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Polyphenols are found ubiquitously in plants and their regular consumption has been associated with a reduced risk of a number of chronic diseases, including cancer, cardiovascular disease (CVD) and neurodegenerative disorders. Rather than exerting direct antioxidant effects, the mechanisms by which polyphenols express these beneficial properties appear to involve their interaction with cellular signaling pathways and related machinery that mediate cell function under both normal and pathological conditions. We illustrate that their interactions with two such pathways, the MAP kinase (ERK, JNK, p38) and PI3 kinase/Akt signaling cascades, allow them to impact upon normal and abnormal cell function, thus influencing the cellular processes involved in the initiation and progression of cancer, CVD and neurodegeneration. For example, their ability to activate ERK in neurons leads to a promotion of neuronal survival and cognitive enhancements, both of which influence the progression of Alzheimer's disease, whilst ERK activation by polyphenols in vascular endothelial cells influences nitric oxide production, blood pressure and ultimately CVD risk. The main focus of this review is to provide an overview of the role that polyphenols play in the prevention of cancer, cardiovascular disease and neurodegeneration. We present epidemiological data, human intervention study findings, as well as animal and in vitro studies in support of these actions and in each case we consider how their actions at the cellular level may underpin their physiological effects.
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Nutrients 2010, 2, 1106-1131; doi:10.3390/nu2111106
ISSN 2072-6643
Polyphenols and Human Health: Prevention of Disease and
Mechanisms of Action
David Vauzour, Ana Rodriguez-Mateos, Giulia Corona, Maria Jose Oruna-Concha and
Jeremy P. E. Spencer *
Molecular Nutrition Group, Department of Food and Nutritional Sciences, School of Chemistry,
Food and Pharmacy, The University of Reading, PO Box 226, Reading RG6 6AP, UK;
E-Mails: (D.V.); (A.R.-M.); (G.C.); (M.J.O.-C.)
* Author to whom correspondence should be addressed; E-Mail:;
Tel.: +44-0-118-378-8724; Fax: +44-0-118-931-0080.
Received: 25 September 2010; in revised form: 25 October 2010 / Accepted: 1 November 2010 /
Published: 8 November 2010
Abstract: Polyphenols are found ubiquitously in plants and their regular consumption has
been associated with a reduced risk of a number of chronic diseases, including cancer,
cardiovascular disease (CVD) and neurodegenerative disorders. Rather than exerting direct
antioxidant effects, the mechanisms by which polyphenols express these beneficial
properties appear to involve their interaction with cellular signaling pathways and related
machinery that mediate cell function under both normal and pathological conditions. We
illustrate that their interactions with two such pathways, the MAP kinase (ERK, JNK, p38)
and PI3 kinase/Akt signaling cascades, allow them to impact upon normal and abnormal
cell function, thus influencing the cellular processes involved in the initiation and
progression of cancer, CVD and neurodegeneration. For example, their ability to activate
ERK in neurons leads to a promotion of neuronal survival and cognitive enhancements,
both of which influence the progression of Alzheimers disease, whilst ERK activation by
polyphenols in vascular endothelial cells influences nitric oxide production, blood pressure
and ultimately CVD risk. The main focus of this review is to provide an overview of the
role that polyphenols play in the prevention of cancer, cardiovascular disease and
neurodegeneration. We present epidemiological data, human intervention study findings, as
well as animal and in vitro studies in support of these actions and in each case we consider
how their actions at the cellular level may underpin their physiological effects.
Nutrients 2010, 2
Keywords: polyphenols; cancer; cardiovascular disease; neurodegeneration; advanced
glycation end products; signaling pathways
1. Introduction
Epidemiological studies suggest that high dietary intake of polyphenols is associated with decreased
risk of a range of diseases including cardiovascular disease (CVD), specific forms of cancer [1] and
neurodegenerative diseases [2]. In particular, a group of polyphenols known as flavonoids have been
strongly linked with beneficial effects in many human, animal and in vitro studies [3]. With respect to
cardiovascular health, flavonoids may alter lipid metabolism [4], inhibit low-density lipoprotein (LDL)
oxidation [5], reduce atherosclerotic lesion formation [6] inhibit platelet aggregation [7], decrease
vascular cell adhesion molecule expression [8], improve endothelial function [9] and reduce blood
pressure [10]. However, flavonoids have also been shown to exert beneficial cognitive effects and to
reverse specific age-related neurodegeneration [11] and to exert a variety of anti-carcinogenic effects,
including an ability to induce apoptosis in tumor cells [12-14], inhibit cancer cell proliferation [15,16]
and prevent angiogenesis and tumor cells invasion [17]. This review will detail the evidence for the
role of polyphenols in the context of these three chronic diseases and where relevant, the probable
modes by which they exert their activity in vivo.
2. Polyphenols and Cancer
Cancer refers to a group of diseases that are associated with a disturbance in the control of cell
growth and metabolism [18]. Indeed, the unbalanced control of cellular proliferation is a primary
characteristic of cancer cells and, as such, any molecule capable of inhibiting cancer cell proliferation
may also be useful as a potential chemo-preventive agent [19-22]. There are many different types of
cancer, although breast (predominately women), lung, colorectal and prostate cancer accounts for over
half of all new cases. It is widely believed that a high daily intake of fruit and vegetables helps to
prevent the onset of, and progression of, cancer. Over the past 20 years, case-control studies have
indicated an inverse correlation between regular fruit and vegetable consumption and the development
of various types of cancer [23,24]. More recently, data from large cohort investigations have gone
some way to confirm these epidemiological associations [25-29]. However, there is a degree of
controversy, in that some studies have reported no reduction in bladder, pancreatic and stomach cancer
incidence due to fruit and vegetables intake [30-32] and a recent epidemiological study has provided
evidence for no, or little, association between fruit and vegetable intake and overall cancer risk [25,33].
Despite this, it remains a possibility that specific fruits or vegetables, or specific polyphenols found
within these, may exert protective effects against cancer development, particularly in the
gastrointestinal tract where they will be at highest concentration. In fact, many studies have shown that
various polyphenol-rich fruits and vegetables are particularly effective in protecting against colon
cancer development [34,35].
At the cellular level, there is good evidence that polyphenols present in tea, red wine, cocoa, fruit
juices, and olive oil influence carcinogenesis and tumor development [36]. For example, they may
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interact with reactive intermediates [37] and activated carcinogens and mutagens [38], may modulate
the activity of key proteins involved in controlling cell cycle progression [39] and influence the
expression of many cancer-associated genes [40]. Perhaps most notably, the anticancer properties of
green tea flavanols have been reported in animal models [41], human cell lines [42], as well as in
human intervention studies [43]. Furthermore, green tea consumption has been proposed to
significantly reduce the risk of cancer of the biliary tract [44], bladder [45], breast [46] and colon [47].
Many of the anti-cancer properties associated with green tea are believed to be mediated by the
flavanol, epigallocatechin gallate (EGCG), which has been shown to induce apoptosis and inhibit
cancer cell growth by altering the expression of cell cycle regulatory proteins and the activity of
signaling proteins involved in cell proliferation, transformation and metastasis [48]. In addition to
flavonoids, phenolic alcohols, lignans and secoiridoids (all found at high concentration in olive oil) are
also thought to induce anti-carcinogenic effects [49] and have been reported in large intestinal cancer
cell models [50], in animals [51,52] and in humans [49]. These effects may be mediated by the ability
of olive oil phenolics to inhibit the initiation, promotion and metastasis in human colon
adenocarcinoma cells [53,54] and to down-regulate the expression of COX-2 and Bcl-2 proteins that
have a crucial role in colorectal carcinogenesis [50] (Figure 1).
Polyphenols may exert these anticancer effects via a variety of mechanisms, including removal of
carcinogenic agents [37,49], modulation of cancer cell signaling [48,55] and cell cycle progression
[15,16], promotion of apoptosis [12-14] and modulation of enzymatic activities [56]. For example, the
enhancement of glutathione peroxidase, catalase, NADPH-quinone oxidoreductase, glutathione
S-transferase and/or cytochrome P450 enzyme activity by polyphenols may aid in the detoxification of
carcinogenic agents [57]. Furthermore, they may modulate the activity of signaling pathways [58-60]
(i.e., MAPK kinase and PI3 Kinase), which are involved in cancer cell proliferation [61-63]. The
MAPK signaling pathway has long been viewed as an attractive pathway for anticancer therapies,
based on its central role in regulating the growth and survival of cells from a broad spectrum of human
cancers [64], and its role in the transcriptional and post-transcriptional activation of COX-2 [65]
(Figure 1). In this context, certain polyphenols have been shown to exert a strong inhibitory effect on
the growth of colon adenocarcinoma cells through the inhibition of p38/CREB signaling, a decrease in
COX-2 expression and the stimulation of a G2/M phase cell cycle block [55]. In addition,
hydroxytyrosol [66], epicatechin and dimer B2 [67] have been shown to strongly inhibit ERK1/2
phosphorylation and downstream cyclin D1 expression leading to a block in cell cycle progression
(Figure 1). Alternatively, polyphenols such as hydroxytyrosol and tea flavanols such as EGCG have
been shown to reduce COX-2 over-expression, which is associated with colorectal neoplasia in
colorectal cancer [68-71].
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Figure 1. The interaction of polyphenols with cellular signaling pathways involved in
chronic disease. Flavonoid-induced activation and/or inhibition of MAP kinase and PI3
kinase signaling leads to the activation of transcription factors which drive gene
expression. For example, activation of ERK/Akt and the downstream transcription factor
CREB by flavonoids may promote changes in neuronal viability and synaptic plasticity,
which ultimately influence neurodegenerative processes. Polyphenol-induced inhibition of
the JNK, ASK1 and p38 pathways leads to inhibition of both apoptosis in neurons and a
reduction of neuroinflammatory reactions in microglia (reduced iNOS expression and NO
release). Alternatively, their interaction with signaling may lead to direct activation of
proteins such as eNOS, which controls nitric oxide release in the vasculature and thus
influences CVD risk.
Tumors are also characterized by an increase in glucose uptake and a high rate of glycolysis, which
can led to the non-enzymatic glycation of proteins and the generation of so called advanced glycation
end products (AGEs). Indeed, the measurement of the AGEs, NЄ-carboxymethyllysine (CML) and
argpyrimidine in several human tumors has been linked to their involvement in cancer progression
[72]. Certain polyphenols have been proposed to counteract AGE formation both in vivo and in vitro
and thus may limit their impact on the carcinogenesis process [73-76]. Furthermore, receptors for
AGEs, such as RAGE, have also been recognized to play an important role in regulating cancer cell
invasion and metastasis [77,78] (Figure 2) and flavanols such as EGCG may inhibit the cancer cell
proliferation by blocking RAGE related signaling [79].
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Figure 2. Formation of Advanced Glycation Endproducts (AGEs) and the sites where
flavonoids may inhibit their formation (*). These include monosaccharide autoxidation,
glycation, glycoxidation, as well as AGE receptor binding, which results in the activation
and release of inflammation mediators.
3. Polyphenols and Cardiovascular Disease
Cardiovascular disease (CVD), in particular coronary heart disease and stroke, is a major cause of
mortality in developed nations [80]. CVD is a chronic, multi-factorial disease in which a range of
genetic and environmental factors plays a role in its initiation, progression and development. For
example, smoking, high saturated fat diets and physical inactivity are well known environmental
factors that are known to increase the risk of CVD [81-84]. This array and variety of factors makes it
difficult to explore the impact that an individual factor, for example a specific dietary nutrient, has on
the progression of CVD. Despite this, numerous epidemiological and human intervention studies have
suggested that regular consumption of polyphenol-rich foods, such as fruits, vegetables, cocoa, tea and
wine, may exert cardio-protective effects in humans [85-94]. Prospective studies have indicated a
correlation between the intake of flavonols, flavones and flavanols and a reduced risk of coronary
artery disease [95] and anthocyanin and flavanone intake and reduced CVD related mortality [90].
Furthermore, meta-analyses have indicated that the consumption of three cups of tea per day reduces
CVD risk by 11% [96] and regular, moderate red wine consumption is associated with a 32% reduced
Nutrients 2010, 2
risk of CVD [97]. However, there remains significant debate over which polyphenols are active, or
most active, in the context of CVD. Indeed, a recent systematic review has concluded that soy and
cocoa flavonoids have the most beneficial effect on reducing cardiovascular risk [98], whilst other
polyphenols are ineffective [87,99-101]. The reasons for these inconsistencies may relate to a number
of factors, including the use of different dietary intake questionnaires and food composition tables,
differences in the levels and types of polyphenols studied and differences in the populations
investigated, such as well-nourished populations and populations with high polyphenol intake showing
no effect [102].
Various human, animal and cell studies have suggested that polyphenols may exert beneficial
effects on the vascular system via an induction of antioxidant defenses [103-105], by lowering blood
pressure [98,106-111], by improving endothelial function [108,112-121], by inhibiting platelet
aggregation [107,122-124] and low density lipoprotein oxidation [105,125] and by reducing
inflammatory responses [126,127]. A daily intake of flavanol containing cocoa was found to be the
causal factor in determining the relatively low incidence of hypertension and CVD incidence in the
Kuna Amerinds of the San Blas Island in Panama [128]. In support of these findings, three recent
meta-analyses have confirmed the blood pressure lowering capacity of flavanol-rich cocoa
[98,106,110]. Whilst a correlation between high black tea consumption and decreased blood pressure
has been reported [129,130], the effects of tea polyphenols have proved less consistent, with reports
indicating they both reduce blood pressure [131] or have no effect in animal models [132].
Furthermore, unlike those studies with cocoa, human intervention studies investigating the short-term
effect of tea consumption on blood pressure have failed to show positive effects [133-136] and there are
inconsistent data with regards to the effect of red wine or grapes on blood pressure [88,89,111,137-140].
However, in general there is a growing body of evidence to support the short-term and long-term
benefits of cocoa, purple grape juice, tea and red wine consumption with regards to endothelial
function and CVD risk [104,108,112-115,133,135,141-145].
One suggested mechanism for the action of polyphenols on vascular function involves their ability
to modulate the levels of and activity of nitric oxide synthase (eNOS) and therefore nitric oxide (NO)
bioavailability to the endothelium [112,146-150] (Figure 1). In support of this, aortic ring experiments
using physiological concentrations of polyphenols have shown that polyphenols induce
endothelium-dependent relaxation [148,151-156]. This regulation of vascular nitric oxide is thought to
involve the ability of polyphenols to interact with kinase signaling pathways such as the
PI3-kinase/Akt pathway and intracellular Ca+2 on eNOS phosphorylation and subsequent NO
production [157,158] (Figure 1). As well as activating eNOS, many polyphenols have also been shown
to increase eNOS expression, to induce prostacyclin production, to inhibit endothelin-1 and endothelial
NADPH oxidase [149,159-162] and to inhibit angiogenesis and the migration and proliferation of
vascular cells and matrix metalloproteinase (MMP) activation [158]. They have also been proposed to
inhibit platelet aggregation [163,164] with cocoa, purple grape juice, red wine, black tea, coffee and
berry interventions all effective in acutely and chronically inhibiting platelet activation and
aggregation [107,122,123,164-169]. Lastly, flavanols and flavonols may act to prevent AGE-related
vascular injury [170,171] via their regulation of MAPK signaling through RAGE [172] and the
down-regulation of transcription factors such as NF-kB leading to the suppression of NADPH
oxidase [173] (Figure 1).
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4. Polyphenols and Neurodegeneration
Neurodegenerative disorders such as Parkinsons and Alzheimers diseases represent an increasing
problem in our aging societies, primarily as there is an increased prevalence of both Alzheimers
disease [174,175] and Parkinsons disease [175-177] with age. These and other neurodegenerative
disorders appear to be triggered by multi-factorial events including neuroinflammation, glutamatergic
excitotoxicity, increases in oxidative stress, iron and/or depletion of endogenous antioxidants [178-180].
In terms of dietary modulation of these diseases, epidemiological studies have suggested that moderate
wine consumption may reduce the incidence of certain age-related neurological disorders including
Alzheimers disease [181-183]. Furthermore, regular dietary intake of flavonoid-rich foods and/or
beverages has been associated with 50% reduction in the risk of dementia [184], a preservation of
cognitive performance with ageing [185,186], a delay in the onset of Alzheimers disease [187] and a
reduction in the risk of developing Parkinsons disease [2].
Many studies have reported the bioavailability of polyphenols in the systemic circulation [188-191].
Whilst less is known regarding their degree of brain bioavailability, flavanones such as hesperetin,
naringenin and their in vivo metabolites, have been shown to traverse the BBB in relevant in vitro and
in situ models [192]. Moreover, several anthocyanins have also been identified in the cortex and
cerebellum of rat [193] and pig [194,195] following feeding with blueberries. Together, these results
suggest that polyphenols are able to transverse the BBB, albeit to varying degrees depending on their
structure. Thus, such compounds are likely to be candidates for direct neuroprotective and
neuromodulatory actions.
Flavonoids may act to protect the brain in a number of ways, including by protection of vulnerable
neurons, the enhancement of existing neuronal function or by stimulating neuronal regeneration [196].
For example, polyphenols have been shown to protect neurons against oxidative stress [197] and
-induced-induced neuronal injury [198] and polyphenol-rich Ginkgo biloba extracts have been
shown to be neuroprotective [199] by protecting hippocampal neurons from nitric oxide- and
beta-amyloid-induced neurotoxicity [200]. Furthermore, anthocyanins and isoflavones [201,202] may
be capable of reducing the neurodegeneration associated with the accumulation AGEs during normal
[203] and abnormal brain ageing [204]. In the context of Parkinsons disease, the citrus flavanone
tangeretin has been observed to maintain nigro-striatal integrity and functionality following lesioning
with 6-hydroxydopamine, suggesting that it may serve as a potential neuroprotective agent against the
underlying pathology associated with Parkinsons disease [205]. In addition to the neuroprotection
elicited by flavonoids, phenolic compounds such as caffeic acid and tyrosol has also been shown to
protect against 5-S-cysteinyl-dopamine [206] and peroxynitrite neurotoxicity [207] in vitro.
There is also a growing interest in the potential of polyphenols to improve memory, learning and
general cognitive ability [208-211]. Human investigations have suggested that fruits and vegetables
may have an impact on memory [212-214] and depression [215] and there is a large body of animal
behavioral evidence to suggest that berries, in particular blueberries and strawberries, are effective at
reversing age-related deficits in spatial working memory [216-221], in improving object recognition
memory [222] and in modulating inhibitory fear conditioning [220,221]. The beneficial effects of
flavonoid-rich foods and beverages on psychomotor activity in older animals have also been reported
[217,223]. In addition to berries, tea [35,224], pomegranate [225], Ginkgo biloba [226-235] and pure
Nutrients 2010, 2
flavonols such as quercetin, rutin [236] and fisetin [237] have also been shown to be beneficial in
reversing neuronal and behavioral aging. Furthermore, Ginkgo biloba has been shown to promote
inhibitory avoidance conditioning in rats with high-dose intake leading to short-term, but not
long-term, passive avoidance learning in senescent mice [238,239].
The effects of polyphenols on cognition and against neurodegenerative processes appear to be
mediated via their interactions with neuronal and glial signaling pathways that affect gene expression
and interfere with the cell death mechanisms [233,234]. For example, flavonoids may exert direct
modulation of protein and lipid kinase signaling pathways [209,232,234], via the inhibition of MAPK
signaling cascades, such as p38 or ERK1/2 [226,240] (Figure 1). The effects of flavonoids on these
kinases may influence downstream transcription factors [240], including nuclear factor-Kappa B
(NF-κB) [202,241], which responds to p38 signaling and is involved in iNOS induction [242]. This
suggests that there may be interplay between signaling pathways, transcription factors and cytokine
production in determining the neuroinflammatory response in the CNS (Figure 1). In addition, the
actions of flavonoids on neuronal signaling may mediate their ability to protect against neurotoxicity
induced by AGEs [243].
5. Summary
Polyphenols are found ubiquitously in plants and are therefore consumed in relatively high
quantities in the human diet. Over the last 20 years, a significant amount of data has emerged with
regards to the potential health effects of several classes of polyphenolic compounds, in particular
flavonoids. Along with this, reasonable understandings of the bioavailability of polyphenols and the
mechanisms by which they exert such benefits in vivo have been determined. These mechanisms are
now believed to involve interactions with a number of cellular signaling pathways, which are
important in the normal functioning of cells. Such interactions appear to modulate these pathways in a
way that acts to control various pathogenic processes relevant to chronic disease progression. In this
respect, polyphenols, in particular flavonoids structurally resemble inhibitors of cell signaling
cascades, such as the PD98059, a MAPK inhibitor and the LY294002, a phosphatidylinositol-3 kinase
(PI3) inhibitor. Indeed, the latter inhibitor was modeled on the structure of quercetin [244]. LY294002
and quercetin fit into the ATP binding pocket of the enzyme and it appears that the number and
substitution of hydroxyl groups on the B ring and the degree of un-saturation of the C2-C3 bond are
important determinants of this particular bioactivity. In this regard, quercetin and some of its in vivo
metabolites have been suggested to inhibit Akt/protein kinase B (PKB) signaling pathways [245], a
mechanism of action consistent with quercetin and its metabolites acting at and inhibiting PI3-kinase
activity. Although we have gained a better understanding of how polyphenols interact with cells, there
is still a long way to go before the precise cellular targets and mechanisms of action can be established.
While various lines of evidence via biomarker assessments and the use of pharmacological tools
in vivo (i.e., specific enzyme inhibitors, receptor agonists or antagonist) have indicated several
potential mechanisms of action, a comprehensive proof and conclusive understanding has yet to be
established. This relates mainly to significant limitations with regard to current data from in vitro
investigations that aimed at elucidating the mechanisms of action by which polyphenols exert their
bioactivities in vivo. It is notable that in most cases, in vitro data with regards to polyphenol bioactivity
Nutrients 2010, 2
have been derived via the direct use of plant/food extracts or isolated native compounds, a practice that
does not take into account the processes of absorption and metabolism that polyphenols undergo in
humans. As such, one should express caution when interpreting the wealth of in vitro data linking
numerous polyphenols to actions in the body and effects against various disease processes, especially
if no data has been collected regarding the action of physiological metabolites of polyphenols in the
same cell systems. For example, if there is no evidence for the absorption of a particular polyphenol in
humans, can one really gain meaningful insight into its biological effects by exposing it to cultured
cells of the cardiovascular system and/or brain? There are specific exceptions, for example the
gastrointestinal tract, where polyphenols may come into direct contact with the cells without having
undergone absorption and metabolism. Therefore, it is perhaps relevant to investigate the effects of
polyphenols and polyphenol extracts on colon cancer cells, although as the gut microbiota also
extensively metabolizes them one must take account of these effects prior to concluding on a
mechanism of action in vivo. These and other limitations significantly hamper the translation of
in vitro data on the biological effects of flavanols and procyanidins into meaningful insight and
mechanistic understanding of the in vivo effects in humans.
Whilst the case for the biological functions of polyphenols in humans is accumulating, there
remains insufficient evidence to claim clear and undisputed positive health effects relating to their
consumption, particularly with regards to long-term dietary ingestion and human health.
Epidemiological studies have failed to show conclusive results, in some cases due to the lack of
appropriate nutrient databases and/or the use of an inappropriately controlled study population. Much
of the strongest data, particularly with regards to CVD, is based on short-term human studies, in many
cases lacking appropriate controls and a defined polyphenol content of the foods assessed. In addition
to better-defined human intervention studies aimed at assessing physiological endpoints linked to
disease, further research is also required regarding the bioavailability of polyphenols, particularly with
regards to the effects of food matrices on absorption and the influence on age, gender and genotype on
both absorption and metabolism These studies are required in order to help determine the physiological
metabolic forms responsible for activity in vivo, as well as to help define adequate biomarkers of
polyphenol intake. Therefore, at present, while the vast literature regarding the potential of
polyphenols to improve in human health is encouraging, more long-term, randomized, controlled,
dietary intervention trials with appropriate controls are warranted in order to assess the full and
unequivocal role that polyphenols play in preventing chronic human disease. The outcomes of these
studies may ultimately be used to make specific dietary recommendations regarding the efficacy of
polyphenols in preventing chronic disease risk and to fully validate polyphenols as the new agents
against various chronic human diseases.
The authors are funded by the Biotechnology and Biological Sciences Research Council
(BB/F008953/1; BB/E023185/1; BB/G005702/1), the FSA (FLAVURS) and the European Union
(FP7 FLAVIOLA). There is no conflict of interest to disclose, having read the Journals guidelines. All
authors contributed to the preparation of the manuscript and agreed the final version.
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© 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
... Phenolic compounds have attracted significant interest in the food industry because their potential health benefits. (Vauzour et al. 2010) Among these phenolic compounds, hydroquinone (HQ) and catechol (CC) are widely used as antioxidant, cosmetics and pesticides. (Zaric et al. 2004;Nguyen et al. 2019) Besides their applications, HQ and CC also identified as serious pollutants in the ecological environment due to their slow degradation and toxicity in animals and plants (Topping et al. 2007;Hasanpour et al. 2019). ...
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Natural graphite has a large electrical conductivity in plane direction, hundreds times of that in vertical direction. Regulating graphite flakes perpendicular to the plane will improve the performance of the sensor. As a non-connected method, magnetic field-assisted orientation can be no-additives. However, some studies believe that diamagnetic materials are non-magnetic, and must be doped by ferromagnetic materials before oriented by a magnetic field. Here, original graphite flakes were vertically oriented by a low magnetic field during the electrode preparation to increase effective surface area. The performance of electrode was enhanced in both potassium ferricyanide/potassium ferrocyanide probe system and detection of hydroqui-none (HQ) and catechol (CC). For HQ and CC detection, the sensitivities of vertically oriented graphite flakes electrode are 5.05 times and 6.35 times higher than that of graphite flakes without magnetic field, respectively. This magnetic alignment technology could construct other electrode materials for electrochemical sensors.
... Plant polyphenols are a diverse group of phytomolecules that are considered important constituents of a healthy diet due to their well-documented role in modulating human health. Polyphenols have been reported to confer cytoprotective and health beneficial effects through the modulation of several cell signaling pathways such as NRF2, NF-κB, mTOR, Sirtuins as well as key processes such as autophagy, immunomodulation, cell proliferation, and apoptosis (Cory et al., 2018;Vauzour et al., 2010). In addition, studies suggest that long term consumption of dietary polyphenols confers a protective role in abating a multitude of age-related degenerative diseases like cancer (Lee and Lee, 2006), cardiovascular diseases (Khurana et al., 2013), muscular atrophy (Nikawa et al., 2021), neurodegenerative diseases (Rossi et al., 2008), arthritis (Behl et al., 2021), and even organismal longevity (Queen and Tollefsbol, 2010). ...
The process of cellular senescence is rapidly emerging as a modulator of organismal aging and disease. Targeting the development and removal of senescent cells is considered a viable approach to achieving improved organismal healthspan and lifespan. Nutrition and health are intimately linked and an appropriate dietary regimen can greatly impact organismal response to stress and diseases including during aging. With a renewed focus on cellular senescence, emerging studies demonstrate that both primary and secondary nutritional elements such as carbohydrates, proteins, fatty acids, vitamins, minerals, polyphenols, and probiotics can influence multiple aspects of cellular senescence. The present review describes the recent molecular aspects of cellular senescence-mediated understanding of aging and then studies available evidence of the cellular senescence modulatory attributes of major and minor dietary elements. Underlying pathways and future research directions are deliberated to promote a nutrition-centric approach for targeting cellular senescence and thus improving human health and longevity.
... Type-2 diabetes results in beta cell death due to a variety of mechanisms, including increased glucotoxicity, lipotoxicity, stress on the endoplasmic reticulum, and apoptosis (Ndisang et al., 2017). Hyperglycemia, a long-term rise in blood sugar levels, is linked to an increased risk of developing type 2 diabetes in those who consume large amounts of carbohydrates (Vauzour et al., 2010). The glycemic index (GI) is a physiological measure of how carbohydrates in diet cause a rise in postprandial blood glucose levels. ...
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Plants produce polyphenols, which are considered highly essential functional foods in our diet. They are classified into several groups according to their diverse chemical structures. Flavanoids, lignans, stilbenes, and phenolic acids are the four main families of polyphenols. Several in vivo and in vitro research have been conducted so far to evaluate their health consequences. Polyphenols serve a vital function in the protection of the organism from external stimuli and in eliminating reactive oxygen species (ROS), which are instigators of several illnesses. Polyphenols are present in tea, chocolate, fruits, and vegetables with the potential to positively influence human health. For instance, cocoa flavan‐3‐ols have been associated with a decreased risk of myocardial infarction, stroke, and diabetes. Polyphenols in the diet also help to improve lipid profiles, blood pressure, insulin resistance, and systemic inflammation. Quercetin, a flavonoid, and resveratrol, a stilbene, have been linked to improved cardiovascular health. Dietary polyphenols potential to elicit therapeutic effects might be attributed, at least in part, to a bidirectional association with the gut microbiome. This is because polyphenols are known to affect the gut microbiome composition in ways that lead to better human health. Specifically, the gut microbiome converts polyphenols into bioactive compounds that have therapeutic effects. In this review, the antioxidant, cytotoxicity, anti‐inflammatory, antihypertensive, and anti‐diabetic actions of polyphenols are described based on findings from in vivo and in vitro experimental trials. Practical applications The non‐communicable diseases (NCDs) burden has been increasing worldwide due to the sedentary lifestyle and several other factors such as smoking, junk food, etc. Scientific literature evidence supports the use of plant‐based food polyphenols as therapeutic agents that could help to alleviate NCD's burden. Thus, consuming polyphenolic compounds from natural sources could be an effective solution to mitigate NCDs concerns. It is also discussed how natural antioxidants from medicinal plants might help prevent or repair damage caused by free radicals, such as oxidative stress.
... The favorable effects of polyphenols are attributed mainly to their antioxidant capacity and ability to modulate the cellular antioxidant defense mechanisms by inducing synthesis of detoxication enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), NAD(P)H: quinone oxidoreductase 1 (NQO1), side by side with others [35,36]. Apart from that, recent studies have provided evidence of the effect of polyphenols as modulators of signaling pathways, such as TNFα, IL-12p40 (a component of the cytokines interleukin IL-12 and IL-23), and p38 MAPK (a class of mitogen-activated protein kinases) [37,38]. ...
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The aim of the study is to evaluate the effect of Aronia melanocarpa fruit juice (AMJ) supplementation on age-related coronary arteries remodeled in aged rat hearts. Male Wistar rats (n = 24) were divided into three groups: (1) young controls (CY), aged 2 months, without AMJ supplementation; (2) old controls (CO), aged 27 months, without AMJ supplementation; and (3) the AMJ group (A), which used 27-month old animals, supplemented orally with AMJ for 105 days. AMJ supplementation did not influence the wall-to-diameter parameter (Kernohan index) of the coronary arteries of test animals. Aged rats supplemented with AMJ showed a significant decrease in the amount of collagen fibers in their coronary tunica media, as compared with the old controls. The intensity of the immunoreaction for alpha smooth muscle actin (αSMA) in the coronary tunica media was significantly lower in the supplemented group than in the old controls. The intensity of the angiotensin-converting enzyme 2 (ACE2) immunoreaction in the coronary tunica media of the supplemented group was significantly higher than the one observed in the old controls. These results indicate the positive effects of AMJ supplementation on the age-dependent remodeling of coronary arteries and support for the preventive potential of antioxidant-rich functional food supplementation in age-related diseases.
... Calorie consumption, caffeine, alcohol, and metals absorbed through food and lipids, among other factors, have been linked to Alzheimer's related parameters such as epigenetic, β-amyloid, tau proteins, oxidative stress, and oxygen reactive species (ROS) (Fernández-Sanz et al., 2019). Several in-vitro, in-vivo, and human epidemiological investigations have demonstrated a range of dietary components that influence the incidence of Parkinson's and Alzheimer's disease Vauzour et al., 2010). Gao et al. (2007) investigated relationships between dietary habits and the risk of Parkinson's disease in the health professional's follow-up study (1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) and the nurse's health study (1984)(1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000). ...
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Neurodegeneration leads to the loss of structural and functioning components of neurons over time. Various studies have related neurodegeneration to a number of degenerative disorders. Neurological repercussions of neurodegeneration can have severe impacts on the physical and mental health of patients. In the recent past, various neurodegenerative ailments such as Alzheimer’s and Parkinson’s illnesses have received global consideration owing to their global occurrence. Environmental attributes have been regarded as the main contributors to neural dysfunction-related disorders. The majority of neurological diseases are mainly related to prenatal and postnatal exposure to industrially produced environmental toxins. Some neurotoxic metals, like lead (Pb), aluminium (Al), Mercury (Hg), manganese (Mn), cadmium (Cd), and arsenic (As), and also pesticides and metal-based nanoparticles, have been implicated in Parkinson’s and Alzheimer’s disease. The contaminants are known for their ability to produce senile or amyloid plaques and neurofibrillary tangles (NFTs), which are the key features of these neurological dysfunctions. Besides, solvent exposure is also a significant contributor to neurological diseases. This study recapitulates the role of environmental neurotoxins on neurodegeneration with special emphasis on major neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.
... In addition, they also contain relatively high amounts of mangiferin, gallotannins, and phenolic acids (Masibo and He 2008), which are non-essential nutrients that have, however, been demonstrated to exert beneficial impacts on health (Burton-Freeman et al. 2017). For instance, these dietary phenolic compounds have been described to be potent modulators of several regulatory pathways for lipid and glucose metabolism as well as antioxidant and inflammatory processes (Scalbert et al. 2005;Vauzour et al. 2010;Rios-Hoyo et al. 2014). Moreover, they have been touted as having strong anti-cancer potential, including anti-breast cancer (Mirza et al. 2021;Yap et al. 2021). ...
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This study aimed to explore the impact of daily mango consumption (Mangifera indica) on cardiometabolic health and gut microbiota in individuals with overweight and obesity. Changes in cardiometabolic variables, gut microbiota diversity and composition, physical activity habits, and dietary intakes were assessed in 8 males and 19 females with overweight and obesity who consumed 280 g/day of mango pulp for 8 weeks. There were no significant changes in body weight, waist circumference, or plasma lipid levels. However, after consuming mangos for 8 weeks, participants showed a 3.5% reduction in systolic blood pressure (–4 ± 6 mm Hg, p = 0.011) as well as a 10.5% reduction in 2-hour plasma glucose concentration after a 75-g oral glucose tolerance test (–0.58 ± 1.03 mmol/L, p = 0.008). These beneficial cardiometabolic outcomes were accompanied with enhanced gut microbiota diversity and with changes in the abundance of specific gut bacterial species. Mango consumption may have beneficial effects on both blood pressure and glucose homeostasis in individuals with overweight and obesity. Further studies are warranted to determine the impact of long-term and regular mango intake on cardiometabolic risk factors of individuals with overweight and obesity, and the potential mechanisms linking gut microbial changes to those health benefits. This study was registered with as NCT03825276. Novelty: A 3.5% reduction in systolic blood pressure is noted after consuming mangos for 8 weeks. A 10.5% reduction in 2-hour plasma glucose concentration of an oral glucose tolerance test is observed after consuming mangos for 8 weeks. Mango consumption for 8 weeks may enhance gut microbial diversity and abundance of specific bacterial species.
... Phenolic compounds are one of the main classes of natural molecules with therapeutic properties. Most of their beneficial effects can be ascribed to their antioxidant properties as scavengers of free radicals generated from various sources in the environment, as well as from cellular processes [4], thus preventing human diseases associated with oxidative cell stress, such as diabetes, obesity, and atherosclerosis [5,6]. Furthermore, several studies have clearly demonstrated that dietary polyphenols are among the naturally occurring substances that have shown promising anticancer properties [7,8]. ...
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In the current study, we determined the antioxidant properties of “Greco” grape cane extracts, a typical cultivar of southern Italy. We also explored the anticancer activity of the polyphenol-rich fraction of the extract on head and neck squamous carcinoma cells (HNSCC) and investigated the underlying mechanism. Aqueous extracts were prepared at different pHs and extraction times and the total phenolic and reducing sugar contents were estimated. Radical Scavenging Activity (RSA), Ferric Reducing Antioxidant Power (FRAP), and Total Antioxidant Capacity (TAC) of the extracts were measured. A polyphenol-rich fraction, accounting for 6.7% by weight and characterized mainly by procyanidins and stilbenoids, was prepared from the extract obtained at pH 7 for 60 min. We demonstrated that the extract exerted a cytotoxic effect on HNSCC cell lines by inducing cell cycle arrest via cyclin downregulation and p21 upregulation, and by triggering apoptosis through caspase cascade activation, PARP-1 cleavage, and an increase in the Bax/Bcl-2 ratio. We furnished evidence that the polyphenol-rich fraction played the major role in the anticancer activity of the extract. These outcomes highlighted grape canes from the “Greco” cultivar as a valuable source of polyphenols that may represent good candidates for the design of innovative adjuvant therapies in the treatment of HNSCC.
... Previous studies have shown that plant extracts and polyphenolic compounds may have a beneficial role in several diseases including cancer [22][23][24][25][26] . Mechanisms related to the regulation of immune system, inactivation of arachidonic acids pathways, inactivation of NF-κB (nuclear factor kappalight-chain-enhancer of activated B cells), suppression of toll-like receptor and antioxi-dant activity 27 may be involved. ...
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The treatment of cancer patients with anti-cancer drugs is often accompanied by the presence of undesirable side effects. The use of natural plant derivatives alone, or in conjunction with existing anti-neoplastic drugs, has been suggested to obtain better results and decrease these side effects. Nitric oxide (NO•), the hypoxia-inducible factor-1 (HIF-1), and decreased concentration of actin play important roles in cancer progression. The beneficial effects of polyphenols in various organ disorders including cancer has been reported. The aim of this study was to determine the effect of Arracacia xanthorrhiza Bancr extracts, white (WAXB) and red (RAXB) variants (compounds rich in polyphenols) on the concentrations of β-actin, NO• and HIF-1 in Hela cells cultures, to uncover possible anti-neoplastic effects. Extracts from the plant leaves were added to Hela cell cultures at a concentration of 10-3 mg/mL, and after 24 hours of culture, the concentrations of β-actin, NO• and HIF-1 were determined by immunohistochemical, biochemical and western blot assays. Both extracts reduced the concentrations of β-actin, NO• and HIF-1 (p<0.001), similar to the methotrexate effect. These results suggest an antineoplastic effect of the studied plant extracts and highlight the possibility of their use in the treatment of neoplasms.
... Plant flavonoids have been illustrated to be antioxidants and anti-inflammatory against cerebral ischemia injury . They also have antiradical properties to prevent the associated diseases (Rice-Evans et al., 1996;Pan F. et al., 2017) by activating related gene expression, by interacting with MAP-kinase and PI3-kinase, and having an enzyme activity that can mediate cellular signaling transduction and other pathways (Seifried et al., 2007;Vauzour et al., 2010). Flavonoids were one of the main active metabolites in the JHK, and the accumulation of flavonoids in the flower can be up to 5.6% of the dry weight (Yang, 2013), which is ten times higher than that of ginkgo biloba and soybean (commonly used in industry to extract flavonoids) (Zhou et al., 2021). ...
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Hibiseu manihot L. (Jinhuakui, JHK), also known as a garden landscape plant, is widely cultivated as a landscape plant having pharmacological effects due to its high flavonoids content. Although flavonoids were the main active pharmaceutical ingredients in JHK, little information was obtained about the content, composition, and accumulation pattern of flavonoids in different tissues. Most studies only identified a few kinds of flavonoids in JHK limited by separation and identification problems. Therefore, combined metabolome and transcriptome analysis was performed to explore the accumulation patterns and biosynthesis mechanisms of flavonoids in JHK. In this study, we identified 160 flavonoids in 15 samples of JHK (flower, leaf, root, stem, and seeds) by using LC-MS/MS. Consistent with the total flavonoid content determination, these flavonoids were significantly accumulated in flowers, followed by leaves, stems, roots, and seeds. Among them, certain flavonoids, with high content, were also identified for the first time in JHK, such as tricetin, catechin, hesperidin, ncyanidin-3-O-sambubioside, astragalin, procyanidin B2/B3/C1, apigenin-5-O-glucoside, etc. Different tissues underwent significantly reprogramming of their transcriptomes and metabolites changes in JHK, particularly in the flavonoid, flavone, and flavonol biosynthesis pathways. We conducted a correlation analysis between RNA-seq and LC-MS/MS to identify the key genes and related flavonoids compounds, rebuild the gene-metabolites regulatory subnetworks, and then identified 15 key genes highly related to flavonoids accumulation in JHK. These key genes might play a fine regulatory role in flavonoids biosynthesis by affecting the gene expression level in different organs of JHK. Our results could be helpful for the improvement of the market/industrial utilization value of different parts of JHK, to pave the way for the regulatory mechanism research of flavonoids biosynthesis, and provide insight for studying the production quality improvement of JHK.
This review is intended to cover the works related to the anthocyanin behavior in food that is subjected to drying. Both experimental and theoretical results available in scientific literature are discussed. An increase in anthocyanin concentration has been observed upon thermal processing. Nevertheless, a conclusive explanation is still unavailable. The accessible studies suggest an increase in concentration during maturations, which could be related to the enzymatic activity. The possible enzymes involved in such a procedure have also been covered, including their role played in the process. The possible activation mechanisms and the related factors such as temperature, pH, oxygen contents and the presence of UV-light irradiation were also considered. Moreover, the metabolic pathways were also explored including experimental evaluation and theoretical models based on atomistic methodologies such as density functional theory (DFT). This review is aimed to provide a comprehensive overview of the probable mechanisms behind the increase of anthocyanin concentration during drying.
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For some classes of dietary polyphenols, there are now sufficient intervention studies to indicate the type and magnitude of effects among humans in vivo, on the basis of short-term changes in biomarkers. Isoflavones (genistein and daidzein, found in soy) have significant effects on bone health among postmenopausal women, together with some weak hormonal effects. Monomeric catechins (found at especially high concentrations in tea) have effects on plasma antioxidant biomarkers and energy metabolism. Procyanidins (oligomeric catechins found at high concentrations in red wine, grapes, cocoa, cranberries, apples, and some supplements such as Pycnogenol) have pronounced effects on the vascular system, including but not limited to plasma antioxidant activity. Quercetin (the main representative of the flavonol class, found at high concentrations in onions, apples, red wine, broccoli, tea, and Ginkgo biloba) influences some carcinogenesis markers and has small effects on plasma antioxidant biomarkers in vivo, although some studies failed to find this effect. Compared with the effects of polyphenols in vitro, the effects in vivo, although significant, are more limited. The reasons for this are 1) lack of validated in vivo biomarkers, especially in the area of carcinogenesis; 2) lack of long-term studies; and 3) lack of understanding or consideration of bioavailability in the in vitro studies, which are subsequently used for the design of in vivo experiments. It is time to rethink the design of in vitro and in vivo studies, so that these issues are carefully considered. The length of human intervention studies should be increased, to more closely reflect the long-term dietary consumption of polyphenols.
Apigenin, a common dietary flavonoid, has been shown to induce cell cycle arrest in both epidermal and fibroblast cells and inhibit skin tumorigenesis in murine models. The present study assessed the influence of apigenin on cell growth and the cell cycle in the human colon carcinoma cell lines SW480, HT‐29, and Caco‐2. Treatment of each cell line with apigenin (0–80 μM) resulted in a dose‐dependent reduction in both cell number and cellular protein content, compared with untreated control cultures. DNA flow cytometric analysis indicated that treatment with apigenin resulted in G2/M arrest in all three cell lines in a time‐ and dose‐dependent manner. Apigenin treatment (80 μM) for 48 h produced maximum G2/M arrest of 64%, 42%, and 26% in SW480 cells, HT‐29 cells, and Caco‐2 cells, respectively, in comparison with control cells (15%). The proportion of S‐phase cells was not altered by apigenin treatment in each of the three cell lines. The G2/M arrest was reversible after 48 h of apigenin treatment in the most sensitive cell line SW480. The degree of G2/M arrest by apigenin was inversely correlated with the corresponding inhibition of cell growth measurements in all three cell lines (r = −0.626 to −0.917, P≤0.005). Moreover, an immune complex kinase assay demonstrated an inhibition of p34cdc2 kinase activity, a critical enzyme in G2/M transition, in each cell line after treatment with apigenin (50–80 μM). Western blot analyses indicated that both p34cdc2 and cyclin B1 proteins were also decreased after apigenin treatment. These results indicate that apigenin inhibits colon carcinoma cell growth by inducing a reversible G2/M arrest and that this arrest is associated, at least in part, with inhibited activity of p34cdc2 kinase and reduced accumulation of p34cdc2 and cyclin B1 proteins. Differences in induction of G2/M arrest by apigenin in the three colon carcinoma cell lines suggest that dietary apigenin may be differentially effective against tumors with specific mutational spectra. Mol. Carcinog. 28:102–110, 2000. © 2000 Wiley‐Liss, Inc.
The aim of this study was to examine the effects of procyanidins derived from cocoa on vascular smooth muscle. Two hypotheses were tested: 1) extracts of cocoa, which are rich in procyanidins, cause endothelium-dependent relaxation (EDR), and 2) extracts of cocoa activate endothelial nitric oxide synthase (NOS), The experiments were carried out on aortic rings obtained from New Zealand White rabbits. The polymeric procyanidins (tetramer through decamer of catechin) caused an EDR. In addition, the Ca2+-dependent NOS activity, measured by the L-arginine to L-citrulline conversion assay, was significantly increased in aortic endothelial cells exposed to polymeric procyanidins, whereas monomeric compounds had no such effect. These findings demonstrate that polymeric procyanidins cause an EDR that is mediated by activation of NOS.
Phosphatidylinositol (PtdIns) 3-kinase is an enzyme implicated in growth factor signal transduction by associating with receptor and nonreceptor tyrosine kinases, including the platelet-derived growth factor receptor. Inhibitors of PtdIns 3-kinase could potentially give a better understanding of the function and regulatory mechanisms of the enzyme. Quercetin, a naturally occurring bioflavinoid, was previously shown to inhibit PtdIns 3-kinase with an IC50 of 1.3 mu/ml (3.8 mu M); inhibition appeared to be directed at the ATP-binding site of the kinase. Analogs of quercetin were investigated as PtdIns 3-kinase inhibitors, with the most potent ones exhibiting IC50, values in the range of 1.7-8.4 mu g/mI. In contrast, genistein, a potent tyrosine kinase inhibitor of the isoflavone class, did not inhibit PtdIns 3-kinase significantly (IC50 > 30 mu g/ml). Since quercetin has also been shown to inhibit other PtdIns and protein kinases, other chromones were evaluated as inhibitors of PtdIns 3-kinase without affecting PtdIns 4-kinase or selected protein kinases. One such compound, 2-(4-morpholinyl)8-phenyl-4H-1-benzopyran-4-one (also known as 2-(4-morpholinyl-8-phenylchromone, LY294002), completely and specifically abolished PtdIns 3-kinase activity (IC50 = 0.43 mu g/ml; 1.40 mu M) but did not inhibit PtdIns 4-kinase or tested protein and lipid kinases. Analogs of LY294002 demonstrated a very selective structure-activity relationship, with slight changes in structure causing marked decreases in inhibition. LY294002 was shown to completely abolish PtdIns 3-kinase activity in fMet-Leu-Phe-stimulated human neutrophils, as well as inhibit proliferation of smooth muscle cells in cultured rabbit aortic segments. Since PtdIns 3-kinase appears to be centrally involved with growth factor signal transduction, the development of specific inhibitors against the kinase may be beneficial in the treatment of proliferative diseases as well as in elucidating the biological role of the kinase in cellular proliferation and growth factor response.
Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 mumol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.
In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.
The antimutagenicity of the Citrus flavonoids naringin, hesperidin, nobiletin, and tangeretin against the mutagens benzo[a]pyrene, 2-aminofluorene, quercetin, and nitroquinoline N-oxide was investigated in the Salmonella/microsome assay. Naringin and hesperidin showed a weak antimutagenic activity against benzo[a]pyrene. Tangeretin was antimutagenic against all indirectly-acting mutagens tested, but in general a large molar excess was necessary. Liquid preincubation increased the antimutagenicity of tangeretin against 2-aminofluorene. Nobi-letin acted as an antimutagen against benzo[a]pyrene, but it enhanced the mutagenicity of 2-aminofluorene. However, in a liquid preincubation assay nobiletin also exhibited antimuta-genicity against 2-aminofluorene. Both tangeretin and nobiletin inhibited the mutagenicity of quercetin. Quercetin itself acted as an antimutagen against 2-aminofluorene in a Salmonella strain (TA1538) where its mutagenicity was not expressed. Quercetin should not merely be regarded as a genotoxic risk factor in the human diet, since its mutagenicity may be inhibited by accompanying compounds including other flavonoids, and since quer-cetin itself also exhibits an antimutagenic action. Because of the antimutagenic properties the Citrus flavonoids tested, especially tangeretin and nobiletin, might play a role in the chemopreven-tion of cancer.
This meta-analysis of tea consumption in relation to stroke, myocardial infarction, and all coronary heart disease is based on 10 cohort studies and seven case-control studies. The study-specific effect estimates for stroke and coronary heart disease were too heterogeneous to be summarized (homogeneity p < 0.02 for stroke, p < 0.001 for coronary heart disease). Only the relative risk estimates for myocardial infarction (seven studies) appeared reasonably homogeneous (homogeneity p = 0.20). The incidence rate of myocardial infarction is estimated to decrease by 11% with an increase in tea consumption of 3 cups per day (fixed-effects relative risk estimate = 0.89, 95% confidence interval: 0.79, 1.01) (1 cup = 237 ml). However, evidence of bias toward preferential publication of smaller studies that suggest protective effects urges caution in interpreting this result. The geographic region where the studies were conducted appeared to explain much of the heterogeneity among coronary heart disease, myocardial infarction, and probably stroke results. With increasing tea consumption, the risk increased for coronary heart disease in the United Kingdom and for stroke in Australia, whereas the risk decreased in other regions, particularly in continental Europe. Am J Epidemiol 2001;154:495-503.