Catechins are bioavailable in men and women drinking black tea throughout the day.

Tea consumption has been associated with reduced risk of both cancer and cardiovascular disease in population studies, but clinical data demonstrating bioavailability of the individual catechins and other polyphenolic components of tea are limited. This study assessed the apparent bioavailability of the prominent catechins from black tea in humans drinking tea throughout the day. After 5 d of consuming a low flavonoid diet, subjects drank a black tea preparation containing 15.48, 36.54, 16.74, and 31.14 mg of (-)-epigallocatechin (EGC), (-)-epicatechin (EC), (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG), respectively, at four time points (0, 2, 4 and 6 h). Blood, urine and fecal specimens were collected over a 24- to 72-h period and catechins were quantified by HPLC with coularray detection. Plasma concentrations of EGC, EC and EGCG increased significantly relative to baseline (P < 0.05). Plasma EGC, EC and EGCG peaked after 5 h, whereas ECG peaked at 24 h. Urinary excretion of EGC and EC, which peaked at 5 h, was increased relative to baseline amounts (P < 0.05) and fecal excretion of all four catechins was increased relative to baseline (P < 0.05). Approximately 1.68% of ingested catechins were present in the plasma, urine and feces, and the apparent bioavailability of the gallated catechins was lower than the nongallated forms. Thus, catechins were bioavailable. However, unless they are rapidly metabolized or sequestered, the catechins appeared to be absorbed in amounts that were small relative to intake.

Role of medicinal plants, herbs, and spices in protecting human health.

The body of knowledge about plants, herbs, and spices and their respective and collective roles in promoting human health is modest. Flavonoids in tea and anthocyanins in tart cherries were presented as examples of how to move forward in understanding active compounds. Dietary compounds, their roles in maintaining human health, and their interactions with established nutrients were determined to be short-term research priorities.

Effects of chemoprotective agents on the metabolic activation of the carcinogenic arylamines PhIP and 4-aminobiphenyl in human and rat liver microsomes.

Carcinogenic aromatic amines, including the heterocyclic amines, may pose a significant health risk to humans. To determine the potential for chemoprotective intervention against the carcinogenicity of these arylamines and to better understand their mechanism of action, a range of agents, most of them natural dietary constituents, was examined in vitro for their ability to modulate the N-hydroxylation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 4-aminobiphenyl (ABP), an initial step in their bioactivation. Experiments were conducted with rat and human liver microsomes. The agents (diallyl sulfide, indole-3-carbinol, alpha-angelicalactone, cafestol/kahweol palmitates, cafestol, kahweol, benzylisothiocyanate, genistin, formononetin, daidzin, equol, biochanin A, Oltipraz, tannic acid, quercetin, ethoxyquin, green tea, and black tea) comprised a variety of chemical classes that included sulfur-containing compounds, antioxidants, flavonoids, phytoestrogens, diterpenes, and polyphenols. Several of these agents, quercetin, ethoxyquin, and black tea, were found to strongly inhibit PhIP N-hydroxylation in rat liver microsomes, resulting in a nearly 85-90% decrease in activity at 100 microM or 0.2%. Tannic acid and green tea, in addition to these agents, were also strong inhibitors of ABP N-hydroxylation. In human liver microsomes, each of these agents was strongly inhibitory (approx 85-95% at 100 microM or 0.02%) of PhIP and ABP N-hydroxylation. Theaflavins and polyphenols were judged to be the primary inhibiting components in the teas, the theaflavins showing the most potent effect. These results demonstrate that chemoprotective agents can inhibit the bioactivation of carcinogenic arylamines, and this is likely to be one of the mechanisms of protection.

Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of estradiol and estrone.

Administration of 0.5 or 1% lyophilized green tea (5 or 10 mg tea solids per ml, respectively) as the sole source of drinking fluid to female Long-Evans rats for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 30-37%, 15-27% and 26-60%, respectively. Oral administration of 0.5% lyophilized green tea to female CD-1 mice for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 33-37%, 12-22% and 172-191%, respectively. The in vitro addition of a green tea polyphenol mixture, a black tea polyphenol mixture or (-)-epigallocatechin gallate inhibited rat liver microsomal glucuronidation of estrone and estradiol in a concentration-dependent manner and their IC50 values for inhibition of estrogen metabolism were approximately 12.5, 50 and 10 microg/ml, respectively. Enzyme kinetic analysis indicates that the inhibition of estrone glucuronidation by 10 microM (-)-epigallocatechin gallate was competitive while inhibition by 50 microM (-)-epigallocatechin gallate was noncompetitive. Similarly, several flavonoids (naringenin, hesperetin, kaempferol, quercetin, rutin, flavone, alpha-naphthoflavone and beta-naphthoflavone) also inhibited rat liver microsomal glucuronidation of estrone and estradiol to varying degrees. Naringenin and hesperetin displayed the strongest inhibitory effects (IC50 value of approximately 25 microM). These two hydroxylated flavonoids had a competitive mechanism of enzyme inhibition for estrone glucuronidation at a 10 microM inhibitor concentration and a predominantly noncompetitive mechanism of inhibition at a 50 microM inhibitor concentration.

Effect of tea extracts, polyphenols, and epigallocatechin gallate on azoxymethane-induced colon cancer.

Studies were conducted to determine the chemopreventive efficacy of several types of tea extracts on azoxymethane-induced colon cancer in male F344 rats. After determining the maximally tolerated dosage of the tea products, their effect in a colon cancer model was investigated. Groups of 36 male F344 rats received 2 subcutaneous doses of 15 mg/kg azoxymethane (AOM) at Weeks 6 and 7. Experimental groups also received as drinking fluids 3600 ppm of black or green tea extracts, 1800 ppm of EGCG, or 1800 ppm of black or green tea polyphenols beginning at 5 weeks of age. Additional groups drank a lower dose of 360 ppm of the five tea products. The experiments were terminated 43 weeks after the first tea exposure. No evidence of toxicity was observed since the body weight gain of all groups was similar. The rats given AOM had carcinoma of the small intestine and of the colon, classified histologically as in situ carcinoma, exophytic, invasive, and Peyer's patch carcinoma. In the small intestine, most of the neoplasms were classified as invasive, but in the colon, most were exophytic. The various tea products failed to produce a significant difference in the incidence of the several types of colon and small intestine carcinoma. The multiplicity of colon cancers ranged from 1.2-2.8 in all groups. The group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the control group on AOM and water. Also, the group on 3600 ppm of green tea had a significantly higher tumor multiplicity than the group on 360 ppm. The tea products did not affect the development aspects of the tumors in most groups. The mechanisms underlying these findings rest on the fact that azoxymethane is metabolized mainly by cytochrome P450 2E1, and this enzyme system is not affected by tea.

Inhibition of PhIP mutagenicity by catechins, and by theaflavins and gallate esters.

Aqueous solutions of gallic acid, methyl gallate, catechins, theaflavins and tannic acid were tested for inhibition of the mutagenicity of PhIP in the Salmonella typhimurium TA98 assay with an S9 fraction from the liver of rats induced with alpha-naphthoflavone and phenobarbital. The IC50S were in the 80-250 microM range for the gallated catechins, theaflavins and tannic acid. No inhibition could be found with these compounds when a direct acting mutagen was used. This indicates that the anti-mutagenic properties of these phenolic compounds may be due to their inhibition of the cytochrome P-450 enzymes.

Effects of theaflavins on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis.

The purpose of this experiment was to compare the inhibitory effects of the polyphenol fraction of black tea, theaflavins (TF), the polyphenol fraction of green tea, and (-)-epigallocatechin-3-gallate (EGCG) in the rat esophageal tumor model. The tea fractions were administered in the drinking water at concentrations of 360 and 1,200 ppm for two weeks before administration of the esophageal carcinogen N-nitrosomethylbenzylamine (NMBA). NMBA was administered subcutaneously in 10% dimethyl sulfoxide three times weekly for five weeks. Additional groups of rats received only vehicle and plain drinking water or vehicle and drinking water containing 1,200 ppm of each tea fraction. Twenty-five weeks after NMBA administration began, the experiment was terminated and esophagi were excised and scored for tumors. Rats that were not dosed with NMBA had no tumors. Rats treated with NMBA only had an esophageal tumor incidence of 100% and a multiplicity of 3.3 +/- 0.4 tumors/rat. The proportion of rats developing tumors was not significantly reduced by any of the four tea fractions at the concentrations tested. However, the 1,200 ppm concentrations of each tea fraction in the drinking water produced some reduction in esophageal tumor multiplicity, although only TF significantly reduced tumor multiplicity compared with rats treated with NMBA only. The rates of esophageal tumor formation were significantly reduced at 360 and 1,200 ppm by TF and EGCG.

Inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) mutagenicity by black and green tea extracts and polyphenols.

Solutions of lyophilized preparations of standard black and green tea extracts were made and tested over a range of six concentrations as inhibitors of the mutagenicity caused by the fool mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the Salmonella typhimurium TA98 assay containing S9 fraction from rats induced with alpha-naphthoflavone and phenobarbital. Extracts of both black and green tea were equally good inhibitors of mutagenicity. Purified polyphenols were prepared from tea extracts by solvent extraction. The polyphenols of black tea were more potent inhibitors of mutagenicity than the polyphenols of green tea. These findings suggest that black tea may have similar health-promoting properties to those reported previously for green tea.

Analysis of plasma and urinary tea polyphenols in human subjects.

Tea has been shown to inhibit chemically induced tumorigenesis in many animal models, but the effects of tea consumption on human carcinogenesis are not conclusive. In order to develop biomarkers for tea consumption, we developed methods for the analysis of tea polyphenols in human plasma and urine samples using HPLC with the coulochem electrode array detection system. (-)-Epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epicatechin (EC) are the major polyphenols in green tea. Most of the tea polyphenols were in their conjugated forms in the plasma and urine. The samples were incubated with a mixture of beta-glucuronidase and sulfatase to generate the free form of tea polyphenols. After extraction into ethyl acetate and separation by reversed-phase chromatography, EGCG, EGC, and EC were identified on the basis of their retention times and electrochemical characteristics. Due to the high selectivity of the detection mode, interference was minimized. Good quantitative relationships were established for a large concentration range of tea polyphenols. The limits of detection for EGCG, EGC, ECG, and EC were from 0.5 to 1.5 ng/ml of plasma or urine sample. After ingestion of 1.2 g of decaffeinated green tea in warm water, the plasma samples collected at 1 h from 4 human volunteers contained 46-268 ng/ml of EGCG, 82-206 ng/ml of EGC, and 48-80 ng/ml of EC. ECG was not detected in plasma samples. The maximum urinary excretion of EGC and EC occurred at 3-6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of exercise and fasting on the myocardial protein and lipid metabolism in experimental bacterial myocarditis.

A generally nonlethal Salmonella typhimurium infection in weanling rats produced bacterial myocarditis and myocardial hyperplasia. Myocardial lesions were characterized by focal infiltrates of inflammatory cells (predominantly mononuclear), segmental myocyte necrosis, and incipient fibrosis. Although bacterial infections are infrequently associated with myocarditis, the S. typhimurium infection in young rats produced a new experimental model of diffuse myocardial inflammatory foci. Biochemical changes in the myocardium included great increases in total myocardial contents of protein (23%), RNA (39%) and DNA (43%) and several lipid fractions (35-55%) as well as in tissue activities of acid hydrolases, such as cathepsin D (124%) and beta-glucuronidase (135%), all of which contrasted with the relatively limited areas of histologic involvement (1.5%). To study the effects of additional stress in this model infection, some rats were exercised by forced running in wheels for 2 hours and others were fasted for 24 hours before samples were obtained. The short period of forced exercise in this infection caused an additional increase of myocardial protein content (47%) but with no additional change in histology. The expected fasting-induced degradation of protein as well as an infection-associated increase in myocardial lipids were each prevented when rats were fasted during ongoing acute infection. Protein degradation, as reflected by heightened acid hydrolase activities, seemed to occur at a similar rate regardless of other stresses, whereas the rate of myocardial protein synthesis appeared to be alterable.