Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity.

Epidemiological studies have shown that the consumption of green tea has beneficial effects against cancer. Basic studies have provided evidence that epigallocatechin gallate (EGCG) is a major contributor to these effects. Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases with the ability to degrade the extracellular matrix proteins and are involved in various diseases including cancer in which MMPs have a critical role in invasion and metastasis. In this review, we discuss the effects of EGCG on several types of MMPs in the context of its anticancer activity. In the promoter region, MMPs have binding sites for at least one transcription factor of AP-1, Sp1, and NF-κB, and EGCG can downregulate these transcription factors through signaling pathways mediated by reactive oxygen species. EGCG can also decrease nuclear ERK, p38, heat shock protein-27 (Hsp27), and ß-catenin levels, leading to suppression of MMPs' expression. Other mechanisms by which EGCG inhibits MMPs include direct binding to MMPs to prevent their activation and downregulation of NF-κB to suppress the production of inflammatory cytokines such as TNFα and IL-1ß. Findings from studies on EGCG presented here may be useful in the development of more effective anti-MMP agents, which would give beneficial effects on cancer and other diseases.

Virulent Pseudomonas aeruginosa pneumonia in an immunocompetent adult associated with a home whirlpool bath: A case report.

We present a case of life-threatening pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) in a healthy 67-year-old man. Rapid disseminated infection resulted in the right hemorrhagic pneumonia and bacteremia. Antimicrobial therapy had limited effects, radical pneumonectomy eventually resolved the prolonged infection. Concurrently, we explored the environmental factors responsible for fulminant P. aeruginosa infection. Multi-locus sequence typing demonstrated that P. aeruginosa isolated from the patient was identical to that collected from home whirlpool bath by the common virulent factor gene. Massive inhalation of contaminated aerosol and pathogen virulence may have synergistically contributed to the severity in this case.

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies.

Epidemiological and laboratory studies have shown that green tea and green tea catechins exert beneficial effects on a variety of diseases, including cancer, metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most cases, (-)-epigallocatechin gallate (EGCG) has been shown to play a central role in these effects by green tea. Catechins from other plant sources have also shown health benefits. Many studies have revealed that the binding of EGCG and other catechins to proteins is involved in its action mechanism. Computational docking analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed information on catechin-protein interactions. Several of these studies have revealed that the galloyl moiety anchors it to the cleft of proteins through interactions with its hydroxyl groups, explaining the higher activity of galloylated catechins such as EGCG and epicatechin gallate than non-galloylated catechins. In this paper, we review the results of CMDA and XCA of EGCG and other plant catechins to understand catechin-protein interactions with the expectation of developing new drugs with health-promoting properties.

Dietary supplementation with (-)-epigallocatechin-3-gallate reduces inflammatory response in adipose tissue of non-obese type 2 diabetic Goto-Kakizaki (GK) rats.

(-)-Epigallocatechin gallate (EGCG), a major catechin in green tea, is an antioxidant associated with the reduction of oxidative stress in vitro. However, the mechanisms underlying the effects of EGCG on adipose tissue-related metabolic disturbances in vivo are not understood. This study examined whether dietary supplementation of EGCG reduces the oxidative stress-associated inflammatory response in the mesenteric adipose tissue of non-obese type 2 diabetic Goto-Kakizaki (GK) rats. GK rats were fed a normal diet or diet containing 0.1, 0.2, or 0.5% EGCG (w/w) for 25 weeks. The mRNA levels of IL-1ß were significantly reduced in GK rats given 0.1% EGCG (0.059 ± 0.008; means ± SEM in arbitrary unit) compared with those in GK rats given a control diet (0.135 ± 0.011), but not in those given 0.2% EGCG (0.123 ± 0.012) or 0.5% EGCG (0.112 ± 0.019). The mRNA and protein level of other genes for inflammatory responses such as IL-18, TNF-α, MCP-1, CD11s, CD18, and resistin were also significantly reduced in rats given 0.1% EGCG, but not in those given ≥ 0.2% EGCG. This suggests that supplementation with EGCG at relatively low concentrations (0.1%) in GK rats reduces expression of genes and proteins involved in inflammation in adipose tissue.

Dietary supplementation with a low dose of (-)-epigallocatechin-3-gallate reduces pro-inflammatory responses in peripheral leukocytes of non-obese type 2 diabetic GK rats.

(-)-Epigallocatechin-3-gallate (EGCG), which is largely found in green tea, is known to eliminate reactive oxygen species and associated inflammatory responses in vitro and in cells. However, the in vivo mechanisms underlying the effects of EGCG on the amelioration of metabolic disorders are not fully understood. In this study, we examined whether dietary supplementation with EGCG reduces inflammatory responses in peripheral leukocytes of a non-obese type 2 diabetes animal model, Goto-Kakizaki (GK) rats. GK rats at 9 wk of age were fed a control high-fat diet (46 energy % from lard and corn oil) or a high-fat diet containing 0.1%, 0.2%, or 0.5% EGCG (w/w) for 25 wk. The oxidative stress markers 8-hydroxydeoxyguanosine (OHdG) and total malondialdehyde (MDA) were reduced by supplementation with EGCG at 0.1%, but not at 0.2% or more. Significant reductions in the mRNA levels of genes related to inflammatory responses (TNF-α, IFN-γ, IL-1ß, IL-6, IL-18, MCP-1, CD11b, and S100a6), 8-OHdG, and total MDA were induced in peripheral leukocytes of GK rats by EGCG supplementation at 0.1%, but not at 0.2% or more, compared with rats fed the control diet. The present results suggest that supplementation with a low dose of EGCG reduces oxidative stress and the expressions of genes involved in inflammation in peripheral leukocytes of GK rats.

Effects of a catechin-free fraction derived from green tea on gene expression of enzymes related to lipid metabolism in the mouse liver.

Many biological activities of green tea have been attributed to a major constituent, (minus;)-epigallocatechin gallate (EGCG). We previously reported that EGCG and an EGCG-free fraction derived from green tea modulated the gene expression of gluconeogenic enzymes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, in the mouse liver. EGCG is also known to affect the gene expression of enzymes related to lipid metabolism. However, it remains to be examined whether or not a constituent other than EGCG contributes to the change in gene expression of these enzymes. In this study, we prepared an EGCG-free water-soluble fraction (GT-W), and examined its effects on the hepatic gene expression of lipogenic enzymes in mice. The results of quantitative real-time PCR assays indicated that the dietary administration of GT-W for 4 weeks reduced the hepatic gene expression of lipogenic enzymes: fatty acid synthase, hydroxymethylglutaryl coenzyme A reductase, and acetyl-coenzyme A carboxylase alpha. Also, the gene expression of sterol regulatory element-binding transcription factor (Srebf)1 and/or Srebf2 was reduced, suggesting that the reduction of Srebfs contributed to the down-regulation of the lipogenic enzymes, since these transcription factors bind the promoter region to enhance their expression. The plasma levels of triglycerides and cholesterol were reduced with statistical significance in the group given a diet containing GT-W. These results suggest that in addition to EGCG, green tea contains some component(s) which may help to prevent arteriosclerosis and obesity.

Analysis of risk factors associated with complications of hyperbaric oxygen therapy.

PURPOSE: The aim of this study was to verify independent risk factors of pressure equalization problems associated with hyperbaric oxygen (HBO(2)) therapy. METHODS: We reviewed a single-institutional study of 1609 patients with 17604 treatments who had HBO(2) therapy in a multiplace chamber, in which the factors examined and their relationship to complications were assessed, using multivariate analyses, to determine the significantly independent risk factors of complications related to HBO(2) therapy. RESULTS: The compression rate was 0.067 atmospheres absolute/min (6.8 kPa/min). Pressure equalization problems of the middle ear, expressed as pain or discomfort, such as cranial sinus pain, and teeth pain were observed in 156 patients (9.7%). Sixty-six of them could not continue HBO(2) therapy because of these problems. Peripheral circulatory disorders with refractory ulcers or nonhealing wounds and the interval between clinical symptoms and the first day of HBO(2) therapy were independent risk factors of pressure equalization problems. Independent risk factors of cessation due to pressure equalization problems were identified as age more than 61 years, female sex, and interval between symptoms and the first day of HBO(2) therapy. CONCLUSION: It is suggested that chamber compression must be performed with particular care when patients have peripheral circulatory disorders and have short interval between clinical symptoms and the first day of HBO(2) therapy.

The anti-fibrotic effect of green tea with a high catechin content in the galactosamine-injured rat liver.

Previously, we reported that the oral administration of green tea rich in catechins restored levels of several biomarkers increasing in galactosamine-treated rats to nearly control values. These biomarkers included serum transaminase activities, serum concentrations of tumor necrosis factor-alpha and interleukin 1-beta, and the hepatic mRNA expression of these inflammatory cytokines. In the present study, we examined possible anti-fibrotic effects of green tea in galactosamine-induced hepatitis. The results of the reverse transcription and polymerase chain reaction indicated that the increase in gene expression of the alpha1 chain of collagen type 1 and transforming growth factor beta-1 in the injured liver 24 h post-injection of galactosamine was suppressed by the administration of green tea. Masson's trichrome staining demonstrated that the extent of fibrogenesis after 14 days was greater in the galactosamine-injured livers not treated with green tea than the treated ones. These results suggest that the drinking of green tea with a high catechin content may help to prevent and/or attenuate the development of fibrosis in hepatitis.

Green tea with a high catechin content suppresses inflammatory cytokine expression in the galactosamine-injured rat liver.

Galactosamine is known to induce hepatic injury in rats and the galactosamine-induced hepatitis is believed to be similar to viral hepatitis both morphologically and functionally. In the present study, we examined how drinking green tea affects the gene expression of inflammatory cytokines which may be up-regulated in galactosamine-induced hepatitis. As has been reported, galactosamine caused hepatic injury in rats as evidenced by an increase in serum transaminase activities and histological observations of the liver. The results of the reverse transcription and polymerase chain reaction indicated an increased gene expression of inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta, in the injured liver and the enzyme linked immunoassay showed an increase in the serum levels of these cytokines. Oral administration of green tea rich in catechins (Healthya green tea) restored these biomarkers in the galacotsamine-treated rats to near the control levels. These results suggest that the drinking of green tea with a high catechin content may help to prevent and/or attenuate the development of a certain type of hepatitis.

Effects of tea constituents on cell cycle progression of human leukemia U937 cells.

Tea and tea constituents are known to induce apoptosis in a variety of cancerous cells, suggesting their beneficial effects as chemopreventive agents. Previous studies have shown that low molecular weight constituent catechins and high molecular weight fractions of tea have the apoptosis-inducing activity, but that their action mechanisms may be different. Since cell cycle arrest is known to be one of the underlying mechanisms of apoptosis, we examined the effects of these tea constituents on cell cycle progression of human leukemia U937 cells. The results showed that the high molecular weight fractions of green tea and black tea caused G2/M arrest associated with up-regulation of p21/Waf1, but that epigallocatechin gallate, a major component of green tea catechins, gave little effects of cell cycle progression and p21/Waf1 expression. Thus, the present results suggest the difference in the apoptosis-induction mechanism between the two types of tea constituents.