead to a significant down-regulation of the diffusive motion of micellar lipids thereby modulating cholesterol absorption into physiological micelles. Copyright © 2018. Published by Elsevier B.V.

Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice.

PubMed

Ding, Mei-Li; Ma, Hui; Man, Yi-Gang; Lv, Hong-Yan

2017-12-01

Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7. EGCG significantly inhibited sevoflurane-induced neuroapoptosis as determined by Fluoro-Jade B staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Increased levels of cleaved caspase-3, downregulated Bad and Bax, and significantly enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, and survivin expression were observed. EGCG induced activation of the PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3β, phospho-GSK-3β, and mTORc1 levels. Sevoflurane-mediated downregulation of cAMP/CREB and BDNF/TrkB signalling was inhibited by EGCG. Reverse transcription PCR analysis revealed enhanced BDNF and TrkB mRNA levels upon EGCG administration. Improved performance of mice in Morris water maze tests suggested enhanced learning and memory. The study indicates that EGCG was able to effectively inhibit sevoflurane-induced neurodegeneration and improve learning and memory retention of mice via activation of CREB/BDNF/TrkB-PI3K/Akt signalling.

Synergistic growth inhibition of squamous cell carcinoma of the head and neck by erlotinib and epigallocatechin-3-gallate: the role of p53-dependent inhibition of nuclear factor-kappaB.

PubMed

Amin, A R M Ruhul; Khuri, Fadlo R; Chen, Zhuo Georgia; Shin, Dong M

2009-06-01

We have previously reported that the green tea polyphenol epigallocatechin-3-gallate (EGCG) and the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib had synergistic growth-inhibitory effects in cell culture and a nude mouse xenograft model of squamous cell carcinoma of the head and neck. However, the mechanism of their antitumor synergism is not fully understood. In the current study, we investigate the mechanism of their synergistic growth-inhibitory effects. The treatment of squamous cell carcinoma of the head and neck cell lines with erlotinib time-dependently increased the expression of cell cycle regulatory proteins p21 and p27 and apoptosis regulatory protein Bim. EGCG alone had very little or no effect on the expression of these proteins among the cell lines. However, simultaneous treatment with EGCG and erlotinib strongly inhibited erlotinib-induced expression of p21 and p27 without affecting the expression of Bim. Moreover, erlotinib increased the expression of p53 protein, the ablation of which by short hairpin RNA strongly inhibited EGCG- and erlotinib-mediated growth inhibition and the expression of p21, p27, and Bim. In addition, combined treatment with erlotinib and EGCG inhibited the protein level of p65 subunit of nuclear factor-kappaB and its transcriptional target Bcl-2, but failed to do so in cells with ablated p53. Taken together, our results, for the first time, suggest that erlotinib treatment activates p53, which plays a critical role in synergistic growth inhibition by erlotinib and EGCG via inhibiting nuclear factor-kappaB signaling pathway. Characterizing the underlying mechanisms of EGCG and erlotinib synergism will provide an important rationale for chemoprevention or treatment trials using this combination.

Effects of green tea catechins on gramicidin channel function and inferred changes in bilayer properties

PubMed Central

Ingólfsson, Helgi I.; Koeppe, Roger E.; Andersen, Olaf S.

2011-01-01

Green tea's health benefits have been attributed to its major polyphenols, the catechins: (−)-epigallocatechin gallate (EGCG), (−)-epicatechin gallate (ECG), (−)-epigallocatechin (EGC), and epicatechin (EC). Catechins (especially EGCG) modulate a wide range of biologically important molecules, including many membrane proteins. Yet, little is known about their mechanism(s) of action. We tested the catechins' bilayer-modifying potency using gramicidin A (gA) channels as molecular force probes. All the catechins alter gA channel function and modify bilayer properties, with a 500-fold range in potency (EGCG > ECG >> EGC > EC). Additionally, the gallate group causes current block, as evident by brief downward current transitions (flickers). PMID:21896274

Monitoring and Counteracting Functional Deterioration in Parkinson’s Disease: A Multilevel Integrative Approach in a Primate Model System

DTIC Science & Technology

2007-09-01

1992; Fukuda, 2001). The effects of Riluzole (anti-excitotoxic) treatment, epigallocatechin -3- gallate ( EGCG ; anti-oxidative) treatment and (currently... gallate ( EGCG ) is a compound derived from green tea and is beneficial for a number of conditions like obesity and cardiovascular failure (Chantre and...O- gallate ( EGCG ; Teavigo®) was provided bij DSM, Switserland. The anti-excitotoxic compound Riluzole (Rilutek) was obtained at Wippolder Pharmacy

Short- and long-term effects of neonatal pharmacotherapy with epigallocatechin-3-gallate on hippocampal development in the Ts65Dn mouse model of Down syndrome.

PubMed

Stagni, Fiorenza; Giacomini, Andrea; Emili, Marco; Trazzi, Stefania; Guidi, Sandra; Sassi, Martina; Ciani, Elisabetta; Rimondini, Roberto; Bartesaghi, Renata

2016-10-01

Cognitive disability is an unavoidable feature of Down syndrome (DS), a genetic disorder due to the triplication of human chromosome 21. DS is associated with alterations of neurogenesis, neuron maturation and connectivity that are already present at prenatal life stages. Recent evidence shows that pharmacotherapies can have a large impact on the trisomic brain provided that they are administered perinatally. Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, performs many actions in the brain, including inhibition of DYRK1A, a kinase that is over-expressed in the DS brain and contributes to the DS phenotype. Young adults with DS treated with EGCG exhibit some cognitive benefits, although these effects disappear with time. We deemed it extremely important, however, to establish whether treatment with EGCG at the initial stages of brain development leads to plastic changes that outlast treatment cessation. In the current study, we exploited the Ts65Dn mouse model of DS in order to establish whether pharmacotherapy with EGCG during peak of neurogenesis in the hippocampal dentate gyrus (DG) enduringly restores hippocampal development and memory performance. Euploid and Ts65Dn mice were treated with EGCG from postnatal day 3 (P3) to P15. The effects of treatment were examined at its cessation (at P15) or after one month (at P45). We found that at P15 treated trisomic pups exhibited restoration of neurogenesis, total hippocampal granule cell number and levels of pre- and postsynaptic proteins in the DG, hippocampus and neocortex. However, at P45 none of these effects were still present, nor did treated Ts65Dn mice exhibit any improvement in hippocampus-dependent tasks. These findings show that treatment with EGCG carried out in the neonatal period rescues numerous trisomy-linked brain alterations. However, even during this, the most critical time window for hippocampal development, EGCG does not elicit enduring effects on the hippocampal physiology

Ferritin glycosylated by chitosan as a novel EGCG nano-carrier: Structure, stability, and absorption analysis.

PubMed

Yang, Rui; Liu, Yuqian; Gao, Yunjing; Wang, Yongjin; Blanchard, Chris; Zhou, Zhongkai

2017-12-01

Ferritin is a shell-like carrier protein with an 8nm diameter cavity which endows a natural space to encapsulate food and drug components. In this work, phytoferritin was unprecedentedly glycosylated by chitosan to fabricate ferritin-chitosan Maillard reaction products (FCMPs) (grafting degree of 26.17%, 24h, 55°C). Results indicated that the amide I and II bands of ferritin were altered due to the chitosan grafting, whereas the ferritin spherical structure were retained. Simulated digestion analysis showed that the FCMPs were more resistant to pepsin and trypsin digestion as compared with ferritin alone. Furthermore, FCMPs were employed as carrier to encapsulate epigallocatechin gallate (EGCG) molecules with an encapsulation ratio of 12.87% (w/w), and the resulting FCMPs-EGCG complexes showed a slow release of EGCG in simulated gastrointestinal tract. Interestingly, different types of food components displayed different effects in EGCG release behavior from the FCMPs, wherein proanthocyanidin, milk and soy protein inhibited the EGCG release. In addition, the absorption of EGCG encapsulated in FCMPs in Caco-2 monolayer model was significantly improved as compared with free EGCG. This work provides a novel nano-vehicle for fabricating core-shell systems in food and drug delivery domain. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced uptake and transport of (+)-catechin and (−)-epigallocatechin gallate in niosomal formulation by human intestinal Caco-2 cells

PubMed Central

Song, Qinxin; Li, Danhui; Zhou, Yongzhi; Yang, Jie; Yang, Wanqi; Zhou, Guohua; Wen, Jingyuan

2014-01-01

The aim of this study was to evaluate (+)-catechin and (−)-epigallocatechin gallate (EGCG) cellular uptake and transport across human intestinal Caco-2 cell monolayer in both the absence and presence of niosomal carrier in variable conditions. The effect of free drugs and drug-loaded niosomes on the growth of Caco-2 cells was studied. The effects of time, temperature, and concentration on drug cellular uptake in the absence or presence of its niosomal delivery systems were investigated. The intestinal epithelial membrane transport of the drug-loaded niosomes was examined using the monolayer of the human Caco-2 cells. The kinetics of transport, and the effect of temperature, adenosine triphosphate inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated protein 2 inhibitor, and the absorption enhancer on transport mechanism were investigated. It was found that the uptake of catechin, EGCG, and their niosomes by Caco-2 cells was 1.22±0.16, 0.90±0.14, 3.25±0.37, and 1.92±0.22 μg/mg protein, respectively (n=3). The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.68±0.16, 0.88±0.09, 2.39±0.31, and 1.42±0.24 cm/second (n=3) at 37°C, respectively. The transport was temperature- and energy-dependent. The inhibitors of permeability glycoprotein and multidrug resistance-associated protein 2 and the absorption enhancer significantly enhanced the uptake amount. Compared with the free drugs, niosomal formulation significantly enhanced drug absorption. Additionally, drug-loaded niosomes exhibited stronger stability and lower toxicity. These findings showed that the oral absorption of tea flavonoids could be improved by using the novel drug delivery systems. PMID:24855353

Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide

PubMed Central

Xu, Zhi-Xue; Zhang, Qiang; Ma, Gong-Li; Chen, Cong-Heng; He, Yan-Ming; Xu, Li-Hui; Zhang, Yuan; Zhou, Guang-Rong; Li, Zhen-Hua

2016-01-01

The abnormal fibrillation of human islet amyloid polypeptide (hIAPP) has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (−)-epigallocatechin gallate (EGCG) is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III)/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III) and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III) and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III) could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III)/EGCG complex in molar ratio of 1 : 1 as Al(EGCG)(H2O)2 could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes. PMID:28074190

The Bmi-1 helix-turn and ring finger domains are required for Bmi-1 antagonism of (-) epigallocatechin-3-gallate suppression of skin cancer cell survival.

PubMed

Balasubramanian, Sivaprakasam; Scharadin, Tiffany M; Han, Bingshe; Xu, Wen; Eckert, Richard L

2015-07-01

The Bmi-1 Polycomb group (PcG) protein is an important epigenetic regulator of chromatin status. Elevated Bmi-1 expression is observed in skin cancer and contributes to cancer cell survival. (-) Epigallocatechin-3-gallate (EGCG), an important green tea-derived cancer prevention agent, reduces Bmi-1 level resulting in reduced skin cancer cell survival. This is associated with increased p21(Cip1) and p27(Kip1) expression, reduced cyclin, and cyclin dependent kinase expression, and increased cleavage of apoptotic markers. These EGCG-dependent changes are attenuated by vector-mediated maintenance of Bmi-1 expression. In the present study, we identify Bmi-1 functional domains that are required for this response. Bmi-1 expression reverses the EGCG-dependent reduction in SCC-13 cell survival, but Bmi-1 mutants lacking the helix-turn-helix-turn-helix-turn (Bmi-1ΔHT) or ring finger (Bmi-1ΔRF) domains do not reverse the EGCG impact. The reduction in Ring1B ubiquitin ligase activity, observed in the presence of mutant Bmi-1, is associated with reduced ability of these mutants to interact with and activate Ring1B ubiquitin ligase, the major ligase responsible for the ubiquitination of histone H2A during chromatin condensation. This results in less chromatin condensation leading to increased tumor suppressor gene expression and reduced cell survival; thereby making the cells more susceptible to the anti-survival action of EGCG. We further show that these mutants act in a dominant-negative manner to inhibit the action of endogenous Bmi-1. Our results suggest that the HT and RF domains are required for Bmi-1 ability to maintain skin cancer cell survival in response to cancer preventive agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular identification for epigallocatechin-3-gallate-mediated antioxidant intervention on the H2O2-induced oxidative stress in H9c2 rat cardiomyoblasts.

PubMed

Chen, Wei-Cheng; Hsieh, Shih-Rong; Chiu, Chun-Hwei; Hsu, Ban-Dar; Liou, Ying-Ming

2014-06-09

Epigallocatechin-3-gallate (EGCG) has been documented for its beneficial effects protecting oxidative stress to cardiac cells. Previously, we have shown the EGCG-mediated cardiac protection by attenuating reactive oxygen species and cytosolic Ca2+ in cardiac cells during oxidative stress and myocardial ischemia. Here, we aimed to seek a deeper elucidation of the molecular anti-oxidative capabilities of EGCG in an H2O2-induced oxidative stress model of myocardial ischemia injury using H9c2 rat cardiomyoblasts. Proteomics analysis was used to determine the differential expression of proteins in H9c2 cells cultured in the conditions of control, 400 μM H2O2 exposure for 30 min with and/or without 10 to 20 μM EGCG pre-treatment. In this model, eight proteins associated with energy metabolism, mitochondrial electron transfer, redox regulation, signal transduction, and RNA binding were identified to take part in EGCG-ameliorating H2O2-induced injury in H9c2 cells. H2O2 exposure increased oxidative stress evidenced by increases in reactive oxygen species and cytosolic Ca2+ overload, increases in glycolytic protein, α-enolase, decreases in antioxidant protein, peroxiredoxin-4, as well as decreases in mitochondrial proteins, including aldehyde dehydrogenase-2, ornithine aminotransferase, and succinate dehydrogenase ubiquinone flavoprotein subunit. All of these effects were reversed by EGCG pre-treatment. In addition, EGCG attenuated the H2O2-induced increases of Type II inositol 3, 4-bisphosphate 4-phosphatase and relieved its subsequent inhibition of the downstream signalling for Akt and glycogen synthase kinase-3β (GSK-3β)/cyclin D1 in H9c2 cells. Pre-treatment with EGCG or GSK-3β inhibitor (SB 216763) significantly improved the H2O2-induced suppression on cell viability, phosphorylation of pAkt (S473) and pGSK-3β (S9), and level of cyclin D1 in cells. Collectively, these findings suggest that EGCG blunts the H2O2-induced oxidative effect on the Akt activity

Molecular identification for epigallocatechin-3-gallate-mediated antioxidant intervention on the H2O2-induced oxidative stress in H9c2 rat cardiomyoblasts

PubMed Central

2014-01-01

Background Epigallocatechin-3-gallate (EGCG) has been documented for its beneficial effects protecting oxidative stress to cardiac cells. Previously, we have shown the EGCG-mediated cardiac protection by attenuating reactive oxygen species and cytosolic Ca2+ in cardiac cells during oxidative stress and myocardial ischemia. Here, we aimed to seek a deeper elucidation of the molecular anti-oxidative capabilities of EGCG in an H2O2-induced oxidative stress model of myocardial ischemia injury using H9c2 rat cardiomyoblasts. Results Proteomics analysis was used to determine the differential expression of proteins in H9c2 cells cultured in the conditions of control, 400 μM H2O2 exposure for 30 min with and/or without 10 to 20 μM EGCG pre-treatment. In this model, eight proteins associated with energy metabolism, mitochondrial electron transfer, redox regulation, signal transduction, and RNA binding were identified to take part in EGCG-ameliorating H2O2-induced injury in H9c2 cells. H2O2 exposure increased oxidative stress evidenced by increases in reactive oxygen species and cytosolic Ca2+ overload, increases in glycolytic protein, α-enolase, decreases in antioxidant protein, peroxiredoxin-4, as well as decreases in mitochondrial proteins, including aldehyde dehydrogenase-2, ornithine aminotransferase, and succinate dehydrogenase ubiquinone flavoprotein subunit. All of these effects were reversed by EGCG pre-treatment. In addition, EGCG attenuated the H2O2-induced increases of Type II inositol 3, 4-bisphosphate 4-phosphatase and relieved its subsequent inhibition of the downstream signalling for Akt and glycogen synthase kinase-3β (GSK-3β)/cyclin D1 in H9c2 cells. Pre-treatment with EGCG or GSK-3β inhibitor (SB 216763) significantly improved the H2O2-induced suppression on cell viability, phosphorylation of pAkt (S473) and pGSK-3β (S9), and level of cyclin D1 in cells. Conclusions Collectively, these findings suggest that EGCG blunts the H2O2-induced oxidative

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR

PubMed Central

Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

2016-01-01

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts ‘on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment. PMID:27035618

Comparison of α-glucosyl hesperidin of citrus fruits and epigallocatechin gallate of green tea on the Loss of Rotavirus Infectivity in Cell Culture.

PubMed

Lipson, Steven M; Ozen, Fatma S; Louis, Samantha; Karthikeyan, Laina

2015-01-01

A number of secondary plant metabolites (e.g., flavonoids) possess antiviral/antimicrobial activity. Most flavonoids, however, are difficult to study, as they are immiscible in water-based systems. The relatively new semisynthetic α-glucosyl hesperitin (GH), and the natural plant product epigallocatechin gallate (EGCG) are unique among most flavonoids, as these flavonoids are highly soluble. The antiviral activity of these plant metabolites were investigated using the rotavirus as a model enteric virus system. Direct loss of virus structural integrity in cell-free suspension and titration of amplified RTV in host cell cultures was measured by a quantitative enzyme-linked immunosorbent assay (qEIA). After 30 min. 100 × 10(3) μg/ml GH reduced RTV antigen levels by ca. 90%. The same compound reduced infectivity (replication in cell culture) by a similar order of magnitude 3 to 4 days post inoculation. After 3 days in culture, EGCG concentrations of 80, 160, and 320 μg/ml reduced RTV infectivity titer levels to ca. 50, 20, and 15% of the control, respectively. Loss of RTV infectivity titers occurred following viral treatment by parallel testing of both GH and EGCG, with the latter, markedly more effective. Cytotoxicity testing showed no adverse effects by the phenolic concentrations used in this study. The unique chemical structure of each flavonoid rather than each phenolic's inherent solubility may be ascribed to those marked differences between each molecule's antiviral (anti-RTV) effects. The solubility of EGCG and GH obviated our need to use potentially confounding or obfuscating carrier molecules (e.g., methanol, ethanol, DMSO) denoting our use of a pure system environ. Our work further denotes the need to address the unique chemical nature of secondary plant metabolites before any broad generalizations in flavonoid (antiviral) activity may be proposed.

Difference of EGCg adhesion on cell surface between Staphylococcus aureus and Escherichia coli visualized by electron microscopy after novel indirect staining with cerium chloride.

PubMed

Nakayama, Motokazu; Shigemune, Naofumi; Tsugukuni, Takashi; Tokuda, Hajime; Miyamoto, Takahisa

2011-07-01

We developed a novel method using indirect staining with cerium chloride for visualization of the catechin derivative epigallocatechin gallate (EGCg) on the surface of particles, i.e., polystyrene beads and bacterial cells, by electron microscopy. The staining method is based on the fact that in an alkaline environment, EGCg produces hydrogen peroxide, and then hydrogen peroxide reacts with cerium, resulting in a cerium hydroperoxide precipitate. This precipitate subsequently reacts with EGCg to produce larger deposits. The amount of precipitate is proportional to the amount of EGCg. Highly EGCg-sensitive Staphylococcus aureus and EGCg-resistant Escherichia coli were treated with EGCg under various pH conditions. Transmission electron microscopy observation showed that the amount of deposits on S. aureus increased with an increase in EGCg concentration. After treating bacterial cells with 0.5mg/mL EGCg (pH 6.0), attachment of EGCg was significantly lower to E. coli than to S. aureus. This is the first report that shows differences in affinity of EGCg to the cell surfaces of Gram-positive and -negative bacteria by electron microscopy. Copyright © 2011 Elsevier B.V. All rights reserved.

The Bmi-1 helix–turn and ring finger domains are required for Bmi-1 antagonism of (–) epigallocatechin-3-gallate suppression of skin cancer cell survival

PubMed Central

Balasubramanian, Sivaprakasam; Scharadin, Tiffany M.; Han, Bingshe; Xu, Wen; Eckert, Richard L.

2016-01-01

The Bmi-1 Polycomb group (PcG) protein is an important epigenetic regulator of chromatin status. Elevated Bmi-1 expression is observed in skin cancer and contributes to cancer cell survival. (–) Epigallocatechin-3-gallate (EGCG), an important green tea-derived cancer prevention agent, reduces Bmi-1 level resulting in reduced skin cancer cell survival. This is associated with increased p21Cip1 and p27Kip1 expression, reduced cyclin, and cyclin dependent kinase expression, and increased cleavage of apoptotic markers. These EGCG-dependent changes are attenuated by vector-mediated maintenance of Bmi-1 expression. In the present study, we identify Bmi-1 functional domains that are required for this response. Bmi-1 expression reverses the EGCG-dependent reduction in SCC-13 cell survival, but Bmi-1 mutants lacking the helix–turn–helix–turn–helix–turn (Bmi-1ΔHT) or ring finger (Bmi-1ΔRF) domains do not reverse the EGCG impact. The reduction in Ring1B ubiquitin ligase activity, observed in the presence of mutant Bmi-1, is associated with reduced ability of these mutants to interact with and activate Ring1B ubiquitin ligase, the major ligase responsible for the ubiquitination of histone H2A during chromatin condensation. This results in less chromatin condensation leading to increased tumor suppressor gene expression and reduced cell survival; thereby making the cells more susceptible to the anti-survival action of EGCG. We further show that these mutants act in a dominant-negative manner to inhibit the action of endogenous Bmi-1. Our results suggest that the HT and RF domains are required for Bmi-1 ability to maintain skin cancer cell survival in response to cancer preventive agents. PMID:25843776

Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate.

PubMed

Saldanha, Sabita N; Kala, Rishabh; Tollefsbol, Trygve O

2014-05-15

Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with the combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Possible role of antioxidative capacity of (-)-epigallocatechin-3-gallate treatment in morphological and neurobehavioral recovery after sciatic nerve crush injury.

PubMed

Renno, Waleed M; Benov, Ludmil; Khan, Khalid M

2017-11-01

OBJECTIVE This study examined the capacity of the major polyphenolic green tea extract (-)-epigallocatechin-3-gallate (EGCG) to suppress oxidative stress and stimulate the recovery and prompt the regeneration of sciatic nerve after crush injury. METHODS Adult male Wistar rats were randomly assigned to one of 4 groups: 1) Naïve, 2) Sham (sham injury, surgical control group), 3) Crush (sciatic nerve crush injury treated with saline), and 4) Crush+EGCG (sciatic nerve crush injury treated with intraperitoneally administered EGCG, 50 mg/kg). All animals were tested for motor and sensory neurobehavioral parameters throughout the study. Sciatic nerve and spinal cord tissues were harvested and processed for morphometric and stereological analysis. For the biochemical assays, the time points were Day 1, Day 7, Day 14, and Day 28 after nerve injury. RESULTS After sciatic nerve crush injury, the EGCG-treated animals (Crush+EGCG group) showed significantly better recovery of foot position and toe spread and 50% greater improvement in motor recovery than the saline-treated animals (Crush group). The Crush+EGCG group displayed an early hopping response at the beginning of the 3rd week postinjury. Animals in the Crush+EGCG group also showed a significant reduction in mechanical allodynia and hyperalgesia latencies and significant improvement in recovery from nociception deficits in both heat withdrawal and tail flick withdrawal latencies compared with the Crush group. In both the Crush+EGCG and Crush groups, quantitative evaluation revealed significant morphological evidence of neuroregeneration according to the following parameters: mean cross-sectional area of axons, myelin thickness in the sciatic nerve (from Week 4 to Week 8), increase of myelin basic protein concentration and gene expression in both the injured sciatic nerve and spinal cord, and fiber diameter to axon diameter ratio and myelin thickness to axon diameter ratio at Week 2 after sciatic nerve injury. However

EGCG in Green Tea Induces Aggregation of HMGB1 Protein through Large Conformational Changes with Polarized Charge Redistribution

NASA Astrophysics Data System (ADS)

Meng, Xuan-Yu; Li, Baoyu; Liu, Shengtang; Kang, Hongsuk; Zhao, Lin; Zhou, Ruhong

2016-02-01

As a major effective component in green tea, (-)-epigallocatechin-3-gallate (EGCG)’s potential benefits to human health have been widely investigated. Recent experimental evidences indicate that EGCG can induce the aggregation of HMGB1 protein, a late mediator of inflammation, which subsequently stimulates the autophagic degradation and thus provides protection from lethal endotoxemia and sepsis. In this study, we use molecular dynamics (MD) simulations to explore the underlying molecular mechanism of this aggregation of HMGB1 facilitated by EGCG. Our simulation results reveal that EGCG firmly binds to HMGB1 near Cys106, which supports previous preliminary experimental evidence. A large HMGB1 conformational change is observed, where Box A and Box B, two homogenous domains of HMGB1, are repositioned and packed together by EGCG. This new HMGB1 conformation has large molecular polarity and distinctive electrostatic potential surface. We suggest that the highly polarized charge distribution leads to the aggregation of HMGB1, which differs from the previous hypothesis that two HMGB1 monomers are linked by the dimer of EGCG. Possible aggregating modes have also been investigated with potential of mean force (PMF) calculations. Finally, we conclude that the conformation induced by EGCG is more aggregation-prone with higher binding free energies as compared to those without EGCG.

Separation of catechin constituents from five tea cultivars using high-speed counter-current chromatography.

PubMed

Kumar, N Savitri; Rajapaksha, Maheshinie

2005-08-12

Catechins were extracted from five different tea (Camellia sinensis L.) cultivars. High-speed counter-current chromatography was found to be an efficient method for the separation of seven catechins from the catechin extracts. High-performance liquid chromatography was used to assess the purity of the catechins isolated. Epigallocatechin gallate (EGCG), epicatechin gallate (ECG) and epigallocatechin (EGC) of high purity (91-99%) were isolated in high yield after a single high-speed counter-current chromatography run. The two-phase solvent mixtures used for the separation of the catechin extracts were hexane:ethyl acetate:methanol:water (1:6:1:6 for TRI 2023); (1:7:1:7 for TRI 2025 and TRI 2043); (1:5:1:5 for TRI 3079) and (1:6.5:1:6.5 for TRI 4006). Fresh tea shoots from the tea cultivar TRI 2023 (150 g) gave 440 mg of 96% pure EGCG while TRI 2025 (235 g) gave 347 mg of 99% pure EGCG and 40 mg of 97% ECG, and TRI 3079 (225 g) gave 432 mg of 97% pure EGCG and 32 mg of 96% pure ECG. Tea cultivar TRI 4006 (160 g) gave EGCG (272 mg, 96% pure) and EGC (104 mg, 90% pure). 1H and 13C NMR chemical shifts for catechin gallate (CG), EGC, ECG, EGCG and epigallocatechin 3,5-di-O-gallate (EGCDG) in CD3OD were also recorded.

Radiation- and Depleted Uranium-Induced Carcinogenesis Studies: Characterization of the Carcinogenic Process and Development of Medical Countermeasures

DTIC Science & Technology

2005-01-01

drug development. 3.2 Candidate Agents: Phenylacetate and Epigallocatechin Gallate Phenylacetate (PA) is an attractive candidate for our studies...The polyphenol, epigallocathechin-3 gallate ( EGCG ), a major constituent of green tea, is also an attractive candidate for low-dose radiation...preventive agents. Part 1: chemopreventive potential of Epigallocatechin gallate , cimigenol, cimigenol-3,15-dione, and related compounds, Bioorganic Medical

Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer

PubMed Central

Siddiqui, Imtiaz A.; Asim, Mohammad; Hafeez, Bilal B.; Adhami, Vaqar M.; Tarapore, Rohinton S.; Mukhtar, Hasan

2011-01-01

Androgen deprivation therapy is the major treatment for advanced prostate cancer (PCa). However, it is a temporary remission, and the patients almost inevitably develop hormone refractory prostate cancer (HRPC). HRPC is almost incurable, although most HRPC cells still express androgen receptor (AR) and depend on the AR for growth, making AR a prime drug target. Here, we provide evidence that epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, is a direct antagonist of androgen action. In silico modeling and FRET-based competition assay showed that EGCG physically interacts with the ligand-binding domain of AR by replacing a high-affinity labeled ligand (IC50 0.4 μM). The functional consequence of this interaction was a decrease in AR-mediated transcriptional activation, which was due to EGCG mediated inhibition of interdomain N-C termini interaction of AR. Treatment with EGCG also repressed the transcriptional activation by a hotspot mutant AR (T877A) expressed ectopically as well as the endogenous AR mutant. As the physiological consequence of AR antagonism, EGCG repressed R1881-induced PCa cell growth. In a xenograft model, EGCG was found to inhibit AR nuclear translocation and protein expression. We also observed a significant down-regulation of androgen-regulated miRNA-21 and up-regulation of a tumor suppressor, miRNA-330, in tumors of mice treated with EGCG. Taken together, we provide evidence that EGCG functionally antagonizes androgen action at multiple levels, resulting in inhibition of PCa growth.—Siddiqui, I. A., Asim, M., Hafeez, B. B., Adhami, V. M., Tarapore, R. S., Mukhtar, H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. PMID:21177307

Functional Characterization of Epitheaflagallin 3-O-Gallate Generated in Laccase-Treated Green Tea Extracts in the Presence of Gallic Acid.

PubMed

Itoh, Nobuya; Kurokawa, Junji; Isogai, Yasuhiro; Ogasawara, Masaru; Matsunaga, Takayuki; Okubo, Tsutomu; Katsube, Yuji

2017-12-06

Epitheaflagallin (ETFG) and epitheaflagallin 3-O-gallate (ETFGg) are minor polyphenols in black tea extract that are enzymatically synthesized from epigallocatechin (EGC) and epigallocatechin gallate (EGCg), respectively, in green tea extract via laccase oxidation in the presence of gallic acid. The constituents of laccase-treated green tea extract in the presence of gallic acid are thus quite different from those of nonlaccase-treated green tea extract: EGC and EGCg are present in lower concentrations, and ETFG and ETFGg are present in higher concentrations. Additionally, laccase-treated green tea extract contains further polymerized catechin derivatives, comparable with naturally fermented teas such as oolong tea and black tea. We found that ETFGg and laccase-treated green tea extracts exhibit versatile physiological functions in vivo and in vitro, including antioxidative activity, pancreatic lipase inhibition, Streptococcus sorbinus glycosyltransferase inhibition, and an inhibiting effect on the activity of matrix metalloprotease-1 and -3 and their synthesis by human gingival fibroblasts. We confirmed that these inhibitory effects of ETFGg in vitro match well with the results obtained by docking simulations of the compounds with their target enzymes or noncatalytic protein. Thus, ETFGg and laccase-treated green tea extracts containing ETFGg are promising functional food materials with potential antiobesity and antiperiodontal disease activities.

Evaluation of plasma antioxidant activity in rats given excess EGCg with reference to endogenous antioxidants concentrations and assay methods.

PubMed

Yokotani, Kaori; Umegaki, Keizo

2017-02-01

The contribution of (-)-epigallocatechin gallate (EGCg) intake to in vivo antioxidant activity is unclear, even with respect to plasma. In this study, we examined how administration of EGCg contributes to plasma antioxidant activity, relative to its concentration, endogenous antioxidants, and assay methods, namely oxygen radical absorbance capacity (ORAC) and ferric reducing/antioxidant power (FRAP). Administration of EGCg (500 mg/kg) to rats increased plasma EGCg (4μmol/L as free form) and ascorbic acid (1.7-fold), as well as ORAC (1.2-fold) and FRAP (3-fold) values. The increase in plasma ascorbic acid following EGCg administration was accompanied by its relocation from the adrenal glands and lymphocytes into plasma, and was related to the increase in FRAP. Plasma deproteinization and assays in plasma model solutions revealed that protein levels significantly contributed to ORAC values, where <3 μmol/L EGCg in the presence of protein exhibited minimal antioxidant activity, as measured by both FRAP and ORAC. As the concentration of plasma ascorbic acid was not influenced by deproteinization, differences in FRAP values with and without deproteinization were estimated to determine the contribution of enhanced ascorbic acid attributable to EGCg administration. These results will help to understand the points that should be considered when evaluating EGCg antioxidant activity in plasma.

Reduction in promotor methylation utilizing EGCG (epigallocatechin-3-gallate) restores RXRα expression in human colon cancer cells.

PubMed

Morris, Jay; Moseley, Vondina R; Cabang, April B; Coleman, Katie; Wei, Wei; Garrett-Mayer, Elizabeth; Wargovich, Michael J

2016-06-07

Silencing of regulatory genes through hypermethylation of CpG islands is an important mechanism in tumorigenesis. In colon cancer, RXRα, an important dimerization partner with other nuclear transcription factors, is silenced through this mechanism. We previously found that colon tumors in ApcMin/+ mice had diminished levels of RXRα protein and expression levels of this gene were restored by treatment with a green tea intervention, due to reduced promoter methylation of RXRα. We hypothesized that CIMP+ cell lines, which epigenetically silence key regulatory genes would also evidence silencing of RXRα and EGCG treatment would restore its expression. We indeed found EGCG to restore RXRα activity levels in the human cell lines, in a dose dependent manner and reduced RXRα promoter methylation. EGCG induced methylation changes in several other colon cancer related genes but did not cause a decrease in global methylation. Numerous epidemiological reports have shown the benefits of green tea consumption in reducing colon cancer risk but to date no studies have shown that the risk reduction may be related to the epigenetic restoration by tea polyphenols. Our results show that EGCG modulates the reversal of gene silencing involved in colon carcinogenesis providing a possible avenue for colon cancer prevention and treatment.

Cellular Targets of Dietary Polyphenol Resveratrol

DTIC Science & Technology

2005-03-01

attempts to generate affinity columns tagged with other polyphenols, e.g., epigallocatechin gallate ( EGCG ). Conceivably such columns, if generated, would...Similar affinity chromatography with the related polyphenol Epigallocatechin gallate does not produce similar results.” Answer: We did not make...addition, the PI does not provid expression. If there is “increased ex many bind the resveratrol affinity co related polyphenol Epigallocatechin Response

A 3-day EGCG-supplementation reduces interstitial lactate concentration in skeletal muscle of overweight subjects

PubMed Central

Most, Jasper; van Can, Judith G P; van Dijk, Jan-Willem; Goossens, Gijs H.; Jocken, Johan; Hospers, Jeannette J.; Bendik, Igor; Blaak, Ellen E.

2015-01-01

Green tea, particularly epigallocatechin-3-gallate (EGCG), may affect body weight and composition, possibly by enhancing fat oxidation. The aim of this double-blind, randomized placebo-controlled cross-over study was to investigate whether 3-day supplementation with EGCG (282mg/day) stimulates fat oxidation and lipolysis in 24 overweight subjects (age = 30 ± 2yrs, BMI = 27.7 ± 0.3 kg/m2). Energy expenditure, substrate metabolism and circulating metabolites were determined during fasting and postprandial conditions. After 6 h, a fat biopsy was collected to examine gene expression. In 12 subjects, skeletal muscle glycerol, glucose and lactate concentrations were determined using microdialysis. EGCG-supplementation did not alter energy expenditure and substrate oxidation compared to placebo. Although EGCG reduced postprandial circulating glycerol concentrations (P = 0.015), no difference in skeletal muscle lipolysis was observed. Fasting (P = 0.001) and postprandial (P = 0.003) skeletal muscle lactate concentrations were reduced after EGCG-supplementation compared to placebo, despite similar tissue blood flow. Adipose tissue leptin (P = 0.05) and FAT/CD36 expression (P = 0.08) were increased after EGCG compared to placebo. In conclusion, 3-day EGCG-supplementation decreased postprandial plasma glycerol concentrations, but had no significant effects on skeletal muscle lipolysis and whole-body fat oxidation in overweight individuals. Furthermore, EGCG decreased skeletal muscle lactate concentrations, which suggest a shift towards a more oxidative muscle phenotype. PMID:26647963

Project INSPIRE-HBCU Undergraduate Collaborative Summer Training Program to Inspire Students in Prostate Cancer Research

DTIC Science & Technology

2008-02-01

gallate ( EGCG ). It has been shown that tea polyphenols such as EGCG potently and specifically inhibit chymotrypsin-like activity of the proteasome...autochthonous mouse model of prostate cancer; 2004 2. Ahmad, Nihal; Green Tea Constituent Epigallocatechin -3- Gallate and Induction of apoptosis and cell...such as multiple myeloma. - It has been shown that tea polyphenols, such as (-)- EGCG , potently and specifically inhibit chymotrypsin-like activity of

Acute EGCG Supplementation Reverses Endothelial Dysfunction in Patients with Coronary Artery Disease

PubMed Central

Widlansky, Michael E.; Hamburg, Naomi M.; Anter, Elad; Holbrook, Monika; Kahn, David F.; Elliott, James G.; Keaney, John F.; Vita, Joseph A.

2013-01-01

Background Epidemiological studies demonstrate an inverse relation between dietary flavonoid intake and cardiovascular risk. Recent studies with flavonoid-containing beverages suggest that the benefits of these nutrients may relate, in part, to improved endothelial function. Objective We hypothesized that dietary supplementation with epigallocatechin gallate (EGCG), a major catechin in tea, would improve endothelial function in humans. Design We examined the effects of EGCG on endothelial function in a double blind, placebo-controlled, crossover design study. We measured brachial artery flow-mediated dilation by vascular ultrasound at six time points: prior to treatment with EGCG or placebo, two hours after an initial dose of EGCG (300 mg) or placebo, and after two weeks of treatment with EGCG (150 mg twice daily) or placebo. The order of treatments (EGCG or placebo) was randomized and there was a one-week washout period between treatments. Results A total of 42 subjects were enrolled, and brachial artery flow-mediated dilation improved from 7.1±4.1 to 8.6±4.7% two hours after the first dose of 300mg of EGCG (P=0.01), but was similar to baseline (7.8±4.2%, P=0.12) after two weeks of treatment with the final measurements made approximately 14 hours after the last dose. Placebo treatment had no significant effect, and there were no changes in reactive hyperemia or the response to sublingual nitroglycerin. The changes in vascular function paralleled plasma EGCG concentrations, which increased from 2.6±10.9 to 92.8±78.7 ng/ml after acute EGCG (P<0.001), but were unchanged from baseline after two weeks of treatment (3.4±13.1 ng/ml). Conclusion EGCG acutely improves endothelial function in humans with coronary artery disease, and may account for a portion of the beneficial effects of flavonoid-rich food on endothelial function. PMID:17536120

Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease.

PubMed

Widlansky, Michael E; Hamburg, Naomi M; Anter, Elad; Holbrook, Monika; Kahn, David F; Elliott, James G; Keaney, John F; Vita, Joseph A

2007-04-01

Epidemiological studies demonstrate an inverse relation between dietary flavonoid intake and cardiovascular risk. Recent studies with flavonoid-containing beverages suggest that the benefits of these nutrients may relate, in part, to improved endothelial function. We hypothesized that dietary supplementation with epigallocatechin gallate (EGCG), a major catechin in tea, would improve endothelial function in humans. We examined the effects of EGCG on endothelial function in a double blind, placebo-controlled, crossover design study. We measured brachial artery flow-mediated dilation by vascular ultrasound at six time points: prior to treatment with EGCG or placebo, two hours after an initial dose of EGCG (300 mg) or placebo, and after two weeks of treatment with EGCG (150 mg twice daily) or placebo. The order of treatments (EGCG or placebo) was randomized and there was a one-week washout period between treatments. A total of 42 subjects completed the study, and brachial artery flow-mediated dilation improved from 7.1 +/- 4.1 to 8.6 +/- 4.7% two hours after the first dose of 300 mg of EGCG (P = 0.01), but was similar to baseline (7.8 +/- 4.2%, P = 0.12) after two weeks of treatment with the final measurements made approximately 14 hours after the last dose. Placebo treatment had no significant effect, and there were no changes in reactive hyperemia or the response to sublingual nitroglycerin. The changes in vascular function paralleled plasma EGCG concentrations, which increased from 2.6 +/- 10.9 to 92.8 +/- 78.7 ng/ml after acute EGCG (P < 0.001), but were unchanged from baseline after two weeks of treatment (3.4 +/- 13.1 ng/ml). EGCG acutely improves endothelial function in humans with coronary artery disease, and may account for a portion of the beneficial effects of flavonoid-rich food on endothelial function.

Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (-)-epigallocatechin gallate-treated cells.

PubMed

Watanabe, Tatsuro; Kuramochi, Hiromi; Takahashi, Atsushi; Imai, Kazue; Katsuta, Naoko; Nakayama, Tomonobu; Fujiki, Hirota; Suganuma, Masami

2012-05-01

To understand how nanomechanical stiffness affects metastatic potential, we studied the relationship between cell migration, a characteristic of metastasis, and cell stiffness using atomic force microscopy (AFM), which can measure stiffness (elasticity) of individual living cells. Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (-)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young's modulus were 350.8 ± 4.8 Pa for B16-F10 cells, 661.9 ± 16.5 Pa for B16-BL6 cells, and 727.2 ± 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis.

Effects of the vegetable polyphenols epigallocatechin-3-gallate, luteolin, apigenin, myricetin, quercetin, and cyanidin in primary cultures of human retinal pigment epithelial cells

PubMed Central

Chen, Rui; Grosche, Antje; Reichenbach, Andreas; Wiedemann, Peter; Bringmann, Andreas; Kohen, Leon

2014-01-01

Purpose Vegetable polyphenols (bioflavonoids) have been suggested to represent promising drugs for treating cancer and retinal diseases. We compared the effects of various bioflavonoids (epigallocatechin-3-gallate [EGCG], luteolin, apigenin, myricetin, quercetin, and cyanidin) on the physiological properties and viability of cultured human retinal pigment epithelial (RPE) cells. Methods Human RPE cells were obtained from several donors within 48 h of death. Secretion of vascular endothelial growth factor (VEGF) was determined with enzyme-linked immunosorbent assay. Messenger ribonucleic acid levels were determined with real-time reverse transcription polymerase chain reaction. Cellular proliferation was investigated with a bromodeoxyuridine immunoassay, and chemotaxis was examined with a Boyden chamber assay. The number of viable cells was determined by Trypan Blue exclusion. Apoptosis and necrosis rates were determined with a DNA fragmentation enzyme-linked immunosorbent assay. The phosphorylation level of signaling proteins was revealed by western blotting. Results With the exception of EGCG, all flavonoids tested decreased dose-dependently the RPE cell proliferation, migration, and secretion of VEGF. EGCG inhibited the secretion of VEGF evoked by CoCl2-induced hypoxia. The gene expression of VEGF was reduced by myricetin at low concentrations and elevated at higher concentrations. Luteolin, apigenin, myricetin, and quercetin induced significant decreases in the cell viability at higher concentration, by triggering cellular necrosis. Cyanidin reduced the rate of RPE cell necrosis. Myricetin caused caspase-3 independent RPE cell necrosis mediated by free radical generation and activation of calpain and phospholipase A2. The myricetin- and quercetin-induced RPE cell necrosis was partially inhibited by necrostatin-1, a blocker of programmed necrosis. Most flavonoids tested diminished the phosphorylation levels of extracellular signal-regulated kinases 1/2 and Akt

Radical-scavenging abilities and antioxidant properties of theaflavins and their gallate esters in H2O2-mediated oxidative damage system in the HPF-1 cells.

PubMed

Yang, Ziyin; Jie, Guoliang; Dong, Fang; Xu, Yi; Watanabe, Naoharu; Tu, Youying

2008-08-01

The antioxidant properties of theaflavins and their gallate esters, namely theaflavin (TF1), theaflavin-3(3')-gallate (TF2) and theaflavin-3,3'-digallate (TF3) were investigated by comparing with epigallocatechin gallate (EGCG). The order of hydroxyl radicals-scavenging ability was TF3>TF2>TF1>EGCG. The order of 2,2-diphenyl-1-picrylhydrazyl scavenging ability was TF3>TF2>EGCG>TF1. TF1, TF2, and TF3 showed more effective effects than EGCG in protection against H2O2-mediated damage in HPF-1 cells. TF2 was the most potent accelerant of HPF-1 cell proliferation. TF1, TF2 and TF3 suppressed the accumulation of intracellular reactive species in H2O2-mediated damage HPF-1 cells. Pre-treated for 2h and eliminated from the cells, TF1 and TF3 still showed protective effects against H2O2-mediated damage in HPF-1 cells. This suggests that the protective effects of TF1 and TF3 on oxidative damage HPF-1 cells may be responsible for other mechanisms, rather than only scavenging the already formed reactive species. It remains to be determined whether TF1 and TF3 improved the normal HPF-1 cell resistive abilities toward radical-damage in pre-treatment. Further studies of the effects of theaflavins on some enzymes or signal transduction in the normal HPF-1 cells are underway.

Epigallocatechin-3-gallate prevents lipid peroxidation and enhances antioxidant defense system via modulating hepatic nuclear transcription factors in heat-stressed quails.

PubMed

Sahin, K; Orhan, C; Tuzcu, M; Ali, S; Sahin, N; Hayirli, A

2010-10-01

Epigallocatechin-3-gallate (EGCG), a polyphenol derived from green tea, exerts antioxidant effects. Oxidative stress is one of the consequences of heat stress (HS), which also depresses performance in poultry. This experiment was conducted to elucidate the action mode of EGCG in alleviation of oxidative stress in heat-stressed quail (Coturnix coturnix japonica). A total of 180 five-week-old female Japanese quails were reared either at 22°C for 24 h/d (thermoneutral, TN) or 34°C for 8 h/d (HS) for 12 wk. Birds in both environments were randomly fed 1 of 3 diets: basal diet and basal diet added with 200 or 400 mg of EGCG/kg of diet. Each of the 2×3 factorially arranged groups was replicated in 10 cages, each containing 3 quails. Performance variables [feed intake (FI) and egg production (EP)], oxidative stress biomarkers [malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)] and hepatic transcription factors [nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)] were analyzed using 2-way ANOVA. Exposure to HS caused reductions in FI by 9.7% and EP by 14.4%, increased hepatic MDA level by 84.8%, and decreased hepatic SOD, CAT, and GSH-Px activities by 25.8, 52.3, and 45.5%, respectively (P<0.0001 for all). The hepatic NF-κB expression was greater (156 vs. 82%) and Nrf2 expression was lower (84 vs. 118%) for quails reared under the HS environment than for those reared under the TN environment (P<0.0001 for both). In response to increasing supplemental EGCG level, there were linear increases in FI from 29.6 to 30.9 g/d and EP from 84.3 to 90.1%/d, linear decreases in hepatic MDA level from 2.82 to 1.72 nmol/g and Nrf2 expression from 77.5 to 123.3%, and linear increases in hepatic SOD (146.4 to 182.2), CAT (36.2 to 47.1), and GSH-Px (13.5 to 18.5) activities (U/mg of protein) and NF-κB expression (149.7 to 87.3%) (P<0.0001 for all). Two

Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells.

PubMed

Hossain, Md Motarab; Banik, Naren L; Ray, Swapan K

2012-08-01

Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (-)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-κB), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro

Skin Delivery of EGCG and Silibinin: Potential of Peptide Dendrimers for Enhanced Skin Permeation and Deposition.

PubMed

Shetty, Pallavi Krishna; Manikkath, Jyothsna; Tupally, Karnaker; Kokil, Ganesh; Hegde, Aswathi R; Raut, Sushil Y; Parekh, Harendra S; Mutalik, Srinivas

2017-08-01

The aim of the present study was to evaluate the ability of the peptide dendrimers to facilitate transdermal delivery of antioxidants, silibinin, and epigallocatechin-3-gallate (EGCG). Drug-peptide dendrimer complexes were prepared and evaluated for their ability to permeate across the skin. The data revealed the ready formation of complexes between drug and peptide dendrimer in a molar ratio of 1:1. In vitro permeation studies using excised rat skin and drug-peptide dendrimer complexes showed highest values for cumulative drug permeation at the end of 12 h (Q 12 ), with corresponding permeability coefficient (Kp) and enhancement ratio values also determined at this time point. With silibinin, 3.96-, 1.81-, and 1.06-fold increase in skin permeation was observed from silibinin-peptide dendrimer complex, simultaneous application of silibinin + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. With EGCG, 9.82-, 2.04-, and 1.72-fold increase in skin permeation was observed from EGCG-peptide dendrimer complex, simultaneous application of EGCG + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. The present study demonstrates the application of peptide dendrimers in effectively delivering antioxidants such as EGCG and silibinin into the skin, thus offering the potential to provide antioxidant effects when delivered via appropriately formulated topical preparations.

Effect of catechin and its derivatives on inhibition of polyphenoloxidase and melanosis of Pacific white shrimp.

PubMed

Sae-Leaw, Thanasak; Benjakul, Soottawat; Simpson, Benjamin K

2017-04-01

This study aimed to investigate the effect of tea catechin (C) and 4 of its derivatives on the Pacific white shrimp PPO inhibition and melanosis during refrigerated storage. Epigallocatechin gallate (EGCG) exhibited the highest inhibition towards PPO, followed by C. Inhibitory activity of all compounds tested was in a dose dependent manner (0.1-2.0 mM). Based on activity staining, EGCG most effectively inhibited PPO. For inhibition kinetic studies, C and epicatechin (EC) showed uncompetitive type, whereas epicatechin gallate (ECG), epigallocatechin (EGC) and EGCG exhibited mixed type inhibition. When whole shrimps were treated with EGCG solution at various concentrations (0.25-0.75%), those treated with 0.5 or 0.75% EGCG had lower melanosis scores throughout storage for 10 days at 4 °C, compared with the control and the 1.25% sodium metabisulfite treated samples ( P  < 0.05). Therefore, EGCG could be used as a potential inhibitor for melanosis in raw Pacific white shrimp during refrigerated storage.

Determination of catechins and catechin gallates in tissues by liquid chromatography with coulometric array detection and selective solid phase extraction.

PubMed

Chu, Kai On; Wang, Chi Chiu; Chu, Ching Yan; Rogers, Michael Scott; Choy, Kwong Wai; Pang, Chi Pui

2004-10-25

Catechins levels in organ tissues, particularly liver, determined by published methods are unexpectedly low, probably due to the release of oxidative enzymes, metal ions and reactive metabolites from tissue cells during homogenization and to the pro-oxidant effects of ascorbic acid during sample processing in the presence of metal ions. We describe a new method for simultaneous analysis of eight catechins in tissue: (+)-catechin (C), (-)-epicatechin (EC), (-)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-catechin gallate (CG), (-)-epicatechin gallate (ECG), (-)-gallocatechin gallate (GCG) and (-)-epigallocatechin gallate (EGCG) (Fig. 1). The new extraction procedure utilized a methanol/ethylacetate/dithionite (2:1:3) mixture during homogenization for simultaneous enzyme precipitation and antioxidant protection. Selective solid phase extraction was used to remove most interfering bio-matrices. Reversed phase HPLC with CoulArray detection was used to determine the eight catechins simultaneously within 25 min. Good linearity (>0.9922) was obtained in the range 20-4000 ng/g. The coefficients of variance (CV) were less than 5%. Absolute recovery ranged from 62 to 96%, accuracy 92.5 +/- 4.5 to 104.9 +/- 6%. The detection limit was 5 ng/g. This method is capable for determining catechins in rat tissues of liver, brain, spleen, and kidney. The method is robust, reproducible, with high recovery, and has been validated for both in vitro and in vivo sample analysis.

EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways.

PubMed

Liu, Shumin; Sun, Zhengwu; Chu, Peng; Li, Hailong; Ahsan, Anil; Zhou, Ziru; Zhang, Zonghui; Sun, Bin; Wu, Jingjun; Xi, Yalin; Han, Guozhu; Lin, Yuan; Peng, Jinyong; Tang, Zeyao

2017-05-01

Homocysteine (Hcy) induced vascular endothelial injury leads to the progression of endothelial dysfunction in atherosclerosis. Epigallocatechin gallate (EGCG), a natural dietary antioxidant, has been applied to protect against atherosclerosis. However, the underlying protective mechanism of EGCG has not been clarified. The present study investigated the mechanism of EGCG protected against Hcy-induced human umbilical vein endothelial cells (HUVECs) apoptosis. Methyl thiazolyl tetrazolium assay (MTT), transmission electron microscope, fluorescent staining, flow cytometry, western blot were used in this study. The study has demonstrated that EGCG suppressed Hcy-induced endothelial cell morphological changes and reactive oxygen species (ROS) generation. Moreover, EGCG dose-dependently prevented Hcy-induced HUVECs cytotoxicity and apoptotic biochemical changes such as reducing mitochondrial membrane potential (MMP), decreasing Bcl-2/Bax protein ratio and activating caspase-9 and 3. In addition, EGCG enhanced the protein ratio of p-Akt/Akt, endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) formation in injured cells. In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy).

Antibacterial and physical properties of EGCG-containing glass ionomer cements.

PubMed

Hu, Jieqiong; Du, Xijin; Huang, Cui; Fu, Dongjie; Ouyang, Xiaobai; Wang, Yake

2013-10-01

To evaluate the effect of the addition of epigallocatechin-3-gallate (EGCG) on the antibacterial and physical properties of glass ionomer cement (GIC). A conventional GIC, Fuji IX, was used as a control. EGCG was incorporated into GIC at 0.1% (w/w) and used as the experimental group. Chlorhexidine (CHX) was added into GIC at 1% (w/w) as a positive control. The anti-biofilm effect of the materials was assessed by a colorimetric technique (MTT assay) and scanning electron microscopy (SEM). The leaching antibacterial activity of the materials on Streptococcus mutans was evaluated by an agar-diffusion test. The flexural strength of the materials was evaluated using a universal testing machine and the surface microhardness was measured using a microhardness tester. The fluoride-releasing property of the materials was tested by ion chromatography. The optical density (OD) values of the GIC-EGCG group were significantly decreased at 4h compared with the GIC group, but only a slightly decreased tendency was observed at 24h (P>0.05). No inhibition zones were detected in the GIC group during the study period. Significant differences were found between each group (P<0.05). Compared with the control group, there was a significant increase in the flexural strength and surface microhardness for the GIC-EGCG group (P<0.05). The fluoride ion release was not influenced by EGCG-incorporation (P>0.05). These findings suggested that GIC-containing 0.1% (w/w) EGCG is a promising restorative material with improved mechanical properties and a tendency towards preferable antibacterial properties. Modification of the glass ionomer cements with EGCG to improve the antibacterial and physical properties showed some encouraging results. This suggested that the modification of GIC with EGCG might be an effective strategy to be used in the dental clinic. However, this was only an in vitro study and clinical trials would need to verify true outcomes. Copyright © 2013 Elsevier Ltd. All rights

Role of Spm-Cer-S1P signalling pathway in MMP-2 mediated U46619-induced proliferation of pulmonary artery smooth muscle cells: protective role of epigallocatechin-3-gallate.

PubMed

Chowdhury, Animesh; Sarkar, Jaganmay; Chakraborti, Tapati; Chakraborti, Sajal

2015-10-01

During remodelling of pulmonary artery, marked proliferation of pulmonary artery smooth muscle cells (PASMCs) occurs, which contributes to pulmonary hypertension. Thromboxane A2 (TxA2) has been shown to produce pulmonary hypertension. The present study investigates the inhibitory effect of epigallocatechin-3-gallate (EGCG) on the TxA2 mimetic, U46619-induced proliferation of PASMCs. U46619 at a concentration of 10 nM induces maximum proliferation of bovine PASMCs. Both pharmacological and genetic inhibitors of p(38)MAPK, NF-κB and MMP-2 significantly inhibit U46619-induced cell proliferation. EGCG markedly abrogate U46619-induced p(38)MAPK phosphorylation, NF-κB activation, proMMP-2 expression and activation, and also the cell proliferation. U46619 causes an increase in the activation of sphingomyelinase (SMase) and sphingosine kinase (SPHK) and also increase sphingosine 1 phosphate (S1P) level. U46619 also induces phosphorylation of ERK1/2, which phosphorylates SPHK leading to an increase in S1P level. Both pharmacological and genetic inhibitors of SMase and SPHK markedly inhibit U46619-induced cell proliferation. Additionally, pharmacological and genetic inhibitors of MMP-2 markedly abrogate U46619-induced SMase activity and S1P level. EGCG markedly inhibit U46619-induced SMase activity, ERK1/2 and SPHK phosphorylation and S1P level in the cells. Overall, Sphingomyeline-Ceramide-Sphingosine-1-phosphate (Spm-Cer-S1P) signalling axis plays an important role in MMP-2 mediated U46619-induced proliferation of PASMCs. Importantly, EGCG inhibits U46619 induced increase in MMP-2 activation by modulating p(38)MAPK-NFκB pathway and subsequently prevents the cell proliferation. Copyright © 2015 John Wiley & Sons, Ltd.

Urea-Driven Epigallocatechin Gallate (EGCG) Permeation into the Ferritin Cage, an Innovative Method for Fabrication of Protein-Polyphenol Co-assemblies.

PubMed

Yang, Rui; Liu, Yuqian; Meng, Demei; Chen, Zhiyu; Blanchard, Christopher L; Zhou, Zhongkai

2017-02-22

The 8 nm diameter cavity endows the ferritin cage with a natural space to encapsulate food components. In this work, urea was explored as a novel medium to facilitate the formation of ferritin-polyphenol co-assemblies. Results indicated that urea (20 mM) could expand the 4-fold channel size of apo-red bean ferritin (apoRBF) with an increased initial iron release rate υ 0 (0.22 ± 0.02 μM min -1 ) and decreased α-helix content (5.6%). Moreover, urea (20 mM) could facilitate the permeation of EGCG into the apoRBF without destroying the ferritin structure and thus form ferritin-EGCG co-assemblies (FECs) with an encapsulation ratio and loading capacity of 17.6 and 2.1% (w/w), respectively. TEM exhibited that FECs maintained a spherical morphology with a 12 nm diameter in size. Fluorescence analysis showed that urea intervention could improve the binding constant K [(1.22 ± 0.8) × 10 4 M -1 ] of EGCG to apoRBF. Furthermore, the EGCG thermal stability was significantly improved (20-60 °C) compared with free EGCG. Additionally, this urea-involved method was applicable for chlorogenic acid and anthocyanin encapsulation by the apoRBF cage. Thus, urea shows potential as a novel potential medium to encapsulate and stabilize bioactive polyphenols for food usage based on the ferritin protein cage structure.

Survivin knockdown increased anti-cancer effects of (−)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N- BE2 and SH-SY5Y cells

PubMed Central

Hossain, Md. Motarab; Banik, Naren L.; Ray, Swapan K.

2012-01-01

Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (−)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly in SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in expression of NFP, NSE, and e-cadherin and also decreases in expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-κB), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in vitro network

Y-27632 Increases Sensitivity of PANC-1 Cells to EGCG in Regulating Cell Proliferation and Migration.

PubMed

Liu, Xing; Bi, Yongyi

2016-10-03

BACKGROUND The study aimed to investigate the inhibitory effect of (1R,4r)-4-((R)-1-aminoethyl)-N-(pyridin-4-yl) cyclohexanecarboxamide (Y-27632) and (-)-epigallocatechin-3-gallate (EGCG) on the proliferation and migration of PANC-1 cells. EGCG, found in green tea, has been previously shown to be one of the most abundant and powerful catechins in cancer prevention and treatment. Y-27632, a selective inhibitor of rho-associated protein kinase 1, is widely used in treating cardiovascular disease, inflammation, and cancer. MATERIAL AND METHODS PANC-1 cells, maintained in Dulbecco's Modified Eagle's Medium, were treated with dimethyl sulfoxide (control) as well as different concentrations (20, 40, 60, and 80 μg/mL) of EGCG for 48 h. In addition, PANC-1 cells were treated separately with 60 μg/mL EGCG, 20 μM Y-27632, and EGCG combined with Y-27632 (60 μg/mL EGCG + 20 μM Y-27632) for 48 h. The effect of EGCG and Y-27632 on the proliferation and migration of PANC-1 cells was evaluated using Cell Counting Kit-8 and transwell migration assays. The expression of peroxisome proliferator-activated receptor alpha (PPARα) and Caspase-3 mRNA was determined by Quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS EGCG (20-80 μg/mL) inhibited cell viability in a dose-dependent manner. Y-27632 enhanced the sensitivity of PANC-1 cells to EGCG (by increasing the expression of PPARa and Caspase-3 mRNA) and suppressed cell proliferation. PANC-1 cell migration was inhibited by treatment with a combination of EGCG and Y-27632. CONCLUSIONS Y-27632 increases the sensitivity of PANC-1 cells to EGCG in regulating cell proliferation and migration, which is likely to be related to the expression of PPARa mRNA and Caspase-3 mRNA.

Evaluation and Development of Radiation Countermeasures at AFRRI

DTIC Science & Technology

2005-01-01

epigallocatechin gallate ( EGCG ), benzyl styryl sulfones, CpG oligonucleotides, a superoxide dismutase mi- metic, statins, dipeptidyl peptidase inhibitors, and...candidate (Hollis-Eden Pharmaceuticals) • Soy isoflavones • Vitamin E-related compounds (Yasoo Health) • Phenylacetate, phenylbutyrate, EGCG (late

EGCG evokes Nrf2 nuclear translocation and dampens PTP1B expression to ameliorate metabolic misalignment under insulin resistance condition.

PubMed

Mi, Yashi; Zhang, Wentong; Tian, Haoyu; Li, Runnan; Huang, Shuxian; Li, Xingyu; Qi, Guoyuan; Liu, Xuebo

2018-03-01

As a major nutraceutical component of green tea (-)-epigallocatechin-3-gallate (EGCG) has attracted interest from scientists due to its well-documented antioxidant and antiobesity bioactivities. In the current study, we aimed to investigate the protective effect of EGCG on metabolic misalignment and in balancing the redox status in mice liver and HepG2 cells under insulin resistance condition. Our results indicated that EGCG accelerates the glucose uptake and evokes IRS-1/Akt/GLUT2 signaling pathway via dampening the expression of protein tyrosine phosphatase 1B (PTP1B). Consistently, ectopic expression of PTP1B by Ad-PTP1B substantially impaired EGCG-elicited IRS-1/Akt/GLUT2 signaling pathway. Moreover, EGCG co-treatment stimulated nuclear translocation of Nrf2 by provoking P13K/AKT signaling pathway and thus modulated the downstream expressions of antioxidant enzymes such as HO-1 and NQO-1 in HepG2 cells. Furthermore, knockdown Nrf2 by small interfering RNA (siRNA) notably enhanced the expression of PTP1B and blunt EGCG-stimulated glucose uptake. Consistent with these results, in vivo study revealed that EGCG supplement significantly ameliorated high-fat and high-fructose diet (HFFD)-triggered insulin resistance and oxidative stress by up-regulating the IRS-1/AKT and Keap1/Nrf2 transcriptional pathways. Administration of an appropriate chemopreventive agent, such as EGCG, could potentially serve as an additional therapeutic intervention in the arsenal against obesity.

Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, Md. Motarab; Banik, Naren L.; Ray, Swapan K., E-mail: swapan.ray@uscmed.sc.edu

Neuroblastoma is a solid tumor that mostly occurs in children. Malignant neuroblastomas have poor prognosis because conventional chemotherapeutic agents are hardly effective. Survivin, which is highly expressed in some malignant neuroblastomas, plays a significant role in inhibiting differentiation and apoptosis and promoting cell proliferation, invasion, and angiogenesis. We examined consequences of survivin knockdown by survivin short hairpin RNA (shRNA) plasmid and then treatment with (-)-epigallocatechin-3-gallate (EGCG), a green tea flavonoid, in malignant neuroblastoma cells. Our Western blotting and laser scanning confocal immunofluorescence microscopy showed that survivin was highly expressed in malignant neuroblastoma SK-N-BE2 and SH-SY5Y cell lines and slightly inmore » SK-N-DZ cell line. Expression of survivin was very faint in malignant neuroblastoma IMR32 cell line. We transfected SK-N-BE2 and SH-SY-5Y cells with survivin shRNA, treated with EGCG, and confirmed knockdown of survivin at mRNA and protein levels. Survivin knockdown induced morphological features of neuronal differentiation, as we observed following in situ methylene blue staining. Combination of survivin shRNA and EGCG promoted neuronal differentiation biochemically by increases in the expression of NFP, NSE, and e-cadherin and also decreases in the expression of Notch-1, ID2, hTERT, and PCNA. Our in situ Wright staining and Annexin V-FITC/PI staining showed that combination therapy was highly effective in inducing, respectively, morphological and biochemical features of apoptosis. Apoptosis occurred with activation of caspase-8 and cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, mitochondrial release of cytochrome c, and increases in the expression and activity of calpain and caspase-3. Combination therapy decreased migration of cells through matrigel and inhibited proliferative (p-Akt and NF-{kappa}B), invasive (MMP-2 and MMP-9), and angiogenic (VEGF and b-FGF) factors. Also, in

Clinical Evaluation of a New-Formula Shampoo for Scalp Seborrheic Dermatitis Containing Extract of Rosa centifolia Petals and Epigallocatechin Gallate: A Randomized, Double-Blind, Controlled Study.

PubMed

Kim, Yu Ri; Kim, Jeong-Hwan; Shin, Hong-Ju; Choe, Yong Beom; Ahn, Kyu Joong; Lee, Yang Won

2014-12-01

Scalp seborrheic dermatitis is a chronic type of inflammatory dermatosis that is associated with sebum secretion and proliferation of Malassezia species. Ketoconazole or zinc-pyrithione shampoos are common treatments for scalp seborrheic dermatitis. However, shampoos comprising different compounds are required to provide patients with a wider range of treatment options. This study was designed to evaluate a new-formula shampoo that contains natural ingredients-including extract of Rosa centifolia petals and epigallocatechin gallate (EGCG)-that exert antioxidative, anti-inflammatory, and sebum secretion inhibitory effects, and antifungal agents for the treatment of scalp seborrheic dermatitis. Seventy-five patients were randomized into three treatment groups; new-formula shampoo, 2% ketoconazole shampoo, and 1% zinc- pyrithione shampoo. The clinical severity scores and sebum levels were assessed by the same dermatologists at baseline (week 0), and at 2 and 4 weeks after using the shampoo. User satisfaction and irritation were also assessed with the aid of a questionnaire. The efficacy of the new-formula shampoo was comparable to that of both the 1% zinc-pyrithione shampoo and the 2% ketoconazole shampoo. Furthermore, it was found to provide a more rapid response than the 1% zinc-pyrithione shampoo for mild erythema lesions and was associated with greater user satisfaction compared with the 2% ketoconazole shampoo. However, the new-formula shampoo did not exhibit the previously reported sebum inhibitory effect. Extract of R. centifolia petals or EGCG could be useful ingredients in the treatment of scalp seborrheic dermatitis.

Quantitative proteomic analysis reveals the role of tea polyphenol EGCG in egg whites in response to vanadium stress.

PubMed

Wang, Jianping; Bai, Xue; Ding, Xuemei; Bai, Shiping; Zeng, Qiufeng; Mao, Xiangbing; Zhang, Keying

Tea polyphenol (TP) epigallo-catechin-3-gallate (EGCG) can alleviate vanadium (V) stress in laying hens; however, our understanding of the molecular mechanisms and proteomic changes occurring in the egg albumen remains limited. The aim of the present study is to better understand the response in layers under V challenge and mechanism of EGCG detoxification. We divided 120 layers into four treatments in the absence and presence of 130 mg/kg EGCG, supplemented with either 0 or 5 mg/kg V. The Haugh unit (HU) was decreased and the apoptosis rate of magnum and V residual in egg was increased by the effect of vanadium and EGCG alleviated the detrimental effect in HU and apoptosis rate induced by vanadium (interactive effect, P < 0.05). In all, 379 proteins were identified and 28 differential proteins were observed with and without EGCG and V. Eight proteins, which respond to stress stimuli (five immune response proteins [F1P3B2, P21760, A2N881, F2Z4L6, and P02789], and one cell redox homeostasis protein [Q5F472] were presented in the albumen of laying hens with EGCG administration. Proteins involved in heavy metal binding (E1C5J4) and cell proliferation (F1NX05 and E1BT2) also were changed in EGCG-treated albumen. The detoxification mechanism of EGCG under V stress may act through regulating metal-binding mediation, cell proliferation, and immune function-related proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

EGCG inhibits Cd(2+)-induced apoptosis through scavenging ROS rather than chelating Cd(2+) in HL-7702 cells.

PubMed

An, Zhen; Qi, Yongmei; Huang, Dejun; Gu, Xueyan; Tian, Yihong; Li, Ping; Li, Hui; Zhang, Yingmei

2014-05-01

Epigallocatechin-3-gallat (EGCG), the major catechin in green tea, shows a potential protective effect against heavy metal toxicity to humans. Apoptosis is one of the key events in cadmium (Cd(2+))-induced cytotoxicity. Nevertheless, the study of EGCG on Cd(2+)-induced apoptosis is rarely reported. The objective of this study was to clarify the effect and detailed mechanism of EGCG on Cd(2+)-induced apoptosis. Normal human liver cells (HL-7702) were treated with Cd(2+) for 21 h, and then co-treated with EGCG for 3 h. Cell viability, apoptosis, intracellular reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (MMP) and caspase-3 activity were detected. On the other hand, the chelation of Cd(2+) with EGCG was tested by UV-Vis spectroscopy analysis and Nuclear Magnetic Resonance ((1)H NMR) spectroscopy under neutral condition (pH 7.2). Cd(2+) significantly decreased the cell viability and induced apoptosis in HL-7702 cells. Conversely, EGCG co-treatment resulted in significant inhibition of Cd(2+)-induced reduction of cell viability and apoptosis, implying a rescue effect of EGCG against Cd(2+) poisoning. The protective effect most likely arises from scavenging ROS and maintaining redox homeostasis, as the generation of intracellular ROS and MDA is significantly reduced by EGCG, which further prevents MMP collapse and suppresses caspase-3 activity. However, no evidence is observed for the chelation of EGCG with Cd(2+) under neutral condition. Therefore, a clear conclusion from this work can be made that EGCG could inhibit Cd(2+)-induced apoptosis by acting as a ROS scavenger rather than a metal chelating agent.

Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils.

PubMed

Lee, Hyung; Bae, Jae Hoon; Lee, Seong-Ryong

2004-09-15

Previous studies have demonstrated that a green tea polyphenol, (-)-epigallocatechine gallate (EGCG), has a potent free radical scavenging and antioxidant effect. Glutamate leads to excitotoxicity and oxidative stress, which are important pathophysiologic responses to cerebral ischemia resulting in brain edema and neuronal damage. We investigated the effect of EGCG on excitotoxic neuronal damage in a culture system and the effect on brain edema formation and lesion after unilateral cerebral ischemia in gerbils. In vitro, excitotoxicity was induced by 24-hr incubation with N-methyl-D-aspartate (NMDA; 10 microM), AMPA (10 microM), or kainate (20 microM). EGCG (5 microM) was added to the culture media alone or with excitotoxins. We examined malondialdehyde (MDA) level and neuronal viability to evaluate the effect of EGCG. In vivo, unilateral cerebral ischemia was induced by occlusion of the right common carotid artery for 30, 60, or 90 min and followed by reperfusion of 24 hr. Brain edema, MDA, and infarction were examined to evaluate the protective effect of EGCG. EGCG (25 or 50 mg/kg, intraperitoneally) was administered twice, at 30 min before and immediately after ischemia. EGCG reduced excitotoxin-induced MDA production and neuronal damage in the culture system. In the in vivo study, treatment of gerbils with the lower EGCG dose failed to show neuroprotective effects; however, the higher EGCG dose attenuated the increase in MDA level caused by cerebral ischemia. EGCG also reduced the formation of postischemic brain edema and infarct volume. These results demonstrate EGCG may have future possibilities as a neuroprotective agent against excitotoxicity-related neurologic disorders such as brain ischemia.

[Isolation and purification of seven catechin compounds from fresh tea leaves by semi-preparative liquid chromatography].

PubMed

Gong, Zhihong; Chen, Si; Gao, Jiangtao; Li, Meihong; Wang, Xiaxia; Lin, Jun; Yu, Xiaomin

2017-11-08

An effective and simple method was established to simultaneously purify seven tea catechins (gallocatechin (GC), epigallocatechin (EGC), catechin (C), epigallocatechin-3- O -gallate (EGCG), epicatechin (EC), epigallocatechin-3- O -(3- O -methyl)-gallate (EGCG3"Me) and epicatechin-3- O -gallate (ECG)) from fresh tea leaves by semi-preparative high performance liquid chromatography (HPLC). Fresh leaves of Tieguanyin tea were successively extracted with methanol and chloroform. Then crude catechins were precipitated from the aqueous fraction of chloroform extraction by adding lead subacetate. Crude catechins were used for the isolation of the seven target catechin compounds by semi-preparative HPLC. Methanol-water and acetonitrile-water were sequentially used as mobile phases. After two rounds of semi-preparative HPLC, all target compounds were achieved with high purities (>90%). The proposed method was tested on two additional tea cultivars and showed similar results. This method demonstrated a simple and efficient strategy based on solvent extraction, ion precipitation and semi-preparative HPLC for the preparation of multiple catechins from tea leaves.

Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer

DTIC Science & Technology

2011-05-01

of EGCG : 457/168.9; • m/z transitions of ethyl gallate (internal standard): 168.9/124.9 Page 8 (A...with green tea polyphenol epigallocatechin -3- gallate . Cancer Res 2009; 69:1712-6. PMID: 19223530 3. Perez C, Sanchez A, Putnam D, Ting D, Langer R...We developed an HPLC method to determine the amount of EGCG encapsulated in the nanoparticles. HPLC analysis showed that chitosan nanoparticles can

Low dose EGCG treatment beginning in adolescence does not improve cognitive impairment in a Down syndrome mouse model.

PubMed

Stringer, Megan; Abeysekera, Irushi; Dria, Karl J; Roper, Randall J; Goodlett, Charles R

2015-11-01

Down syndrome (DS) or Trisomy 21 causes intellectual disabilities in humans and the Ts65Dn DS mouse model is deficient in learning and memory tasks. DYRK1A is triplicated in DS and Ts65Dn mice. Ts65Dn mice were given up to ~20mg/kg/day epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, or water beginning on postnatal day 24 and continuing for three or seven weeks, and were tested on a series of behavioral and learning tasks, including a novel balance beam test. Ts65Dn as compared to control mice exhibited higher locomotor activity, impaired novel object recognition, impaired balance beam and decreased spatial learning and memory. Neither EGCG treatment improved performance of the Ts65Dn mice on these tasks. Ts65Dn mice had a non-significant increase in Dyrk1a activity in the hippocampus and cerebellum. Given the translational value of the Ts65Dn mouse model, further studies will be needed to identify the EGCG doses (and mechanisms) that may improve cognitive function. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel convenient process to obtain a raw decaffeinated tea polyphenol fraction using a lignocellulose column.

PubMed

Sakanaka, Senji

2003-05-07

Lignocellulose prepared from sawdust was investigated for its potential application in obtaining a raw decaffeinated tea polyphenol fraction from tea extract. Tea polyphenols having gallate residues, namely, (-)epigallocatechin gallate (EGCg) and (-)epicatechin gallate (ECg), were adsorbed on the lignocellulose column, while caffeine was passed through it. Adsorbed polyphenols were eluted with 60% ethanol, and the elute was found to consist mainly of EGCg and ECg. The caffeine/EGCg ratio was 0.696 before lignocellulose column treatment, but it became 0.004 after the column treatment. These results suggest that the lignocellulose column provides a useful and convenient process of purification of tea polyphenol fraction accompanied by decaffeination.

Encapsulated nanoepigallocatechin-3-gallate and elemental selenium nanoparticles as paradigms for nanochemoprevention.

PubMed

Wang, Dongxu; Taylor, Ethan Will; Wang, Yijun; Wan, Xiaochun; Zhang, Jinsong

2012-01-01

Chemoprevention that impedes one or more steps in carcinogenesis, via long-term administration of naturally occurring or synthetic compounds, is widely considered to be a crucial strategy for cancer control. Selenium (Se) has chemopreventive effects, but its application is limited due to a low therapeutic index as shown in numerous animal experiments. In contrast to Se, which was known for its toxicity prior to the discovery of its beneficial effects, the natural compound epigallocatechin-3-gallate (EGCG) was originally considered to be nontoxic. Due to its preventive effects on many types of cancer in various animal models, EGCG has been regarded as a prime example of a promising chemopreventive agent without major toxicity concerns. However, very recently, evidence has accumulated showing that efficacious doses of EGCG used in health promotion may not be far from its toxic dose level. Therefore, both Se and EGCG need to be modified by novel pharmaceutical technologies to attain enhanced efficacy and/or reduced toxicity. Nanotechnology may be one of these technologies. In support of this hypothesis, the characteristics of polylactic acid and polyethylene glycol-encapsulated nano-EGCG and elemental Se nanoparticles dispersed by bovine serum albumin are reviewed in this article. Encapsulation of EGCG to form nano-EGCG leads to its enhanced stability in plasma and remarkably superior chemopreventive effects, with more than tenfold dose advantages in inducing apoptosis and inhibition of both angiogenesis and tumor growth. Se at nanoparticle size ("Nano-Se"), compared with Se compounds commonly used in dietary supplements, has significantly lower toxicity, without compromising its ability to upregulate selenoenzymes at nutritional levels and induce phase II enzymes at supranutritional levels.

Encapsulated nanoepigallocatechin-3-gallate and elemental selenium nanoparticles as paradigms for nanochemoprevention

PubMed Central

Wang, Dongxu; Taylor, Ethan Will; Wang, Yijun; Wan, Xiaochun; Zhang, Jinsong

2012-01-01

Chemoprevention that impedes one or more steps in carcinogenesis, via long-term administration of naturally occurring or synthetic compounds, is widely considered to be a crucial strategy for cancer control. Selenium (Se) has chemopreventive effects, but its application is limited due to a low therapeutic index as shown in numerous animal experiments. In contrast to Se, which was known for its toxicity prior to the discovery of its beneficial effects, the natural compound epigallocatechin-3-gallate (EGCG) was originally considered to be nontoxic. Due to its preventive effects on many types of cancer in various animal models, EGCG has been regarded as a prime example of a promising chemopreventive agent without major toxicity concerns. However, very recently, evidence has accumulated showing that efficacious doses of EGCG used in health promotion may not be far from its toxic dose level. Therefore, both Se and EGCG need to be modified by novel pharmaceutical technologies to attain enhanced efficacy and/or reduced toxicity. Nanotechnology may be one of these technologies. In support of this hypothesis, the characteristics of polylactic acid and polyethylene glycol-encapsulated nano-EGCG and elemental Se nanoparticles dispersed by bovine serum albumin are reviewed in this article. Encapsulation of EGCG to form nano-EGCG leads to its enhanced stability in plasma and remarkably superior chemopreventive effects, with more than tenfold dose advantages in inducing apoptosis and inhibition of both angiogenesis and tumor growth. Se at nanoparticle size (“Nano-Se”), compared with Se compounds commonly used in dietary supplements, has significantly lower toxicity, without compromising its ability to upregulate selenoenzymes at nutritional levels and induce phase II enzymes at supranutritional levels. PMID:22619522

Preventive effects of C-2 epimeric isomers of tea catechins on mouse type I allergy.

PubMed

Yoshino, Kyoji; Miyase, Toshio; Sano, Mitsuaki

2010-01-01

The preventive effects of C-2 epimeric isomers of (-)-epigallocatechin-3-O-gallate (EGCG) and the O-methylated derivative, (-)-epigallocatechin-3-O-(3-O-methyl)gallate (EGCG3''Me), against ovalbumin-induced type I allergy in male mice were investigated. EGCG and EGCG3''Me exhibited strong antiallergic effects by oral administration at doses of 25 and 50 mg/kg body weight. The antiallergic effects of their C-2 epimers, (-)-gallocatechin-3-O-gallate and (-)-gallocatechin-3-O-(3-O-methyl)gallate (GCG3''Me), on mouse type I allergy were almost equivalent to and/or as strong as those of the corresponding original catechins, respectively. Oral administration of these compounds at a dose of 50 mg/kg body weight tended to suppress the increases in interleukin-4 levels in the abdominal walls of allergic mice and immunoglobulin E levels in the serum of allergic mice. In particular, the administration of GCG3''Me exhibited significant effects on the production and/or release of these parameters stimulating type 2 T helper cells and mast cells in the type I allergic process. These results indicated that C-2 epimerization of tea catechins, which are produced during heat processing at high temperatures, would not be disadvantageous for preventive effects on type I allergy.

Better Management of Alcohol Liver Disease Using a ‘Microstructured Synbox’ System Comprising L. plantarum and EGCG

PubMed Central

Rishi, Praveen; Arora, Sumeha; Kaur, Ujjwal Jit; Chopra, Kanwaljit; Kaur, Indu Pal

2017-01-01

Synergistic combination of probiotics with carbohydrate based prebiotics is widely employed for the treatment of various gut related disorders. However, such carbohydrate based prebiotics encourage the growth of pathogens and probiotics, equally. Aim of the study was (i) to explore the possibility of using epigallocatechin gallate (EGCG) a phenolic compound, as a prebiotic for L.plantarum; (ii) to develop and evaluate a microstructured synbox (microencapsulating both probiotic and EGCG together) in rat model of alcohol liver disease (ALD); and, (iii) to confirm whether the combination can address issues of EGCG bioavailability and probiotic survivability in adverse gut conditions. Growth enhancing effect of EGCG on L. plantarum (12.8±0.5 log 10 units) was significantly (p≤0.05) better than inulin (11.4±0.38 log 10 units), a natural storage carbohydrate. The formulated synbox significantly modulated the levels of alcohol, endotoxin, hepatic enzymes and restored the hepatoarchitecture in comparison to simultaneous administration of free agents. Additionally, using a battery of techniques, levels of various cellular and molecular markers viz. NF-kB/p50, TNF-α, IL12/p40, and signalling molecules TLR4, CD14, MD2, MyD88 and COX-2 were observed to be suppressed. Developed microbead synbox, as a single delivery system for both the agents showed synergism and hence, holds promise as a therapeutic option for ALD management. PMID:28060832

Clinical Evaluation of a New-Formula Shampoo for Scalp Seborrheic Dermatitis Containing Extract of Rosa centifolia Petals and Epigallocatechin Gallate: A Randomized, Double-Blind, Controlled Study

PubMed Central

Kim, Yu Ri; Kim, Jeong-Hwan; Shin, Hong-Ju; Choe, Yong Beom; Ahn, Kyu Joong

2014-01-01

Background Scalp seborrheic dermatitis is a chronic type of inflammatory dermatosis that is associated with sebum secretion and proliferation of Malassezia species. Ketoconazole or zinc-pyrithione shampoos are common treatments for scalp seborrheic dermatitis. However, shampoos comprising different compounds are required to provide patients with a wider range of treatment options. Objective This study was designed to evaluate a new-formula shampoo that contains natural ingredients-including extract of Rosa centifolia petals and epigallocatechin gallate (EGCG)-that exert antioxidative, anti-inflammatory, and sebum secretion inhibitory effects, and antifungal agents for the treatment of scalp seborrheic dermatitis. Methods Seventy-five patients were randomized into three treatment groups; new-formula shampoo, 2% ketoconazole shampoo, and 1% zinc- pyrithione shampoo. The clinical severity scores and sebum levels were assessed by the same dermatologists at baseline (week 0), and at 2 and 4 weeks after using the shampoo. User satisfaction and irritation were also assessed with the aid of a questionnaire. Results The efficacy of the new-formula shampoo was comparable to that of both the 1% zinc-pyrithione shampoo and the 2% ketoconazole shampoo. Furthermore, it was found to provide a more rapid response than the 1% zinc-pyrithione shampoo for mild erythema lesions and was associated with greater user satisfaction compared with the 2% ketoconazole shampoo. However, the new-formula shampoo did not exhibit the previously reported sebum inhibitory effect. Conclusion Extract of R. centifolia petals or EGCG could be useful ingredients in the treatment of scalp seborrheic dermatitis. PMID:25473226

Interactions of quercetin, curcumin, epigallocatechin gallate and folic acid with gelatin.

PubMed

Yang, Tingting; Yang, Huiru; Fan, Yan; Li, Bafang; Hou, Hu

2018-06-15

Some small bioactive molecules from food show the potential health benefits, but with poor chemical stability and bioavailability. The interactions between small molecules and gelatin were investigated. Fluorescence experiments demonstrated that the bimolecular quenching constants (k q ) of complexes (gelatin-quercetin, gelatin-curcumin, gelatin-epigallocatechin gallate, gelatin-folic acid) were 3.7 × 10 12  L·mol -1 ·s -1 , 1.4 × 10 12  L·mol -1 ·s -1 , 2.7 × 10 12  L·mol -1 ·s -1 and 8.5 × 10 12  L·mol -1 ·s -1 , indicating that fluorescence quenching did not arise from a dynamical mechanism, but from gelatin-small molecules binding. Furthermore, the affinity with gelatin was ranked in the order of folic acid > quercetin > epigallocatechin gallate > curcumin. Fluorescence spectroscopy, ultraviolet and visible absorption spectroscopy, FTIR and circular dichroism showed that the interactions between small molecules and gelatin did not significantly alter the conformation and secondary structure of gelatin. Non-covalent interactions may result in the binding of gelatin with small molecules. The interactions were considered to be through two modes: (1) small molecules bound within the hydrophobic pockets of gelatin; (2) small molecules surrounded the gelatin molecule mainly through hydrogen bonds and hydrophobic interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

PubMed Central

Fang, Chih-Yeu; Wu, Chung-Chun; Hsu, Hui-Yu; Chuang, Hsin-Ying; Huang, Sheng-Yen; Tsai, Ching-Hwa; Chang, Yao; Tsao, George Sai-Wah; Chen, Chi-Long; Chen, Jen-Yang

2015-01-01

(−)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC), yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK) phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC. PMID:25625511

Metabolic phenotyping of various tea (Camellia sinensis L.) cultivars and understanding of their intrinsic metabolism.

PubMed

Ji, Hyang-Gi; Lee, Yeong-Ran; Lee, Min-Seuk; Hwang, Kyeong Hwan; Kim, Eun-Hee; Park, Jun Seong; Hong, Young-Shick

2017-10-15

Recently, we selected three tea (Camellia sinensis) cultivars that are rich in taste, epigallocatechin-3-O-gallate (EGCG) and epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3″Me) and then cultivated them through asexual propagation by cutting in the same region. In the present study, proton nuclear magnetic resonance ( 1 H NMR)-based metabolomics was applied to characterize the metabotype and to understand the metabolic mechanism of these tea cultivars including wild type tea. Of the tea leaf metabolite variations, reverse associations of amino acid metabolism with catechin compound metabolism were found in the rich-taste, and EGCG- and EGCG3″Me-rich tea cultivars. Indeed, the metabolism of individual catechin compounds in the EGCG3″Me-rich cultivar differed from those of other tea cultivars. The current study highlights the distinct metabolism of various tea cultivars newly selected for cultivation and the important role of metabolomics in understanding the metabolic mechanism. Thus, comprehensive metabotyping is a useful method to assess and then develop a new plant cultivar. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polyphenols and Prostate Cancer Chemoprevention

DTIC Science & Technology

2004-03-01

The polyphenols, catechin, (-)- epigallocatechin -3- gallate ( EGCG ), genistein and resveratrol, are associated with reduced incidences of prostate and...protective effect without adverse effects with possible elevated exposure. The specific aims are 1) to investigate the potential of genistein, EGCG and...genistein, EGCG and resveratrol to regulate sex steroid- and specific growth factor-receptor and ligand expression as mechanism of prostate cancer

Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (–)-epigallocatechin-3-gallate

PubMed Central

He, Yan; Cui, Jiankun; Lee, James C-M; Ding, Shinghua; Chalimoniuk, Malgorzata; Simonyi, Agnes; Sun, Albert Y; Gu, Zezong; Weisman∥, Gary A; Gibson Wood, W; Sun, Grace Y

2011-01-01

Excessive production of Aβ (amyloid β-peptide) has been shown to play an important role in the pathogenesis of AD (Alzheimer's disease). Although not yet well understood, aggregation of Aβ is known to cause toxicity to neurons. Our recent study demonstrated the ability for oligomeric Aβ to stimulate the production of ROS (reactive oxygen species) in neurons through an NMDA (N-methyl-d-aspartate)-dependent pathway. However, whether prolonged exposure of neurons to aggregated Aβ is associated with impairment of NMDA receptor function has not been extensively investigated. In the present study, we show that prolonged exposure of primary cortical neurons to Aβ oligomers caused mitochondrial dysfunction, an attenuation of NMDA receptor-mediated Ca2+ influx and inhibition of NMDA-induced AA (arachidonic acid) release. Mitochondrial dysfunction and the decrease in NMDA receptor activity due to oligomeric Aβ are associated with an increase in ROS production. Gp91ds-tat, a specific peptide inhibitor of NADPH oxidase, and Mn(III)-tetrakis(4-benzoic acid)-porphyrin chloride, an ROS scavenger, effectively abrogated Aβ-induced ROS production. Furthermore, Aβ-induced mitochondrial dysfunction, impairment of NMDA Ca2+ influx and ROS production were prevented by pre-treatment of neurons with EGCG [(−)-epigallocatechin-3-gallate], a major polyphenolic component of green tea. Taken together, these results support a role for NADPH oxidase-mediated ROS production in the cytotoxic effects of Aβ, and demonstrate the therapeutic potential of EGCG and other dietary polyphenols in delaying onset or retarding the progression of AD. PMID:21434871

Combination of erlotinib and EGCG induces apoptosis of head and neck cancers through posttranscriptional regulation of Bim and Bcl-2.

PubMed

Haque, Abedul; Rahman, Mohammad Aminur; Chen, Zhuo Georgia; Saba, Nabil F; Khuri, Fadlo R; Shin, Dong M; Ruhul Amin, A R M

2015-07-01

Combinatorial approaches using two or more compounds are gaining increasing attention for cancer therapy. We have previously reported that the combination of the EGFR-TKI erlotinib and epigallocatechin-3-gallate (EGCG) exhibited synergistic chemopreventive effects in head and neck cancers by inducing the expression of Bim, p21, p27, and by inhibiting the phosphorylation of ERK and AKT and expression of Bcl-2. In the current study, we further investigated the mechanism of regulation of Bim, Bcl-2, p21 and p27, and their role in apoptosis. shRNA-mediated silencing of Bim significantly inhibited apoptosis induced by the combination of erlotinib and EGCG (p = 0.005). On the other hand, overexpression of Bcl-2 markedly protected cells from apoptosis (p = 0.003), whereas overexpression of constitutively active AKT only minimally protected cells from apoptosis induced by the combination of the two compounds. Analysis of mRNA expression by RT-PCR revealed that erlotinib, EGCG and their combination had no significant effects on the mRNA expression of Bim, p21, p27 or Bcl-2 suggesting the post-transcriptional regulation of these molecules. Furthermore, we found that erlotinib or the combination of EGCG and erlotinib inhibited the phosphorylation of Bim and stabilized Bim after inhibition of protein translation by cycloheximide. Taken together, our results strongly suggest that the combination of erlotinib and EGCG induces apoptosis of SCCHN cells by regulating Bim and Bcl-2 at the posttranscriptional level.