Dose-dependent levels of epigallocatechin-3-gallate in human colon cancer cells and mouse plasma and tissues.
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Epigallocatechin-3-gallate (EGCG; molecular formula: C22H18011)is the most abundant catechin in green tea (Camellia sinensis Theaceae). Both EGCG and green tea have been shown to have cancer-preventive activity in a number of animal models, and numerous mechanisms have been proposed based on studies with human cell lines. EGCG has been shown to undergo extensive biotransformation to yield methylated and glucuronidated metabolites in mice, rats, and humans. In the present study, we determined the concentration-dependent uptake of EGCG by HT-29 human colon cancer cells (20-600 microM) and the dose dependence of EGCG plasma and tissue levels after a single dose of EGCG (50-2000 mg/kg i.g.) to male CF-1 mice. The cytosolic levels of EGCG were linear with respect to extracellular concentration of EGCG after treatment of HT-29 cells for 2 h (915.3-6851.6 microg/g). In vivo, EGCG exhibited a linear dose relationship in the plasma (0.03-4.17 microg/ml), prostate (0.01-0.91 microg/g), and liver (0.09-18.3 microg/g). In the small intestine and colon, however, the levels of EGCG plateaued between 500 and 2000 mg/kg i.g. These results suggest that absorption of EGCG from the small intestine is largely via passive diffusion; however, at high concentrations, the small intestinal and colonic tissues become saturated. The levels of 4''-O-methyl-EGCG and 4',4''-di-O-methyl-EGCG parallel those of EGCG with respect to dose. The present study provides information with respect to what concentrations of EGCG are achievable in mice and may guide dose selection for future cancer chemoprevention studies with EGCG. (+info)
The effect of an herbal supplement containing black tea and caffeine on metabolic parameters in humans.
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OBJECTIVE: The objective of this study was to test an herbal supplement containing black tea (the fully oxidized form of Camellia sinensis) and caffeine for stimulation of thermogenesis. METHODS/MATERIALS: A double-blind, placebo-controlled, crossover study was conducted on 16 healthy, weight-stable, non-smoking subjects, ages 21-55 years, with body mass index (BMI) of 20-30 kg/m2, and on no medications other than oral contraceptives or hormone replacement therapy. Subjects had no caffeine for 48 hours, no exercise for 24 hours, and no food for 12 hours before each visit. Area under the curve (AUC) for resting metabolic rate (RMR), respiratory quotient (RQ), blood pressure, pulse rate, and temperature were measured. At each visit RMR was measured at baseline and at one and two hours following oral administration of a supplement containing principally 600 mg black tea extract (60 percent polyphenols, 20 percent caffeine) and 442 mg guarana extract (36 percent caffeine) or matching placebo. RESULTS: The RMR and systolic blood pressure (SBP) AUCs increased significantly (p less than 0.02 and p less than 0.01, respectively) in the herbal supplement group compared to placebo. The AUC increase in RMR over the two-hour test period was 77.19 kcal/24 hr2 +/- 120.10 kcal/24 hr2 with an average rise of 52.38 +/- 29.52 kcal/24 hrs. The AUC rise in SBP over two hours was 10.3 mm Hg/hr +/- 14 mm Hg/hr. The average rise in SBP over two hours was 3.7 mm Hg +/- 4.4 mm Hg. DISCUSSION: The herbal supplement increased metabolic rate without changing substrate oxidation. The rise in SBP was consistent with the amount of caffeine the supplement contained. (+info)
Green tea extract and its major polyphenol (-)-epigallocatechin gallate improve muscle function in a mouse model for Duchenne muscular dystrophy.
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Duchenne muscular dystrophy is a frequent muscular disorder caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that contributes to the stabilization of muscle fiber membrane during muscle activity. Affected individuals show progressive muscle wasting that generally causes death by age 30. In this study, the dystrophic mdx(5Cv) mouse model was used to investigate the effects of green tea extract, its major component (-)-epigallocatechin gallate, and pentoxifylline on dystrophic muscle quality and function. Three-week-old mdx(5Cv) mice were fed for either 1 or 5 wk a control chow or a chow containing the test substances. Histological examination showed a delay in necrosis of the extensor digitorum longus muscle in treated mice. Mechanical properties of triceps surae muscles were recorded while the mice were under deep anesthesia. Phasic and tetanic tensions of treated mice were increased, reaching values close to those of normal mice. The phasic-to-tetanic tension ratio was corrected. Finally, muscles from treated mice exhibited 30-50% more residual force in a fatigue assay. These results demonstrate that diet supplementation of dystrophic mdx(5Cv) mice with green tea extract or (-)-epigallocatechin gallate protected muscle against the first massive wave of necrosis and stimulated muscle adaptation toward a stronger and more resistant phenotype. (+info)
Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B.
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Most known interactions between herbal extracts and drugs involve the inhibition of drug-metabolizing enzymes, but little is yet known about the possible role of transporters in these interactions. In this study, we have examined the effects of herbal extracts used in dietary supplements on the function of organic anion-transporting polypeptide B (OATP-B; OATP2B1), which is expressed on human intestinal epithelial cells and is considered to be involved in the intestinal absorption of various drugs. Specifically, the effects of 15 herbal extracts on uptake of estrone-3-sulfate, a typical OATP-B substrate, by human embryonic kidney 293 cells stably expressing OATP-B were evaluated. At concentration levels considered likely to be attainable in the human intestine, extracts of bilberry, echinacea, green tea, banaba, grape seed, ginkgo, and soybean potently inhibited estrone-3-sulfate uptake by 75.5, 55.5, 82.1, 61.1, 64.5, 85.4, and 66.8%, respectively (P < 0.01). The inhibitory effect of ginkgo leaf extract was concentration-dependent (IC(50) = 11.2 +/- 3.3 microg/ml) and reversible. Moreover, flavonol glycosides and catechins significantly inhibited the function of OATP-B, suggesting that the inhibitory effects of the herbal extracts on OATP-B may be primarily attributable to flavonoids. The extracts of mulberry, black cohosh, and Siberian ginseng moderately (but significantly) inhibited estrone-3-sulfate uptake by 39.1, 47.2, and 49.2%, respectively (P < 0.05). Extracts of barley, Job's tears, rutin, rafuma, and passionflower were ineffective. These results suggest that coadministration of some dietary supplements may decrease the absorption of orally administered substrates of OATP-B. (+info)
Synthesis of lyoniresinol with combined utilization of synthetic chemistry and biotechnological methods.
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We have synthesized lyoniresinol with the combined utilization of synthetic chemistry and biotechnological methods, specifically using plant cell cultures as an "enzyme source." (+info)
Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1.
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BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans. DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment. RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans. (+info)
Inhibition of IL-8 production by green tea polyphenols in human nasal fibroblasts and A549 epithelial cells.
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The attraction of leukocytes to tissues is essential in order for inflammation and the host response to infection to occur. Airway inflammation is a very common cause illness with a substantial impact on health care. Neutrophils play an essential role in the host defense and in inflammation, but the latter may trigger and sustain the pathogenesis of a range of acute and chronic diseases. Infiltration of neutrophils occurs as a response to chemoattractant molecules by resident tissue cells. The recruitment of neutrophils in airway inflammation may account for the generation of IL-8. To evaluate the effectiveness of green tea polyphenols in the modulation of airway inflammation through the blocking of neutrophil chemokine production, nasal mucosal fibroblasts and A549 bronchial epithelial cells were analyzed for the production of IL-8. Both nasal mucosal fibroblasts and bronchial epithelial cells produced significant amounts of IL-8 through stimulation of IL-1beta. Tea polyphenols were very effective in the inhibition of IL-8 production. Among the polyphenols tested, EGCG and ECG showed strong inhibitory activity in dose-dependent manners. EGC and EC showed moderate inhibition at 48 h culture, whereas (-)catechin was not effective. Production of IL-8 after stimulation by proinflammatory cytokines in both nasal fibroblasts and bronchial epithelial cells was significantly blocked by pretreatment with green tea polyphenols. (+info)
A new approach to managing oral manifestations of Sjogren's syndrome and skin manifestations of lupus.
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Sjogren's syndrome (SS) is an autoimmune disorder that affects the salivary glands, leading to xerostomia, and the lacrimal glands, resulting in xerophthalmia. Secondary SS is associated with other autoimmune disorders such as systemic rheumatic diseases and systemic lupus erythematosis (SLE), which can affect multiple organs, including the epidermis. Recent studies have demonstrated that green tea polyphenols (GTPs) possess both anti-inflammatory and anti-apoptotic properties in normal human cells. Epidemiological evidence has indicated that, in comparison to the United States, the incidence of SS, clinical xerostomia and lupus is considerably lower in China and Japan, the two leading green tea-consuming countries.Thus, GTPs might be responsible, in part, for geographical differences in the incidence of xerostomia by reducing the initiation or severity of SS and lupus. Consistent with this, molecular, cellular and animal studies indicate that GTPs could provide protective effects against autoimmune reactions in salivary glands and skin. Therefore, salivary tissues and epidermal keratinocytes could be primary targets for novel therapies using GTPs. This review article evaluates the currently available research data on GTPs, focusing on their potential application in the treatment of the oral manifestations of SS and skin manifestations of SLE. (+info)