Les polyphénols du thé et du cacao ont-ils des effets santé ?

The study of the role of dietary polyphenols in protecting disturbances, associated with development of degenerative diseases, has benefited both recent advances in food databases for epidemiological studies, and the growing number of randomized controlled clinical trials with foods rich in flavonoids. To date, available scientific data suggest that flavan-3-ols from green tea and cocoa can reduce the risk of type 2 diabetes and cardiovascular diseases. The most convincing evidence concern the beneficial effects of green tea on LDL-cholesterol and those of flavan-3-ols rich cocoa on endothelial function and insulin sensitivity. However, these results need to be confirmed in other prospective cohort studies and through long term controlled clinical trials. In general, the clinical evaluation of purified flavonoids is also necessary to identify the active compounds and effective doses. For other diseases such as cancer or neurodegenerative diseases, the low number of clinical studies coupled with strong variations in their results does not allow to conclude for now on the effects of the consumption of tea or cocoa rich flavan-3-ols.     

Green tea polyphenols induce differentiation and proliferation in epidermal keratinocytes

The most abundant green tea polyphenol, epigallocatechin-3-gallate (EGCG), was found to induce differential effects between tumor cells and normal cells. Nevertheless, how normal epithelial cells respond to the polyphenol at concentrations for which tumor cells undergo apoptosis is undefined. The current study tested exponentially growing and aged primary human epidermal keratinocytes in response to EGCG or a mixture of the four major green tea polyphenols. EGCG elicited cell differentiation with associated induction of p57/KIP2 within 24 h in growing keratinocytes, measured by the expression of keratin 1, filaggrin, and transglutaminase activity. Aged keratinocytes, which exhibited low basal cellular activities after culturing in growth medium for up to 25 days, renewed DNA synthesis and activated succinate dehydrogenase up to 37-fold upon exposure to either EGCG or the polyphenols. These results suggest that tea polyphenols may be used for treatment of wounds or certain skin conditions characterized by altered cellular activities or metabolism.     

Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma

The polyphenol epigallocatechin-3-gallate (EGCG), the principal mediator of the green tea, has been known to possess antitumor effect. The endothelin A receptor (ET(A)R)/endothelin-1 (ET-1) axis is overexpressed in ovarian carcinoma representing a novel therapeutic target. In this study, we examined the green tea and EGCG effects on two ovarian carcinoma cell lines, HEY and OVCA 433. EGCG inhibited ovarian cancer cell growth and induced apoptosis that was associated with a decrease in Bcl-X(L) expression and activation of caspase-3. Treatment with green tea or EGCG inhibited ET(A)R and ET-1 expression and reduced the basal and ET-1-induced cell proliferation and invasion. The EGCG-induced inhibitory effects were associated with a decrease of ET(A)R-dependent activation of the p42/p44 and p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinase pathway. Remarkably, EGCG treatment resulted in a lowering of basal and ET-1-induced angiogenesis and invasiveness mediators, such as vascular endothelial growth factor and tumor proteinase activation. Finally, in HEY ovarian carcinoma xenografts, tumor growth was significantly inhibited by oral administration of green tea. This effect was associated with a reduction in ET-1, ET(A)R, and vascular endothelial growth factor expression, microvessel density, and proliferation index. These results provide a novel insight into the mechanism by which EGCG, affecting multiple ET(A)R-dependent pathways, may inhibit ovarian carcinoma growth, suggesting that EGCG may be useful in preventing and treating ovarian carcinoma in which ET(A)R activation by ET-1 plays a critical role in tumor growth and progression.     

Modulation of endogenous antioxidant system by wine polyphenols in human disease

Numerous studies indicate that moderate red wine consumption is associated with a protective effect against all-cause mortality. Since oxidative stress constitutes a unifying mechanism of injury of many types of disease processes, it should be expected that polyphenolic antioxidants account for this beneficial effect. Nevertheless, beyond the well-known antioxidant properties of these compounds, they may exert several other protective mechanisms. Indeed, the overall protective effect of polyphenols is due to their large array of biological actions, such as free radical-scavenging, metal chelation, enzyme modulation, cell signalling pathways modulation and gene expression effects, among others. Wine possesses a variety of polyphenols, being resveratrol its most outstanding representative, due to its pleiotropic biological properties. The presence of ethanol in wine aids to polyphenol absorption, thereby contributing to their bioavailability. Before absorption, polyphenols must be hydrolyzed by intestinal enzymes or by colonic microflora. Then, they undergo intestinal and liver metabolism. There have been no reported polyphenol adverse effects derived from intakes currently associated with the normal diet. However, supplements for health-protection should be cautiously used as no level definition has been given to make sure the dose is safe. The role of oxidative stress and the beneficial effects of wine polyphenols against cardiovascular, cancer, diabetes, microbial, inflammatory, neurodegenerative and kidney diseases and ageing are reviewed. Future large scale randomized clinical trials should be conducted to fully establish the therapeutic use of each individual wine polyphenol against human disease.     

Epigallocatechin gallate-zinc oxide co-crystalline nanoparticles as an anticancer drug that is non-toxic to normal cells

Decreased uptake and cellular accumulation of zinc is a common characteristic in cancer of the liver, pancreas and prostate, because these malignant cells are intolerant to the physiological concentrations of zinc. A tea polyphenol, epigallocatechin-3-gallate (EGCG), can enhance the cytotoxicity of zinc ions to cancer, but the application of this is limited by the low stability of EGCG. In this work, we have prepared a material that can simultaneously preserve the EGCG stability and facilitate zinc uptake and accumulation in cancer cells, under conditions that are not harmful to normal cells. Thus, we co-crystallize zinc oxide with EGCG to obtain hybrid EGCG-ZnO crystalline nanoparticles of 16.5 ± 5.3 nm in diameter. The EGCG-ZnO particles effectively kill PC-3 prostate adenocarcinoma cells at concentrations that are not cytotoxic to normal cells, WI-38 human embryonic lung fibroblasts. The EGCG-ZnO particles are two times more cytotoxic against PC-3 cells than the standard ZnO particles. In PC-3 cells, the EGCG-ZnO particles are taken up by endocytosis, followed by lysosomal disruption to release zinc and EGCG into the cytoplasm, finally resulting in nuclear accumulation of zinc.

A tea polyphenol, epigallocatechin-3-gallate (EGCG), can enhance cytotoxicity of Zinc in cancer cells. Here we synthesize hybrid EGCG-ZnO nanoparticles that can kill PC-3 prostate cancer cells at concentrations that are not toxic to normal cells.     

Inhibition of MMP-9 by green tea catechins and prediction of their interaction by molecular docking analysis

Green tea polyphenolic catechins have been shown to prevent various types of diseases such as pulmonary hypertension (PAH), cancer and cardiac and neurological disorders. Matrix metalloproteinases (MMPs) play an important role in the development of PAH. The present study demonstrated that among the four green tea catechins (EGCG, ECG, EC and EGC), EGCG and ECG inhibit pro-/active MMP-9 activities in pulmonary artery smooth muscle cell culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-9 with the green tea catechins by computational methods. In silico molecular docking analysis revealed a strong interaction between pro-/active MMP-9 and EGCG/ECG, and galloyl group appears to be responsible for this enhanced interaction. The molecular docking studies corroborate our experimental observation that EGCG and ECG are mainly active in preventing both the proMMP-9 and MMP-9 activities.     

Green tea extract and (-)-epigallocatechin-3-gallate inhibit hypoxia- and serum-induced HIF-1alpha protein accumulation and VEGF expression in human cervical carcinoma and hepatoma cells

Green tea extract and its major component (-)-epigallocatechin-3-gallate (EGCG) exhibit antiangiogenic activities in various experimental tumor models. A growing body of evidence has established that hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream target, vascular endothelial growth factor (VEGF), play a critical role in tumor angiogenesis. In this study, we investigated the effect of green tea extract and EGCG on HIF-1alpha and VEGF expression in human cervical carcinoma (HeLa) and hepatoma (HepG2) cells. Our results showed that green tea extract and EGCG significantly inhibited hypoxia- and serum-induced HIF-1alpha protein accumulation in these cancer cells but had no effects on HIF-1alpha mRNA expression. Suppression of HIF-1alpha protein by green tea extract and EGCG also resulted in a drastic decrease in VEGF expression at both mRNA and protein levels. The mechanisms of green tea extract and EGCG inhibition of hypoxia-induced HIF-1alpha protein accumulation seem to involve the blocking of both phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2 signaling pathways and the enhancing of HIF-1alpha protein degradation through the proteasome system. In addition, green tea extract and EGCG inhibited serum-induced HIF-1alpha protein and VEGF expression by interfering with the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathways, which play a crucial role in the protein translational machinery cascade. Functionally, green tea extract and EGCG abolished both chemoattractant- and hypoxia-stimulated HeLa cell migration. Our data suggested that HIF-1alpha/VEGF function as therapeutic target for green tea extract and EGCG in the context of cancer chemoprevention and anticancer therapy.     

Cancer therapy combination: green tea and a phosphodiesterase 5 inhibitor?

The major constituent of green tea, (–)-epigallocatechin-3-O-gallate (EGCG), has been shown to have cancer-preventive and therapeutic activities. Numerous molecular targets for EGCG have been proposed, but the mechanisms of its anticancer activities are not clearly understood. In this issue of the JCI, Kumazoe et al. report that EGCG activates 67-kDa laminin receptor (67LR), elevates cGMP levels, and induces cancer cell apoptosis. Furthermore, a phosphodiesterase 5 inhibitor, vardenafil, synergizes with EGCG to induce cancer cell death. This is a provocative observation with important implications for cancer therapy. It also raises several issues for further investigation, such as the mechanism by which EGCG specifically activates 67LR. Green tea, a popular beverage made from the leaves of the plant Camellia sinensis, has been studied for the past 25 years for its cancer-preventive and therapeutic activities. Green tea preparations have been shown to inhibit tumorigenesis in animal models for cancers of the lung, oral cavity, esophagus, stomach, small intestine, colon, skin, liver, pancreas, bladder, prostate, and mammary glands (reviewed in ref. 1). Most of the inhibitory activities have been attributed to the major and characteristic tea polyphenol, (–)-epigallocatechin-3-O-gallate (EGCG) (Figure ​(Figure1).1). EGCG is an antioxidant with strong binding affinities to biological molecules, but has only limited systemic bioavailability when ingested orally. After consumption of the equivalent of two or three cups of green tea, the peak plasma levels of EGCG are usually 0.2–0.3 μM. With high oral doses of tea polyphenols (e.g., 800 mg EGCG per day), a peak plasma level as high as 3.5 μM has been reported (2). In black tea, the levels of EGCG are only 10%–25% those of green tea because the monomeric tea polyphenols are polymerized to form theaflavins and thearubigins, which have little or no systemic bioavailability. Thus, consumption of green tea is frequently associated with decreased risk for gastrointestinal tract cancers, whereas intake of black tea is rarely associated with such a benefit (3). Open in a separate windowFigure 1Proposed mechanisms of anticancer action of EGCG.The mechanism by which EGCG exerts its antitumor actions is unknown, but may involve one or more of the actions illustrated. EGCG can act as an antioxidant, reducing ROS and inhibiting cancer development, and paradoxically may promote the production of ROS in cancer cells and induce apoptosis. EGCG is also known to bind and modulate the activities of enzymes, receptors, and signaling molecules that affect cell growth and proliferation. Activation of 67LR by EGCG and inhibition of PDE5 activity by its inhibitors synergistically induce cancer cell apoptosis (8). DNMT1, DNA, methyltransferase 1; DHFr, dihydrofolate reductase; HGFR, HGF receptor; Bcl-2, B cell CLL/lymphoma 2; GRP78, glucose-regulated protein 78 kDa; Pin1, peptidyl cis/trans isomerase.     

NO and HNO donors,nitrones, and nitroxides: Past,present, and future

The biological effects attributed to nitric oxide (^?NO) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age‐related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N‐O bond enabled the development of several classes of compounds with potential clinical interest, among which ^?NO and HNO donors, nitrones, and nitroxides are of particular importance. Although primarily studied for their application as cardioprotective agents and/or molecular probes for radical detection, continuous efforts have unveiled a wide range of pharmacological activities and, ultimately, therapeutic applications. These efforts are of particular significance for diseases in which oxidative stress plays a key pathogenic role, as shown by a growing volume of in vitro and in vivo preclinical data. Although in its early stages, these efforts may provide valuable guidelines for the development of new and effective N‐O‐based drugs for age‐related disorders. In this report, we review recent advances in the chemistry of NO and HNO donors, nitrones, and nitroxides and discuss its pharmacological significance and potential therapeutic application.     

Effects of the main green tea polyphenol epigallocatechin-3-gallate on cardiac involvement in patients with AL amyloidosis

Background  

Amyloid light chain (AL) amyloidosis is a rare disease with poor prognosis and limited therapeutic alternatives. Recently, one clinical case with cardiac involvement, as well as a compelling evidence of green tea polyphenol, epigallocatechin-3-gallate (EGCG), inducing the formation of benign aggregation products that do not polymerize into fibrils were published. This is a report of the cardiac effects of green tea consumption in these patients.     

Total polyphenol intake estimated by a modified Folin-Ciocalteu assay of urine

BACKGROUND: Plant polyphenols have been studied largely because of the possibility that they might underlie the protective effects afforded by fruit and vegetable intake against cancer and other chronic diseases. Measurement of polyphenol content excreted in urine as an indicator of polyphenol consumption may offer a routine screening method that could be used for these pathologies. METHODS: Thirty-six healthy volunteers each received 2 interventions, one with a polyphenol-rich food (cocoa beverage) and one with a polyphenol-free food (milk) as a control, in a randomized cross-over design with 1-week intervals. The total polyphenol content excreted in urine during the 6 h after consumption of the test meals was measured by a modified Folin-Ciocalteu assay after sample cleanup by solid-phase extraction. RESULTS: The mean (SD) concentrations of polyphenols excreted in the urine 6 h after consumption of the test meals differed significantly: 140.95 (49.27) mg catechin/g of creatinine after the polyphenol-rich meal vs 90.43 (46.07) mg catechin/g of creatinine after the control meal (P <0.05). CONCLUSIONS: This method allows analysis of a large number of samples per day, which is ideal for use in epidemiologic studies and may enable estimation of polyphenol consumption and determination of their possible role in preventing of certain pathologies, such as cancer, cardiovascular and degenerative diseases.     

Health benefits of resveratrol: Evidence from clinical studies

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5′-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH–associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.     

Molecular chaperones: Toward new therapeutic tools

Molecular chaperones (or heat shock proteins) are evolutionarily conserved and essential proteins that play a key role in cell survival through cytoprotective mechanisms. Despite their possible clinical applications, the understanding of these structures is still quite limited. The aim of the present study is to review the literature to understand the physiological importance, implication in various diseases (especially in cancer and neurodegenerative diseases), possible applicability, and future prospects of heat shock proteins. The cytoprotective mechanisms of molecular chaperones can be co-opted by oncogenic processes favoring tumor growth, invasion, evasion of apoptosis, and metastasis, thus making inhibitors to these molecules possible therapeutic options for cancer patients. However, there is also evidence showing that upregulation of heat shock proteins can have an antineoplastic effect through immunomodulatory activity. This is why chaperones have already been investigated for conventional chemotherapy under specific conditions, yielding interesting results. The induction of heat shock protein activity is also of potential benefit in many other diseases where structural and functional preservation of proteins may enhance cell survival, including neurodegeneration, trauma, stroke, and cardiovascular disease. In addition, the immune properties of chaperones can potentially be exploited for such diseases as diabetes, atherosclerosis, and other chronic inflammatory conditions. Thus, continuing efforts to clarify the role of chaperones may guide the development of new therapeutic modalities capable of minimizing the impact of diseases such as cancer, heart disease, and diabetes as well as obtaining better results in neurological conditions currently lacking alternative treatments.     

Stress influence on genesis,onset and maintenance of cardiovascular diseases: literature review

BACKGROUND: Recent mortality profiles in Brazil show that circulatory diseases are the leading cause of death in Brazil. These disorders contribute to 34% of deaths, with 50% of those deaths occurring in people under 50 years of age, that is, in people who are still active in the workforce. We assume that the growing incidence of cardiovascular diseases has occurred as the globalization of Brazil continues and brings with it the associated health risk factors of modern lifestyles, including stress. AIM: This paper reports the evidence on the influence of stress in the development, onset and progress of cardiovascular diseases. We aim to define the concept of stress and to point systematically to the interrelationships between its emotional and bodily manifestations through a discussion of the history and study of stress. We then suggest that factors leading to the experience of stress in Brazil are no different than in any other modern nation. We further offer a perspective on nursing interventions currently undertaken in Brazil in both hospital and community settings, with their more recent emphasis on health promotion and prevention. METHODS: An extensive literature review was undertaken. The data presented here were selected from reviews and clinical studies described in MEDLINE, LILACS, SciELO databases, as well as in the classical literature. We also refer to the current Brazilian literature on the prevalence of cardiovascular diseases and their associated risk factors. CONCLUSIONS: The incidence of cardiovascular diseases in Brazil is rising. Because of the globalization of Brazilian society, with its consequent competitiveness and accelerated modern lifestyles, Brazilians are no less immune to the usual health risk factors associated with cardiovascular diseases. Stresses associated with a modern lifestyle, however, are emerging as a new and major risk for developing cardiovascular diseases in Brazil.     

Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-beta1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.     

Chronic Respiratory Diseases and Neurodegenerative Disorders: A Primer for the Practicing Clinician

Chronic respiratory disorders represent a world epidemic. Their incidence and prevalence in the world population is increasing, and especially among elderly subjects, they are commonly associated with other pathologies, often generating a status of high clinical complexity. Neurology, internal medicine, and pneumology specialists should be aware of the common background of these disorders in order to treat correctly the patient''s comorbid state and optimize the treatment considering potential overlaps. In this review, we aimed to focus on the relationships between chronic respiratory disorders and chronic neurodegenerative diseases at different levels; we review the shared risk factors and the interactions between disorders, the indications to explore respiratory function in neurodegenerative diseases, pathology-pathology and drug-pathology interactions in patients affected by both chronic neurologic and respiratory diseases.     

Reading the tea leaves: anticarcinogenic properties of (-)-epigallocatechin-3-gallate

Green tea is an extremely popular beverage worldwide. Derivatives of green tea, particularly (-)-epigallocatechin-3-gallate (EGCG), have been proposed to have anticarcinogenic properties based on preclinical, observational, and clinical trial data. To summarize, clarify, and extend current knowledge, we conducted a comprehensive search of the PubMed database and other secondary data sources, as appropriate, regarding the chemopreventive potential of EGCG. Apparently, EGCG functions as an antioxidant, preventing oxidative damage in healthy cells, but also as an antiangiogenic agent, preventing tumors from developing a blood supply needed to grow larger. Furthermore, EGCG may stimulate apoptosis in cancerous cells by negatively regulating the cell cycle to prevent continued division. Finally, EGCG exhibits antibacterial activity, which may be implicated in the prevention of gastric cancer. Although in vitro research of the anticarcinogenic properties of EGCG seems promising, many diverse and unknown factors may influence its in vivo activity in animal and human models. Some epidemiological studies suggest that green tea compounds could protect against cancer, but existing data are inconsistent, and limitations in study design hinder full interpretation and generalizability of the published observational findings. Several clinical trials with green tea derivatives are ongoing, and further research should help to clarify the clinical potential of EGCG for chemoprevention and/or chemotherapy applications.     

Medicinal benefits of green tea: part II. review of anticancer properties

Currently there is wide interest in the medicinal benefits of green tea (Camellia sinensis). Tea is one of the most widely consumed beverages in the world, and extracts of tea leaves are also sold as dietary supplements. Green tea extracts contain a unique set of catechins that possess biologic activity in antioxidant, antiangiogenesis, and antiproliferative assays that are potentially relevant to the prevention and treatment of various forms of cancer. With the increasing interest in the health properties of tea and a significant rise in their scientific investigation, it is the aim of this review to summarize recent findings on the anticancer and medicinal properties of green tea, focusing on the biologic properties of the major tea catechin, (-)-epigallocatechin and its antitumor properties.