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Journal Article

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

01 Dec 2000-Pharmacological Reviews (American Society for Pharmacology and Experimental Therapeutics)-Vol. 52, Iss: 4, pp 673-751
TL;DR: Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional, and suggestions are made where such possibilities may be worth pursuing.
Abstract: Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.
Citations
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Journal ArticleDOI
TL;DR: The nature and contents of the various polyphenols present in food sources and the influence of agricultural practices and industrial processes are reviewed, and bioavailability appears to differ greatly between the variousPolyphenols, and the most abundantpolyphenols in the authors' diet are not necessarily those that have the best bioavailability profile.

6,842 citations


Cites background from "The Effects of Plant Flavonoids on ..."

  • ...Furthermore, polyphenols, which constitute the active substances found in many medicinal plants, modulate the activity of a wide range of enzymes and cell receptors (1)....

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Journal ArticleDOI
TL;DR: Several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

3,630 citations


Cites background from "The Effects of Plant Flavonoids on ..."

  • ...However, this family of compounds has a diverse range of activities in mammalian cells [14, 20] and in vivo confirmation of their side effects would be necessary for a full evaluation of their practical usefulness in the field of modern medicine [29] ....

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  • ...Given that the selectivity of flavonoids for eukaryotic enzymes appears to vary from compound to compound [15, 20] , such a study would need to assess the toxicity of these phytochemicals on an individual basis....

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  • ...[20] ....

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  • ...The diverse range of cell functions affected by flavonoids in eukaryotic systems is well documented [10, 20] ....

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  • ...[17, 18] , isoflavones [10] , chalcones [13, 19] , flavanones [10, 13] , flavones [10] , flavonols [10] , flavanon-3-ols [13] , anthocyanidins [13, 20] , flavan-3-ols [10, 13] , proanthocyanidins (occur as dimers, trimers, tetramers and pentamers; R = 0, 1, 2 or 3 flavan-3-ol structures) [13] , flavans [13] , flavan-3,4-diols [13] and dihydrochalcones [13] ....

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Journal ArticleDOI
11 Sep 2003-Nature
TL;DR: The potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating Sirt1-dependent deacetylation of p53.
Abstract: In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD(+), and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators.

3,572 citations

Journal ArticleDOI
TL;DR: Phenolic compounds, ubiquitous in plants are an essential part of the human diet, and are of considerable interest due to their antioxidant properties as mentioned in this paper, and their structures may range from a simple phenolic molecule to a complex high-molecular weight polymer.

2,723 citations

Journal ArticleDOI
TL;DR: It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how (poly)phenol molecules interact with human physiological and pathological processes.
Abstract: Human intervention trials have provided evidence for protective effects of various (poly)phenol-rich foods against chronic disease, including cardiovascular disease, neurodegeneration, and cancer. While there are considerable data suggesting benefits of (poly)phenol intake, conclusions regarding their preventive potential remain unresolved due to several limitations in existing studies. Bioactivity investigations using cell lines have made an extensive use of both (poly)phenolic aglycones and sugar conjugates, these being the typical forms that exist in planta, at concentrations in the low-μM-to-mM range. However, after ingestion, dietary (poly)phenolics appear in the circulatory system not as the parent compounds, but as phase II metabolites, and their presence in plasma after dietary intake rarely exceeds nM concentrations. Substantial quantities of both the parent compounds and their metabolites pass to the colon where they are degraded by the action of the local microbiota, giving rise principally to small phenolic acid and aromatic catabolites that are absorbed into the circulatory system. This comprehensive review describes the different groups of compounds that have been reported to be involved in human nutrition, their fate in the body as they pass through the gastrointestinal tract and are absorbed into the circulatory system, the evidence of their impact on human chronic diseases, and the possible mechanisms of action through which (poly)phenol metabolites and catabolites may exert these protective actions. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes.

1,968 citations


Cites background from "The Effects of Plant Flavonoids on ..."

  • ...While a number of in vitro experiments have suggested that (poly)phenols may influence carcinogenesis and tumor development (61, 126, 306, 356, 470), very few clinical trials have been conducted regarding the role of (poly)phenols in cancer prevention, incidence, or mortality....

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References
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Additional excerpts

  • ...independent of transition metal ions (Beckman et al., 1990)....

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Journal ArticleDOI
TL;DR: The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes.
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6,464 citations

Journal ArticleDOI
01 Nov 1984-Nature
TL;DR: Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.
Abstract: There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.

5,712 citations