Catechins Are Bioavailable in Men and Women Drinking Black Tea throughout the Day

Warden, Beverly A.; Smith, Lametta S.; Beecher, Gary R.; Balentine, Douglas A.; Clevidence, Beverly A.

doi:10.1093/jn/131.6.1731

Cited by 220 publications

(122 citation statements)

References 35 publications

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“…However, the effect appears at relatively high concentrations. The level of availability of catechins has been confirmed at lower concentrations (15,3). The plasma concentrations and doses presented in recent studies were much lower than that presented as effective in the present study.…”

Section: Discussionsupporting

confidence: 59%

The effect of epigallocatechin gallate on intestinal motility in mice

Ceregrzyn

Kuwahara

2003

Environ Health Prev Med

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Objectives: The epigallocatechin-3-gallate (EGCg) that is present in human diet originates mainly from tea leaves. Catechins have a number of possible application as medicines, however, there is no consistent evidence showing their influence on the gastrointestinal tract. Thus, the aim of the present study was to investigate the effect of EGCg on the motility of the murine isolated intestine.Methods: Segments of jejunum submerged in Krebs buffer were exposed to EGCg and the response was recorded under isometric conditions.Results: EGCg induced a dose-dependent inhibition of spontaneous activity in the jejunum. EGCg induced a decrease in the amplitude and frequency of jejunal contractions. Moreover, the rythmicity of spontaneous activity was altered in the presence of EGCg. A significant effect of EGCg was observed in the presence of 10 −4 M. The effect of EGCg was in part inhibited by pretreatment with methylene blue (guanylate cyclase inhibitor), while tetrodotoxin, (sodium channel blocker), L-nitro arginine methyl ester (nitric oxide synthase inhibitor), and N-ethylmaleimide (adenylate cyclase inhibitor) showed no effect.Conclusions: The results of the present study suggest that EGCg inhibits the motility of the jejunum by direct action on smooth muscle cells where a guanylate cyclase-dependent mechanism may be partly involved.

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Section: Discussionsupporting

confidence: 59%

The effect of epigallocatechin gallate on intestinal motility in mice

Ceregrzyn

Kuwahara

2003

Environ Health Prev Med

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“…At the same time the TEER values decreased and the mannitol values increased, consistent with opening of the tight junctions. Maybe this is what actually happens in vivo, providing the low extent of systemic absorption of the tea flavonoids reported (Baba et al, 2000;Chow et al, 2001;Warden et al, 2001). The balance between absorption and efflux may also shift depending on the presence of other flavonoids or components in the diet.…”

Section: Discussionmentioning

confidence: 92%

“…The oral bioavailability of tea flavonoids has been suggested to be low in rats (Chen et al, 1997;Zhu et al, 2000) as well as in humans (Yang et al, 1998;Baba et al, 2000;Chow et al, 2001;Warden et al, 2001).…”

mentioning

confidence: 99%

Cellular Uptake and Efflux of the Tea Flavonoid (-)Epicatechin-3-gallate in the Human Intestinal Cell Line Caco-2

Vaidyanathan

Walle²

2003

J Pharmacol Exp Ther

276

234

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(Ϫ)-Epicatechin gallate (ECG) is one of the flavonoids in green tea, which has been demonstrated to have cancer-preventive properties in many model systems. However, the extent and mechanisms of accumulation of these flavonoids in cells is unknown. The objectives of this study were to determine the accumulation of ECG by the intestinal epithelial cell Caco-2 and to characterize the transport mechanism involved. The cells were exposed to ECG Ϯ various transport inhibitors and incubated at 37°C. Absorbed flavonoids were extracted and quantified by high-performance liquid chromatography. The uptake of ECG included a nonsaturable initial rapid process as well as a much slower saturable process. The saturable ECG uptake by the Caco-2 cells was sodium-independent but clearly dependent on a pH gradient. Phloretin and benzoic acid, inhibitors of the monocarboxylate transporter (MCT), significantly reduced ECG uptake. The uptake of ECG in the Caco-2 cells increased 2-fold in the presence of 50propionic acid (MK-571), suggesting the involvement of multidrugassociated protein (MRP)2 in efflux of ECG. This was confirmed using Madin-Darby canine kidney cells transfected with MRP2. Also P-glycoprotein was responsible for some ECG efflux. MK-571 also caused a dramatic increase in ECG accumulation in Chinese hamster ovary cells, suggesting that ECG was also a substrate for MRP1. Together, these observations demonstrate important roles of membrane transporters, i.e., MCT, MRP2, Pglycoprotein, and MRP1, in the cellular accumulation and potential effects of ECG.

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“…40 A later report indicates that compound 1 accumulates in a linear fashion in plasma, reaching a concentration of 50.6 nM 24 h after consuming four doses of various black tea preparations. 41 It is clear that this plasma concentration of 1 is far below that required to activate HIF-1 in vitro. However, the following factors can significantly increase the bioavailability of 1 and reduce the actual amount needed to activate HIF-1 in humans.…”

Section: Ascorbate and Trolox ® Inhibit Ecg (1)-induced Hif-1 Activationmentioning

confidence: 99%

Hypoxia-Inducible Factor-1 Activation by (−)-Epicatechin Gallate: Potential Adverse Effects of Cancer Chemoprevention with High-Dose Green Tea Extracts

Zhou

Kim

et al. 2004

J. Nat. Prod.

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Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that induces oxygen-regulated genes in response to reduced oxygen conditions (hypoxia). Expression of the oxygen regulated HIF-1α subunit correlates positively with advanced disease stages and poor prognosis in cancer patients. Green tea catechins are believed to be responsible for the cancer chemopreventive activities of green tea. We found that (−)-epicatechin-3-gallate (ECG, 1), one of the major green tea catechins, strongly activates HIF-1 in T47D human breast carcinoma cells. Among the green tea catechins tested, 1 demonstrated the strongest HIF-1 inducing activity while (−)-epigallocatechin-3-gallate (EGCG, 2), was significantly less active. However, 2 is relatively unstable in the in vitro system studied. Compound 1 also increases the expression of HIF-1 target genes including GLUT-1, VEGF, and CDKN1A. In T47D cells, 1 induces nuclear HIF-1α protein without affecting HIF-1α mRNA. Both the induction of HIF-1α protein and activation of HIF-1 by 1 can be blocked by iron and ascorbate, indicating that 1 may activate HIF-1 through the chelation of iron. These results suggest that intended cancer chemoprevention with high-dose green tea extracts may be compromised, by the ability of tea catechins to promote tumor cell survival pathways associated with HIF-1 activation.Rapid tumor growth often outstrips the ability of blood vessels to supply oxygen and nutrients, leaving many regions inside solid tumors low in oxygen (hypoxia). In cancer patients, the extent of tumor hypoxia correlates positively with advanced disease stages, poor prognosis, and treatment resistance. 1 Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in hypoxia activated gene expression. 2 In tumor cells, HIF-1 activates the transcription of genes involved in anaerobic metabolism, angiogenesis, survival, invasion/metastasis and treatment resistance, thus promoting cellular This study investigates the effects of green tea catechins and related compounds on HIF-1 activity in vitro. Among the compounds tested [1-4, (+)-catechin (5), and gallic acid (6)], only catechins that contain the 3-gallate moiety (1 and 2) activate HIF-1 in a T47D cellbased reporter assay. In addition, 1 inhibits HIF-1 activation under hypoxic conditions. Apart from one hydroxyl group, 1 and 2 are structurally identical. However, 2 is chemically less stable than 1. The focus of this study is the regulation of HIF-1 activity by ECG (1). The pathways and mechanisms involved in HIF-1 activation have been extensively studied. 1,2,9 In the presence of oxygen, the HIF-1α subunit is prolyl hydroxylated, recognized by an E3 ubiquitin ligase complex that contains the von Hippel-Lindau tumor suppressor protein (pVHL), polyubiquitylated, and degraded by the 26S proteosome. [15][16][17] The HIF-1α protein is also asparaginyl hydroxylated to prevent HIF-1 activation. 18 At reduced cellular oxygen levels, inhibition of HIF-1α protein prolyl hydroxylation and degradation leads to an ...

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Catechins Are Bioavailable in Men and Women Drinking Black Tea throughout the Day

Cited by 220 publications

References 35 publications

The effect of epigallocatechin gallate on intestinal motility in mice

The effect of epigallocatechin gallate on intestinal motility in mice

Cellular Uptake and Efflux of the Tea Flavonoid (-)Epicatechin-3-gallate in the Human Intestinal Cell Line Caco-2

Hypoxia-Inducible Factor-1 Activation by (−)-Epicatechin Gallate: Potential Adverse Effects of Cancer Chemoprevention with High-Dose Green Tea Extracts

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