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Yuanyuan Jia,1 Qiuyu Mao,1 Jingyi Yang,1 Na Du,1 Yuan Zhu,2 Wei Min1 1First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 2First People’s Hospital of Changshu City, Changshu Hospital Affiliated of Soochow University, Changshu, Jiangsu Province, People’s Republic of ChinaCorrespondence: Wei Min, Email weimin@suda.edu.cnBackground: Ultraviolet (UV) is a common stressor of skin and repeated UVA radiation contributes to photoaging. (–)-Epigallocatechin-3-Gallate (EGCG), as the major polyphenol that is found in green tea, and catechins and have shown considerable antioxidant capacity.Purpose: Our study aims to explore the effects of EGCG on UVA-induced skin photoaging process and associated mechanisms.Methods: In this study, human skin fibroblasts (HSFs) were treated with UVA and EGCG, and subsequent changes in cell morphology, telomeres, antioxidant capacity, cell cycle, and related genes were evaluated to examine the role and mechanisms of EGCG in delaying skin photoaging.Results: HSF exposed to UVA underwent an increase in aging-related biomarkers and telomere shortening. Also, UVA radiation inhibited the secretion of transforming growth factor-beta1 (TGF-β 1), induced cell cycle arrest, down-regulated antioxidant enzymes, and promoted the accumulation of oxidative product malondialdehyde (MDA) to cause further damage to cells. Increased expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase-1 (TIMP-1), p66 at mRNA levels were also observed after UVA irradiation. EGCG treatment effectively inhibited above damage processes caused by UVA radiation in HSF.Conclusion: Our study indicated that the potential mechanism of EGCG retarding photoaging is closely related to its powerful antioxidant effects and the ability to regulate the expression of related genes, and the usage of EGCG will be a potential strategy in preventing skin photoaging induced by UVA radiation.Keywords: ultraviolet A, human skin fibroblasts, (–)-Epigallocatechin-3-Gallate, EGCG, photoaging

In spite of the development of numerous vaccines for the prevention of COVID-19 and the approval of several drugs for its treatment, there is still a great need for effective and inexpensive therapies against this disease. Previously, we showed that green tea and tea catechins interfere with coronavirus replication as well as coronavirus 3CL protease activity, and also showed lower COVID-19 morbidity and mortality in countries with higher green tea consumption. However, it is not clear whether green tea is still effective against the newer SARS-CoV-2 variants including omicron. It is also not known whether higher green tea consumption continues to contribute to lower COVID-19 morbidity and mortality now that vaccination rates in many countries are high. Here, we attempted to update the information regarding green tea in relation to COVID-19. Using pharmacological and ecological approaches, we found that EGCG as well as green tea inhibit the activity of the omicron variant 3CL protease efficiently, and there continues to be pronounced differences in COVID-19 morbidity and mortality between groups of countries with high and low green tea consumption as of December 6, 2022. These results collectively suggest that green tea continues to be effective against COVID-19 despite the new omicron variants and increased vaccination. [ABSTRACT FROM AUTHOR]

Sixty-three men (15–35 years of age) regularly training in Danish gyms and supplement users were interviewed about the use of supplemental protein and food supplements, intake of caffeine- and (-)-epigallocathechin-3-gallate (EGCG)-containing supplements and beverages and any experienced adverse effects. Protein powder (60%), fish oil (54%) and multivitamin/mineral supplements (41%) were the most popular products. The daily supplementary protein intake (mean 0.42 g/kg body weight, users only) in adult men contributed substantially to their protein intake and exceeded the recommended allowance (0.83 g/kg body weight) for six adult participants (14%). Thirty-eight percent of the adult men exceeded the daily caffeine intake presumed to be safe (400 mg) with coffee as the main contributor. Thirty percent drank green tea and among this percentage, two participants had an extreme daily intake (1.5 and 2 -L). EGCG intake could not be estimated from the food supplements due to the lack of label information. Eighteen participants (29%) reported having experienced adverse effects but seventeen did not consult a physician or report the adverse effect to the Danish food authority. The most common adverse effects were insomnia, shaking, headache and palpitations, itching of the skin and stinging. Pre-workout products accounted for 53% of the adverse effects. Three adverse effects came after intake of two brands of supplements known to have contained substances such as 1,3-dimethylamine or derivatives of phenylethylamines previously having caused serious adverse effects. [ABSTRACT FROM AUTHOR]

Stroke remains one of the leading reasons of mortality and physical disability worldwide. The treatment of cerebral ischemic stroke faces challenges, partly due to a lack of effective treatments. In this study, we demonstrated that autophagy was stimulated by transient middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R). Treatment with (-)-epigallocatechin-3-gallate (EGCG), a bioactive ingredient in green tea, was able to mitigate cerebral ischemia/reperfusion injury (CIRI), given the evidence that EGCG administration could reduce the infarct volume and protect poststroke neuronal loss in MCAO/R mice in vivo and attenuate cell loss in OGD/R-challenged HT22 cells in vitro through suppressing autophagy activity. Mechanistically, EGCG inhibited autophagy via modulating the AKT/AMPK/mTOR phosphorylation pathway both in vivo and in vitro models of stroke, which was further confirmed by the results that the administration of GSK690693, an AKT/AMPK inhibitor, and rapamycin, an inhibitor of mTOR, reversed aforementioned changes in autophagy and AKT/AMPK/mTOR signaling pathway. Overall, the application of EGCG relieved CIRI by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway. [ABSTRACT FROM AUTHOR]

In spite of the development of numerous vaccines for the prevention of COVID-19 and the approval of several drugs for its treatment, there is still a great need for effective and inexpensive therapies against this disease. Previously, we showed that green tea and tea catechins interfere with coronavirus replication as well as coronavirus 3CL protease activity, and also showed lower COVID-19 morbidity and mortality in countries with higher green tea consumption. However, it is not clear whether green tea is still effective against the newer SARS-CoV-2 variants including omicron. It is also not known whether higher green tea consumption continues to contribute to lower COVID-19 morbidity and mortality now that vaccination rates in many countries are high. Here, we attempted to update the information regarding green tea in relation to COVID-19. Using pharmacological and ecological approaches, we found that EGCG as well as green tea inhibit the activity of the omicron variant 3CL protease efficiently, and there continues to be pronounced differences in COVID-19 morbidity and mortality between groups of countries with high and low green tea consumption as of December 6, 2022. These results collectively suggest that green tea continues to be effective against COVID-19 despite the new omicron variants and increased vaccination.

The survival of motor neurons (MNs) is the key to recovery of the motor function after brachial plexus root avulsion (BPRA). (-)-epigallocatechin-3-gallate (EGCG) exerts neuroprotective roles in neurons under different pathological conditions. However, the role of EGCG in regulating motor neurons under BPRA remains to be unclear. In the present study, we investigated the functional role of EGCG both in vitro and in vivo . In an in vitro study, we observed that EGCG obviously increased the cell survival rate of MNs and FIG4 protein levels compared with the vehicle control, with a peak level observed at 50 µM; EGCG can also upregulate FIG4 to reduce the cell death of MNs and increase the neurite outgrowth under oxidative stress; moreover, EGCG can upregulate FIG4 to promote the functional recovery and the survival of MNs in the ventral horn in mice after BPRA. These combined results may lay the foundation for EGCG to be a novel strategy for the treatment of BPRA.

Sixty-three men (15–35 years of age) regularly training in Danish gyms and supplement users were interviewed about the use of supplemental protein and food supplements, intake of caffeine- and (-)-epigallocathechin-3-gallate (EGCG)-containing supplements and beverages and any experienced adverse effects. Protein powder (60%), fish oil (54%) and multivitamin/mineral supplements (41%) were the most popular products. The daily supplementary protein intake (mean 0.42 g/kg body weight, users only) in adult men contributed substantially to their protein intake and exceeded the recommended allowance (0.83 g/kg body weight) for six adult participants (14%). Thirty-eight percent of the adult men exceeded the daily caffeine intake presumed to be safe (400 mg) with coffee as the main contributor. Thirty percent drank green tea and among this percentage, two participants had an extreme daily intake (1.5 and 2 -L). EGCG intake could not be estimated from the food supplements due to the lack of label information. Eighteen participants (29%) reported having experienced adverse effects but seventeen did not consult a physician or report the adverse effect to the Danish food authority. The most common adverse effects were insomnia, shaking, headache and palpitations, itching of the skin and stinging. Pre-workout products accounted for 53% of the adverse effects. Three adverse effects came after intake of two brands of supplements known to have contained substances such as 1,3-dimethylamine or derivatives of phenylethylamines previously having caused serious adverse effects.

The circadian clock is vital in the management of our daily physiological as well as metabolic processes. Disturbances of the clock can cause degenerative and age-related diseases. Increasing evidence has indicated that the intervertebral discs contain an internal biological clock related to degeneration. However, to date, no bioactive compounds have been found that can ameliorate intervertebral disc degeneration (IDD) by restoring the circadian clock. (-)-Epigallocatechin-3-gallate (EGCG) is a nutritious food with powerful antioxidant properties, as well as entraining biological clock to improve health. The purpose of this study was to determine whether the protective effects of EGCG on nucleus pulposus (NPCs) under oxidative stress is related to the circadian clock. First, we found that EGCG attenuated H2O2-induced extracellular matrix degradation in NPCs and inhibited H2O2-induced NPC apoptosis. Our in vivo experiments also confirmed this finding. Furthermore, EGCG attenuated H2O2-triggered dampening of phase shifts and daily oscillations in circadian clock gene transcription as well as protein expression levels. Intriguingly, core clock gene (Bmal1) knockdown notably blocked the protective effects of EGCG. To our knowledge, this study provides the first convincing evidence that EGCG prevents IDD in a Bmal1-dependent manner. In general, EGCG supplementation can be used as a nutritional prevention strategy for the rehabilitation of degenerative diseases related to the circadian clock. [ABSTRACT FROM AUTHOR]

The circadian clock is vital in the management of our daily physiological as well as metabolic processes. Disturbances of the clock can cause degenerative and age-related diseases. Increasing evidence has indicated that the intervertebral discs contain an internal biological clock related to degeneration. However, to date, no bioactive compounds have been found that can ameliorate intervertebral disc degeneration (IDD) by restoring the circadian clock. (-)-Epigallocatechin-3-gallate (EGCG) is a nutritious food with powerful antioxidant properties, as well as entraining biological clock to improve health. The purpose of this study was to determine whether the protective effects of EGCG on nucleus pulposus (NPCs) under oxidative stress is related to the circadian clock. First, we found that EGCG attenuated H2O2-induced extracellular matrix degradation in NPCs and inhibited H2O2-induced NPC apoptosis. Our in vivo experiments also confirmed this finding. Furthermore, EGCG attenuated H2O2-triggered dampening of phase shifts and daily oscillations in circadian clock gene transcription as well as protein expression levels. Intriguingly, core clock gene (Bmal1) knockdown notably blocked the protective effects of EGCG. To our knowledge, this study provides the first convincing evidence that EGCG prevents IDD in a Bmal1-dependent manner. In general, EGCG supplementation can be used as a nutritional prevention strategy for the rehabilitation of degenerative diseases related to the circadian clock.

Sabrina Bimonte,1,* Marco Cascella,1,* Vincenzo Schiavone,2 Farrokh Mehrabi-Kermani,3 Arturo Cuomo1 1Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS – “Fondazione G. Pascale”, Naples, Italy; 2Division of Anesthesia and Intensive Care, Hospital “Pineta Grande”, Castel Volturno, Caserta, Italy; 3Division of Neurosurgery, Hospital “Pineta Grande”, Castel Volturno, Caserta, Italy *These authors contributed equally to this work Abstract: Neuropathic pain (NP) is a complex and chronic disease caused by lesions or defects of the somatosensory nervous system. The treatments normally used for managing NP usually lack efficacy. Several animal models of NP have been engineered in order to understand the molecular mechanisms underlying NP and to find alternative molecules to use as new therapeutic agents. Preclinical in vivo studies identified the epigallocatechin-3-gallate (EGCG), a main active component of green tea (Camellia sinensis), as a possible therapeutic molecule for NP treatment due to its anti-inflammatory and antioxidant properties. Interestingly, it has been shown that EGCG reduced bone cancer pain. The purpose of this article is to discuss the potential use of EGCG for control and treatment of NP, by reviewing the preclinical studies reported in the literature and by shedding light on the potential schemes based on EGCG’s application in clinical practices. Keywords: epigallocatechin-3-gallate, EGCG, natural compound, neuropathic pain, animal models of neuropathic pain, cancer bone pain

Background/Aims: Exposure to arsenic in individuals has been found to be associated with various health-related problems including skin lesions, cancer, and cardiovascular and immunological disorders. (-)-Epigallocatechin-3-gallate (EGCG), the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, anti-apoptotic and anti-inflammatory activity in vivo and in vitro. Thus, the present study was conducted to investigate the protective effects of EGCG against arsenic-induced inflammation and immunotoxicity in mice. Methods: Serum IL-1β, IL-6 and TNF-α were determined by ELISA, tissue catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), nitric oxide and caspase 3 by commercial kits, mitochondrial membrane potential with Rh 123, mitochondrial ROS with 2’,7’-dichlorofluorescin diacetate (DCFH-DA), apoptotic and necrotic cells and T-cell phenotyping with Flow cytometry analysis. Results: The results showed that arsenic treatment significantly increased oxidative stress levels (as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione and reactive oxygen species), increased levels of inflammatory cytokines and promoted apoptosis. Arsenic exposure increased the relative frequency of the CD8+(Tc) cell subpopulation (from 2.8 to 18.9%) and decreased the frequency of CD4+(Th) cells (from 5.2 to 2.7%). Arsenic exposure also significantly decreased the frequency of T(CD3) (from 32.5% to 19.2%) and B(CD19) cells (from 55.1 to 32.5%). All of these effects induced by NaAsO2 were attenuated by EGCG. Conclusions: The present in vitro findings indicate that EGCG attenuates not only NaAsO2-induced immunosuppression but also inflammation and apoptosis.

A novel waterborne polyurethane (PU), based on (-)-epigallocatechin-3-gallate (EGCG) that contains phenolic hydroxyl group, was successfully synthesized and characterized. The structural study of PU based on EGCG through FT-IR confirmed the incorporation of EGCG into the chain of PU. The results of X-ray diffraction (XRD) showed that the introduction of EGCG changed the crystallization behavior of the pure waterborne PU. Thermogravimetric analysis (TGA) results indicated that the PU samples exhibited improved thermal decomposition temperature. The degree of phase segregation of modified PU was confirmed by Scanning electron microscope (SEM) analysis. The physical and biodegradable properties of modified PU indicated a comprehensive performance. [ABSTRACT FROM AUTHOR]

Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance the osteogenic differentiation of murine bone marrow mesenchymal stem cells and inhibit the osteoclastogenesis in RAW264.7 cells by modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) (RANK/RANKL/OPG) pathway. Our previous study also found that EGCG can promote bone defect healing in the distal femur partially via bone morphogenetic protein-2 (BMP-2). Considering the osteoinduction property of BMP-2, we hypothesized that EGCG could accelerate the bone healing process with an increased expression of BMP-2. In this manuscript, we studied whether the local use of EGCG can facilitate tibial fracture healing. Fifty-six 4-month-old rats were randomly assigned to two groups after being weight-matched: a control group with vehicle treatment (Ctrl) and a study group with 10 µmol/L, 40 µL, EGCG treatment (EGCG). Two days after the operation, the rats were treated daily with EGCG or vehicle by percutaneous local injection for 2 weeks. The application of EGCG enhanced callus formation by increasing the bone volume and subsequently improved the mechanical properties of the tibial bone, including the maximal load, break load, stiffness, and Young’s modulus. The results of the histology and BMP-2 immunohistochemistry staining showed that EGCG treatment accelerated the bone matrix formation and produced a stronger expression of BMP-2. Taken together, this study for the first time demonstrated that local treatment of EGCG can accelerate the fracture healing process at least partly via BMP-2.

[Display omitted] • Local EGCG injection suppressed the nociceptive TG neuronal activity. • Neuronal firing was dose-dependently inhibited by EGCG. • The inhibitory effect of EGCG lasted for 15 min and was reversible. • The potency of inhibition by EGCG almost equaled that of 1% lidocaine. • EGCG may be an effective treatment option for trigeminal pain. The phytochemical, polyphenolic compound, (-)-epigallocatechin-3-gallate (EGCG), is the main catechin found in green tea. Although a modulatory effect of EGCG on voltage-gated sodium and potassium channels has been reported in excitable tissues, the in vivo effect of EGCG on the excitability of nociceptive sensory neurons remains to be determined. Our aim was to investigate whether local administration of EGCG to rats attenuates the excitability of nociceptive spinal trigeminal nucleus caudalis (SpVc) neurons in response to mechanical stimulation in vivo. Extracellular single unit recordings were made from SpVc neurons in response to orofacial mechanical stimulation of anesthetized rats. The mean firing frequency of SpVc wide-dynamic range neurons following both non-noxious and noxious mechanical stimuli was significantly inhibited by EGCG in a dose-dependent and reversible manner. The mean magnitude of inhibition by EGCG on SpVc neuronal discharge frequency was similar to that of the local anesthetic, 1% lidocaine. Local injection of half-dose of lidocaine replaced the half-dose of EGCG. These results suggest that local injection of EGCG suppresses the excitability of nociceptive SpVc neurons, possibly via the inhibition of voltage-gated sodium channels and opening of voltage-gated potassium channels in the trigeminal ganglion. Therefore, administration of EGCG as a local anesthetic may provide relief from trigeminal nociceptive pain without side effects. [ABSTRACT FROM AUTHOR]

Chronic inflammatory diseases affect millions of people globally and the incidence rate is on the rise. While inflammation contributes to the tissue healing process, chronic inflammation can lead to life-long debilitation and loss of tissue function and organ failure. Chronic inflammatory diseases include hepatic, gastrointestinal and neurodegenerative complications which can lead to malignancy. Despite the millennial advancements in diagnostic and therapeutic modalities, there remains no effective cure for patients who suffer from inflammatory diseases. Therefore, patients seek alternatives and complementary agents as adjunct therapies to relieve symptoms and possibly to prevent consequences of inflammation. It iswell known that green tea polyphenols (GrTPs) are potent antioxidants with important roles in regulating vital signaling pathways. These comprise transcription nuclear factor-kappa B mediated I kappa B kinase complex pathways, programmed cell death pathways like caspases and B-cell lymphoma-2 and intervention with the surge of inflammatory markers like cytokines and production ofcyclooxygenase-2. This paper concisely reviews relevant investigations regarding protective effects of GrTPs and some reported adverse effects, as well as possible applications for GrTPs in the treatment of chronic and inflammatory complications. [ABSTRACT FROM AUTHOR]

Chronic arsenic exposure in drinking water is associated with the abnormalities of cardiac tissue. Excessive generation of ROS induced by arsenic has a central role in arsenic-induced cardiotoxicity. (-)-Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, possesses a potent antioxidant capacity and exhibits extensive pharmacological activities. This study was aim to evaluate the effect of EGCG on arsenic-induced cardiotoxicity in vivo and in vitro. Treatment with NaAsO 2 seriously affected the morphology and ultrastructure of myocardium, and induced cardiac injuries, oxidative stress, intracellular calcium accumulation and apoptosis in rats. In consistent with in vivo study, the injuries, oxidative stress and apoptosis were also observed in NaAsO 2 -treated H9c2 cells. All of these effects induced by NaAsO 2 were attenuated by EGCG. These results suggest EGCG could attenuate NaAsO 2 -induced cardiotoxicity, and the mechanism may involve its potent antioxidant capacity. [ABSTRACT FROM AUTHOR]

AIM (–)-Epigallocatechin-3-gallate (EGCG), a major compound of tea polyphenols, exhibited antitumor activity in previous studies. In these studies, EGCG usually inhibits EGFR, and impairs the ERK1/2 phosphorylation in tumor cells. The aim was to clarify the mechanism of ERK1/2 activation induced by EGCG. METHOD Jurkat and 293T cells were treated with EGCG in different culture conditions. Western Blotting (WB) was employed to analyze ERK1/2 and MEK phosphorylation. Cetuximab and FR180204 were used to inhibit cell signaling. The stability of EGCG was assessed by HPLC. The concentration of hydrogen peroxide generated by the auto-oxidation of EGCG was determined by photocolorimetric analysis. RESULTS Activation of ERK1/2 was observed to be both time-and dose-dependent. Stimulation of cell signaling was dependent on MEK activity, but independent of EGFR activity. Unexpectedly, EGCG was depleted within one hour of incubation under traditional culture conditions. Auto-oxidation of EGCG generated a high level of hydrogen peroxide in the medium. Addition of catalase and SOD to the acidic medium inhibited the oxidation of EGCG. However, this particular condition also prevented the phosphorylation of ERK1/2. The generation of ROS by hydrogen peroxide may also induce ERK1/2 activation in Jurkat cells. CONCLUSION ERK1/2 phosphorylation was caused by auto-oxidation of EGCG. Traditional culture conditions were determined to be inappropriate for EGCG research. [ABSTRACT FROM AUTHOR]

Abnormal angiogenesis in liver cirrhosis often leads to severe complications such as variceal haemorrhage and encephalopathy. Furthermore, splanchnic angiogenesis elevates portal pressure, in which angiogenic factors play pivotal roles. GTP (green tea polyphenol) extracted from Camellia sinensis has anti-angiogenic properties, but the effects on the parameters described above in cirrhosis have not been investigated. The aim of the present study was to determine the effects of GTP in cirrhosis and to investigate the underlying mechanism. Liver cirrhosis was induced in Spraque-Dawley rats by common BDL (bile duct ligation). They randomly received GTP or DW (distilled water, vehicle) for 28 days, then haemodynamic parameters, portosystemic shunting, mesenteric window vascular density, intrahepatic angiogenesis, liver fibrosis, plasma VEGF (vascular endothelial growth factor) concentration, mesenteric angiogenic factor and receptor protein expression, and serum and mesenteric oxidative stress parameters were assessed. Compared with the DW group, GTP significantly decreased portosystemic shunting, liver fibrosis, intrahepatic angiogenesis, mesenteric window vascular density, VEGF concentration and down-regulated the mesenteric HIF (hypoxia-inducible factor)-ޙ, VEGF and phospho-Akt expression. In conclusion, GTP ameliorates the severity of portosystemic shunting and mesenteric angiogenesis via the suppression of HIF-1α, Akt activation and VEGF. GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Polyphenols are the most abundant antioxidants in the human diet and are widespread constituents of fruits and beverages, such as tea, coffee, and wine. Epidemiological, clinical, and animal studies support a role of polyphenols in the prevention of various chronic diseases. For a long time, their direct antioxidant effect has been reported as the mechanism responsible for the observed health properties. However, recent findings revealed that polyphenols could interact with cellular signaling cascades regulating the activity of transcription factors and consequently affecting the expression of genes. Together with this classical regulatory pathway, polyphenols have been shown to affect the expression of microRNAs (miRNA). miRNAs are small, noncoding RNAs implicated in the regulation of gene expression that control both physiological and pathological processes such as development and cancer. Furthermore, expression of miRNAs can be affected by different external stimuli including nutrients such as vitamins, lipids, and phytochemicals. In this paper, we review studies assessing modulation of miRNAs expression by dietary polyphenols that could constitute a new pathway by which these compounds may exert their health effects. Over 100 miRNAs, involved in the control of different cellular processes such as inflammation or apoptosis, were identified as modulated by polyphenols. Most of the studies were performed in vitro using different cell lines, particularly cancer cell lines, and few studies were performed in animals. From all these data, miRNAs appear as interesting mediators in regulating polyphenols' biological effects; however, further studies are needed to validate miRNA targets and particularly in physiologically relevant conditions taking into account the bioavailability of dietary polyphenols. [Copyright &y& Elsevier]

Abstract: (-)-Epigallocatechin-3-gallate (EGCG), which has been attributed with numerous health benefits, is an oxidation sensitive, water soluble polyphenol. We have recently shown that heat-denatured β-Lactoglobulin (β-Lg) forms nanoparticles (<50 nm) with EGCG, which confer considerable protection to EGCG against oxidative degradation, useful for clear beverage enrichment. The current study aimed at advancing our understanding by further characterizing the structure, properties and performance of this new nanodelivery system to facilitate its application. We found that although particle size increased with rising EGCG concentration, zeta potential (based on the Smoluchowski model) stayed around −40 mV up to 8:1 M EGCG:β-Lg ratio, suggesting particles are very stable in solution. Good loading efficiency (60–70%) of EGCG within β-Lg nanocomplexes was obtained. The loading efficiency was mostly dependent on β-Lg concentration. Freeze-dried nanoparticles showed an IR absorbance spectrum different from the spectra summation of the pure components, confirming the molecular level complexation. Following freeze drying, the reconstituted complexes were very similar in size to the pre-frozen ones. The nanoentrapment dramatically suppressed the bitterness and astringency of EGCG. Simulated gastric digestion of β-Lg–EGCG nanoparticles showed limited release of EGCG, suggesting they could potentially be used as vehicles for protection of EGCG in the stomach, and for its sustained release in the intestine. Our results suggest that denatured β-Lg may serve as an effective natural vehicle for nanoencapsulation, protection and sustained release of EGCG and possibly other polyphenols for clear beverage enrichment. [Copyright &y& Elsevier]

This article is written to commemorate the contributions of Professor Tak-Hang (Bill) Chan to the field of chemistry and his collaborative efforts that have lead to insights pertaining to cancer cell biology and the development of potential cancer therapeutic agents. This article reviews the chronological scientific findings that evolved from a partnership between Bill Chan and Q. Ping Dou, spanning more than 10 years. While many compounds have been chemically synthesized by the Chan group and biologically scrutinized by the Dou group, the outcomes presented here will focus on green tea polyphenols as tumor proteasome inhibitors and anticancer agents. Furthermore, the biochemical alterations that increase or decrease the therapeutic potential of the polyphenol compounds in human cancer cells will also be discussed. [ABSTRACT FROM AUTHOR]

Although heme iron is an important form of dietary iron, its intestinal absorption mechanism remains elusive. Our previous study revealed that (-)-epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) markedly inhibited intestinal heme iron absorption by reducing the basolateral iron export in Caco-2 cells. The aim of this study was to examine whether small amounts of EGCG, GSE, and green tea extract (GT) could inhibit heme iron absorption, and to test whether the inhibitory action of polyphenols could be offset by ascorbic acid. A heme-Fe absorption study was conducted by adding various concentrations of EGCG, GSE, and GT to Caco-2 cells in the absence and presence of ascorbic acid. Polyphenolic compounds significantly inhibited heme-Fe absorption in a dose-dependent manner. The addition of ascorbic acid did not modulate the inhibitory effect of dietary polyphenols on heme iron absorption when the cells were treated with polyphenols at a concentration of 46 mg/L. However, ascorbic acid was able to offset or reverse the inhibitory effects of polyphenolic compounds when lower concentrations of polyphenols were added (≤ 4.6 mg/L). Ascorbic acid modulated the heme iron absorption without changing the apical heme uptake, the expression of the proteins involved in heme metabolism and basolateral iron transport, and heme oxygenase activity, indicating that ascorbic acid may enhance heme iron absorption by modulating the intracellular distribution of Fe. These results imply that the regular consumption of dietary ascorbic acid can easily counteract the inhibitory effects of low concentrations of dietary polyphenols on heme iron absorption but cannot counteract the inhibitory actions of high concentrations of polyphenols. Bioactive dietary polyphenols inhibit heme iron absorption in a dose-dependent manner. The small amounts of polyphenolic compounds present in foods are capable of reducing heme iron transport across the intestinal enterocyte. However, the inhibitory effects of dietary polyphenolic compounds on heme iron absorption can be offset by ascorbic acid and can possibly be avoided by decreasing the consumption of polyphenols while simultaneously taking ascorbic acid. [ABSTRACT FROM AUTHOR]

The activation of the EGFR (epidermal growth factor receptor) signalling pathway is one of the key mechanisms underlying the development of resistance to tamoxifen in breast cancer patients. As EGCG [(-)-epigallocatechin- 3-gallate], the most active catechin present in green tea, has been shown to down-regulate EGFR, we studied the effects of 10-100 μg/ml EGCG treatment on growth and invasion in a breast carcinoma cell line resistant to tamoxifen [MCF-7Tam (MCF-7 breast carcinoma cell line resistant to tamoxifen) cells] and parental MCF-7. A dosedependent down-regulation of EGFR mRNA expression and protein level occurred after 50 μg/ml EGCG treatment of MCF-7Tam cells. EGFR molecules on the plasma membrane surface of MCF-7Tam cells significantly decreased. EGFR phosphorylation (Tyr-992, Tyr-1045 and Tyr-1068) was higher in MCF-7Tam than in MCF-7 and it was reduced by EGCG treatment. ERK (extracellular regulated kinase) and phospho-ERK p42/44 were also down-regulated by EGCG treatment and in vitro cell growth and invasion decreased. MMP-2 (matrix metalloproteinase-2) and MMP-9, which are implicated in cell invasion and metastasis, and EMMPRIN (extracellular matrix metalloproteinase inducer), a glycoprotein able to activate MMPs, were significantly reduced after 50 μg/ml EGCG treatment. In keeping with this, TIMP-1 (tissue inhibitor of metalloproteinases-1) and TIMP-2, which down-regulate MMPs, increased after EGCG treatment. Altogether, the present data demonstrated that EGCG could attenuate the tamoxifen-resistant phenotype of MCF-7Tam cells. EGCG could stop MCF-7Tam cell growth and in vitro invasion through down-regulation of EGFR and other molecules implicated in aggressive biological behaviour. The present data support the hypothesis that EGCG is an interesting molecule to be investigated in tamoxifen-resistant breast carcinoma. [ABSTRACT FROM AUTHOR]

As a natural product, (-)-Epigallocatechin-3-gallate (EGCG), has demonstrated remarkable neuronal protection by depressing oxidative stress in Parkinson's disease (PD). However, the molecular mechanisms underlying EGCG neuronal protection have not been clarified. Using 6-hydroxydopamine (6-OHDA)-treated human neuroblastoma SH-SY5Y cells as a PD cell model, we found that 6-OHDA can cause neuronal death by regulating the activity of STAT3. Pretreatment of SH-SY5Y cells with EGCG (0.1–10 μM) significantly attenuated the cell death induced by 6-OHDA. In addition, the STAT3 activity decline induced by 6-OHDA in SH-SY5Y cells can be completely prevented by the presence of 1 μM of EGCG, and neuronal cell proliferation can be stimulated by EGCG treatment. These results clearly demonstrate that the disruption of STAT3 signaling by 6-OHDA makes significant contribution to the neuronal death in PD, and the protection of EGCG on neurons against oxidative stress-induced cell death may result from the re-stimulation of STAT3 signaling pathway. Our study not only clarified the role of STAT3 signaling pathway in oxidative stress-induced neuronal cell death, but also identified its involvement in the protection mechanism of EGCG on neurons in PD. The data resulting from our study also suggest that STAT3 may serve as a potential therapeutic target for the drug development in PD. [ABSTRACT FROM AUTHOR]

The article presents a study regarding epigallocathechin-3-gallate (EGCG). The study aims to evaluate the cytotoxicity using benzyl isothiocyanate (BITC) and hydrogen peroxide. Researchers state that cytotoxicity is inhibited by extracellular signal-regulated protein kinase (ERK) and c-jun N-terminal kinase (JNK).

To elucidate possible biochemical links between growth arrest from antiproliferative chemotherapeutic agents and apoptosis, our work has focused on agents (EGCg, capsaicin, cis platinum, adriamycin, anti-tumor sulfonylureas, phenoxodiol) that target tNOX. tNOX is a cancer-specific cell surface NADH oxidase (ECTO-NOX protein), that functions in cancer cells as the terminal oxidase for plasma membrane electron transport. When tNOX is active, coenzyme Q_{10} (ubiquinone) of the plasma membrane is oxidized and NADH is oxidized at the cytosolic surface of the plasma membrane. However, when tNOX is inhibited and plasma membrane electron transport is diminished, both reduced coenzyme Q_{10} (ubiquinol) and NADH would be expected to accumulate. To relate inhibition of plasma membrane redox to increased ceramide levels and arrest of cell proliferation in G_{1} and apoptosis, we show that neutral sphingomyelinase, a major contributor to plasma membrane ceramide, is inhibited by reduced glutathione and ubiquinone. Ubiquinol is without effect or stimulates. In contrast, sphingosine kinase, which generates anti-apoptotic sphingosine-1-phosphate, is stimulated by ubiquinone but inhibited by ubiquinol and NADH. Thus, the quinone and pyridine nucleotide products of plasma membrane redox, ubiquinone and ubiquinol, as well as NAD^{+} and NADH, may directly modulate in a reciprocal manner two key plasma membrane enzymes, sphingomyelinase and sphingosine kinase, potentially leading to G_{1} arrest (increase in ceramide) and apoptosis (loss of sphingosine-1-phosphate). As such, the findings provide potential links between coenzyme Q_{10}-mediated plasma membrane electron transport and the anticancer action of several clinically-relevant anticancer agents. [ABSTRACT FROM AUTHOR]

Tea polyphenols, including (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin-3-gallate (EGCG), have been shown to possess potent antioxidant and anticancer activities. The aim of this study was to evaluate the possibility of using liposomes for the local delivery, including skin and tumor deposition, of these polyphenols. Liposomes containing egg phosphatidylcholine, cholesterol, or anionic species were prepared by a solvent evaporation method and then were subjected to a probe sonicator. The size, zeta potential and entrapment efficiency of these liposomal formulations were determined to provide correlations with results from a subsequent in vivo study. The release rate study showed that inclusion of an anionic species, such as deoxycholic acid (DA) or dicetyl phosphate (DP), increased the permeability of the lipid bilayers, leading to the rapid release of these formulations. No significant increase in skin deposition of catechins was observed after topical application of liposomes. On the other hand, a greater amount of catechins were delivered into the solid tumor by liposomes than by the aqueous solution. The drug release rate and vesicle size of liposomes may influence drug deposition in tumor tissues. The isomers, (+)-catechin and (-)-epicatechin, showed different physicochemical properties in liposomes and for local deposition in the skin and tumor. Finally, the presence of gallic acid ester in the structure of EGCG significantly increased the tissue uptake of catechins. [ABSTRACT FROM AUTHOR]

Purpose: A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG), has been known to possess anti-cancer properties. In this study, we investigated the time-course anticancer effects of EGCG on human ovarian cancer cells to provide insights into the molecular-level understanding of growth suppression mechanism involved in EGCG-mediated apoptosis and cell cycle arrest.Methods: Three human ovarian cancer cell lines (p53 negative, SKOV-3 cells; mutant type p53, OVCAR-3 cells; and wild type p53, PA-1 cells) were used. The effect of EGCG treatment was studied via cell count assay, cell cycle analysis, FACS, Western blot, and macroarray assay.Results: EGCG exerts a significant role in suppressing ovarian cancer cell growth. Also, EGCG showed growth inhibitory effects in each cell line in a dose-dependent fashion and induced apoptosis and cell cycle arrest. The cell cycle was arrested at the G1 phase by EGCG in SKOV-3 and OVCAR-3 cells. In contrast, the cell cycle was arrested in the G1/S phase arrest in PA-1 cells. EGCG differentially regulated the expression of genes and proteins (Bax, p21, Retinoblastoma, cyclin D1, CDK4, Bcl-XL) more than 2-fold, showing a possible gene regulatory role of EGCG. The continual expression in p21WAF1 suggests that EGCG acts in the same way with p53 proteins to facilitate apoptosis after EGCG treatment. And Bax, PCNA, and Bcl-X are important in EGCG-mediated apoptosis. In contrast, CDK4 and Rb are not important in ovarian cancer cell growth inhibition.Conclusion: EGCG can inhibit ovarian cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of cell cycle-related proteins. Thereby, the EGCG-mediated apoptosis can be applied to an advanced strategy in the development of a potential drug against ovarian cancer. [Copyright &y& Elsevier]

Capsaicin and the principal green tea catechin, (-)-epigallocatechin-3-gallate (EGCg), target tNOX, a tumor (cancer)-specific surface hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity (ECTO-NOX protein). Accordingly vector-forced over expression of tNOX in MCF-10A mammary epithelia or COS cells that lack tNOX or in COS cells that underexpress tNOX enhanced the susceptibility of growth and apoptosis to both EGCg and capsaicin. Additionally, the tNOX-transfected MCF-10A cells proliferated in Matrigel, a measure of invasiveness. In contrast, oligomeric antisense tNOX DNA abrogated growth inhibition by EGCg and capsaicin and reduced anchorage-dependent growth of HeLa (human cervical carcinoma) cells that naturally overexpress tNOX. The findings show cell surface expression of tNOX as both necessary and sufficient for the cellular anticancer activities attributed to both EGCg and capsaicin. [ABSTRACT FROM AUTHOR]

The article discusses a research done on the end products of green tea (—)-Epigallocatechin-3-gallate (EGCG) on the mRNA level and the uncoupling protein 2 (UCP2) promoter activity. It notes that the UCP2 stimulates heat production by the uncoupling respiration from adenosine triphosphate (ATP). It notes that through EGCG treatment, the regulated mRNA level of UCP2 has increased. The result shows that green tea EGCG directly regulates UCP2 gene expression.

• Antioxidant high internal phase emulsion (HIPE) gels as nutraceutical containers were reported. • Co-assembled soy β -conglycinin-EGCG nanoparticles as HIPE stabilizers were fabricated. • The HIPE gels exhibited excellent thermal and storage stability. • The HIPE gels displayed an excellent oxidative protection of encapsulated lipophilic nutraceuticals. • The oxidative protection of the HIPEs was modulated by the EGCG loading amount in the nanoparticles. This work reports a kind of novel antioxidant Pickering high internal phase emulsions (HIPEs; with an oil fraction, ϕ > 0.74) stabilized by soy β -conglycinin (β -CG) and polyphenol complex nanoparticles, as outstanding protective containers for lipophilic nutraceuticals. The nanoparticles with a representative polyphenol ((-)-epigallocatechin-3-gallate; EGCG) encapsulated were fabricated through an ethanol-mediated dissociation and re-assembly process of β -CG, with greater particle size and higher surface hydrophilicity observed at higher initial EGCG concentrations. Using these co-assembled nanoparticles as sole stabilizers, a kind of HIPE gels with similar gel stiffness and microstructure, could be easily fabricated at ϕ = 0.8 and a protein concentration in the aqueous phase of 1.0 wt% using polyunsatuated fatty acid-rich flaxseed oil as the dispersed phase. These HIPE gels were extraordinarily stable against heating or long-term storage, but susceptible to freeze-thawing. The as-fabricated HIPEs showed an excellent protection to β -carotene (encapsulated in oil phase) against heating, as well as an inhibition of lipid oxidation. The oxidation protection was in an EGCG concentration dependent manner. The results would be of interest for providing a novel strategy to fabricate functionalized Pickering HIPEs as potential containers or delivery systems for lipophilic nutraceuticals. [ABSTRACT FROM AUTHOR]

Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance the osteogenic differentiation of murine bone marrow mesenchymal stem cells and inhibit the osteoclastogenesis in RAW264.7 cells by modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) (RANK/RANKL/OPG) pathway. Our previous study also found that EGCG can promote bone defect healing in the distal femur partially via bone morphogenetic protein-2 (BMP-2). Considering the osteoinduction property of BMP-2, we hypothesized that EGCG could accelerate the bone healing process with an increased expression of BMP-2. In this manuscript, we studied whether the local use of EGCG can facilitate tibial fracture healing. Fifty-six 4-month-old rats were randomly assigned to two groups after being weight-matched: a control group with vehicle treatment (Ctrl) and a study group with 10 µmol/L, 40 µL, EGCG treatment (EGCG). Two days after the operation, the rats were treated daily with EGCG or vehicle by percutaneous local injection for 2 weeks. The application of EGCG enhanced callus formation by increasing the bone volume and subsequently improved the mechanical properties of the tibial bone, including the maximal load, break load, stiffness, and Young's modulus. The results of the histology and BMP-2 immunohistochemistry staining showed that EGCG treatment accelerated the bone matrix formation and produced a stronger expression of BMP-2. Taken together, this study for the first time demonstrated that local treatment of EGCG can accelerate the fracture healing process at least partly via BMP-2. [ABSTRACT FROM AUTHOR]

Background: (-)-Epigallocatechin-3-gallate (EGCG), a major component of green tea, has been found to inhibit the influenza virus. However, the mechanism of EGCG anti-influenza virus effect needs to be further explored., Methods: BEAS-2B cells were treated with different concentrations of EGCG or were treated with EGCG for different times. CCK8 assay was used to detect the cell viability, and quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay were employed to measure the interferon (IFN)-λ2 mRNA and protein expression levels. The phospho-p38 mitogen-activated protein kinase (P-p38 MAPK), phospho-extracellular signal-regulated kinase (P-ERK), and phospho-c-Jun N-terminal kinase (P-JNK) expression were tested by western blot. Then, p38 MAPK, ERK, and JNK inhibitor were used to study the effect of p38 MAPK, ERK, and JNK signaling pathways on IFN-λ2 expression. The BEAS-2B cells were treated with EGCG, EGCG and IFN λ2 neutralizing antibody or control antibody for 12 h, and were infected with influenza A virus (IAV) (H1N1) for 1 h. After 12 h, nucleoprotein (NP) mRNA and protein expression levels of H1N1 were assessed by qRT-PCR and western blot., Results: The IFN-λ2 mRNA and protein expression levels in BEAS-2B cells were up-regulated after EGCG (treatment in time- and dose-dependent manners the concentration range from 0 to 50 µg/mL had no cytotoxicity). Meanwhile, the P-p38 MAPK, P-ERK, and P-JNK expression levels were up-regulated. IFN-λ2 mRNA and protein expression was inhibited after p38 MAPK inhibitor pre-treatment, but not by ERK and JNK inhibitors. Furthermore, the expression of H1N1 NP gene and protein decreased after EGCG pre-treatment, while IFN-λ2 neutralizing antibody attenuated the effect of EGCG inhibiting the expression of H1N1 NP gene and protein., Conclusions: EGCG inhibited IAV H1N1 by inducing the expression of IFN-λ2 in BEAS-2B cells through the p38 MAPK signaling pathway., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

The survival of motor neurons (MNs) is the key to recovery of the motor function after brachial plexus root avulsion (BPRA). (-)-epigallocatechin-3-gallate (EGCG) exerts neuroprotective roles in neurons under different pathological conditions. However, the role of EGCG in regulating motor neurons under BPRA remains to be unclear. In the present study, we investigated the functional role of EGCG both in vitro and in vivo . In an in vitro study, we observed that EGCG obviously increased the cell survival rate of MNs and FIG4 protein levels compared with the vehicle control, with a peak level observed at 50 µM; EGCG can also upregulate FIG4 to reduce the cell death of MNs and increase the neurite outgrowth under oxidative stress; moreover, EGCG can upregulate FIG4 to promote the functional recovery and the survival of MNs in the ventral horn in mice after BPRA. These combined results may lay the foundation for EGCG to be a novel strategy for the treatment of BPRA.

Portal hypertension is the main complication of cirrhosis and represents a leading cause of death in patients with chronic liver disease. Therapeutic agents to improve portal hypertension should ameliorate the underlying mechanisms of portal hypertension: the elevated hepatic resistance and the hyperdynamic circulation. In the present issue of Clinical Science, Hsu and co-workers show the beneficial effects of GTPs (green tea polyphenols) in improving portal hypertension. Long-term administration of GTPs inhibited the development of cirrhosis and portal hypertension by decreasing both hepatic resistance and splanchnic hyperdynamic circulation. The main underlying mechanism of the benefits of GTPs appears related to the down-regulation of splanchnic angiogenesis. The present study adds further evidence supporting the potential of natural compounds for an effective nutriceutical approach to the treatment of patients with cirrhosis of the liver. [ABSTRACT FROM AUTHOR]

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., Competing Interests: CONFLICTS OF INTEREST The authors state no conflicts of interest.

Epidermal growth factor receptor (EGFR) expression is an important marker in breast carcinoma pathology and is considered a pivotal molecule for cancer cell proliferation, invasion and metastasis. We investigated the effects of epigallocatechin-3-gallate (EGCG), the most active green tea catechin, in combination with 6-OH-11-O-hydroxyphenanthrene (IIF), a synthetic retinoid X receptor-γ (RXRγ) agonist, on three breast carcinoma cell lines: MCF-7, MCF-7TAM and MDA-MB-231. EGFR and AKT activation and molecular markers of cell motility and migration (CD44, extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN), MMP-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMPs)) were studied after EGCG and IIF treatments. The EGCG + IIF treatment was the most active in down-regulating EGFR phosphorylation at Tyr 1068 in all the investigated cell lines; p473AKT was also down-regulated in MCF-TAM cells. EGCG + IIF was also the most active treatment in reducing the expression of markers of invasion and migration in all the three cell lines: CD44, EMMPRIN, MMP-2 and -9 expression decreased, whereas TIMPs were up-regulated. Zymography and scratch assay also confirmed the reduced invasion tendency. We considered that EGCG and IIF treatments could alter the molecular network based on EGFR, CD44 and EMMPRIN expression interdependence and reduced the migration tendency in MCF-7, MCF-7TAM and MDA-MB-231 cells. These events only occurred in association with AKT inactivation in MCF-7TAM cells. In conclusion, the combination of EGCG and IIF significantly attenuated the invasive behaviour of breast carcinoma cells., (© 2017 The Author(s).)

Background/aims: Exposure to arsenic in individuals has been found to be associated with various health-related problems including skin lesions, cancer, and cardiovascular and immunological disorders. (-)-Epigallocatechin-3-gallate (EGCG), the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, anti-apoptotic and anti-inflammatory activity in vivo and in vitro. Thus, the present study was conducted to investigate the protective effects of EGCG against arsenic-induced inflammation and immunotoxicity in mice., Methods: Serum IL-1β, IL-6 and TNF-α were determined by ELISA, tissue catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), nitric oxide and caspase 3 by commercial kits, mitochondrial membrane potential with Rh 123, mitochondrial ROS with 2',7'-dichlorofluorescin diacetate (DCFH-DA), apoptotic and necrotic cells and T-cell phenotyping with Flow cytometry analysis., Results: The results showed that arsenic treatment significantly increased oxidative stress levels (as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione and reactive oxygen species), increased levels of inflammatory cytokines and promoted apoptosis. Arsenic exposure increased the relative frequency of the CD8+(Tc) cell subpopulation (from 2.8 to 18.9%) and decreased the frequency of CD4+(Th) cells (from 5.2 to 2.7%). Arsenic exposure also significantly decreased the frequency of T(CD3) (from 32.5% to 19.2%) and B(CD19) cells (from 55.1 to 32.5%). All of these effects induced by NaAsO2 were attenuated by EGCG., Conclusions: The present in vitro findings indicate that EGCG attenuates not only NaAsO2-induced immunosuppression but also inflammation and apoptosis., (© 2017 The Author(s)Published by S. Karger AG, Basel.)

In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins from green tea leaves, on activities of cyclooxygenase (COX)-1 and thromboxane synthase (TXAS), thromboxane A2 (TXA2) production associated microsomal enzymes. EGCG inhibited COX-1 activity to 96.9%, and TXAS activity to 20% in platelet microsomal fraction having cytochrome c reductase (an endoplasmic reticulum marker enzyme) activity and expressing COX-1 (70 kDa) and TXAS (58 kDa) proteins. The inhibitory ratio of COX-1 to TXAS by EGCG was 4.8. These results mean that EGCG has a stronger selectivity in COX-1 inhibition than TXAS inhibition. In special, a nonsteroid anti-inflammatory drug aspirin, a COX-1 inhibitor, inhibited COX-1 activity by 11.3% at the same concentration (50 μM) as EGCG that inhibited COX-1 activity to 96.9% as compared with that of control. This suggests that EGCG has a stronger effect than that of aspirin on inhibition of COX-1 activity. Accordingly, we demonstrate that EGCG might be used as a crucial tool for a strong negative regulator of COX-1/TXA2 signaling pathway to inhibit thrombotic disease-associated platelet aggregation.

In the current era of antiretroviral treatment, the prevalence of HIV-associated dementia is on the rise. Many past works have associated inflammation and neuronal loss with cognitive deficits inherent to the syndrome. Importantly, HIV-1 induced astrogliosis has been shown to play a central role in this process. Here we examined the effect of green tea derived (-)-epigallocatechin-3-gallate (EGCG) food supplementation for its ability to modulate GFAP expression and neuronal loss in an HIV-1 Tat transgenic mouse model whose expression was controlled by a brain specific doxycycline promoter. By immunohistochemistry we found that EGCG (300mg/kg/day) dramatically reduced astrogliosis as demonstrated by GFAP expression. This was accompanied by a mild reduction in activated microglia by Iba-1 staining and significant reduction in neuronal loss through apoptosis as demonstrated by MAP2 staining and Western blot analysis respectively. Future studies will be required to determine intracellular mechanism involved in EGCG mediated downregulation of GFAP and associated astrocytosis and neuronal loss.