Brain, Behavior, and Immunity 23 (2009) 721–731

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Brain, Behavior, and Immunity

journal homepage: www.elsevier.com/locate/ybrbi

Invited Review

Bioactive components of tea: Cancer, inflammation and behavior

Elvira Gonzalez de Mejia a,*, Marco Vinicio Ramirez-Mares b, Sirima Puangpraphant a
a
Department of Food Science and Human Nutrition at University of Illinois, Urbana-Champaign, 228 ERML, MC-051, 1201 W. Gregory Drive, Urbana, IL 61801, USA
b
Resources Institute at University Del Mar, Puerto Angel, Oaxaca, Mexico

a r t i c l e i n f o a b s t r a c t

Article history: Tea is one of the most widely consumed beverages worldwide. Several studies have suggested that cat-
Received 5 January 2009 echins and theaflavins found in tea may reduce the risk of various types of cancers. Major advances have
Received in revised form 21 February 2009 been made to understand the molecular events leading to cancer prevention; however, the evidence is
Accepted 22 February 2009
not conclusive. Evidence from pre-clinical and clinical studies also suggests that persistent inflammation
Available online 1 March 2009
can progress to cancer. Several possible mechanisms of action may explain the cancer preventive aspects
of tea components specifically anti-inflammatory effects. In regards to brain health, green tea catechins
Keywords:
have been recognized as multifunctional compounds for neuroprotection with beneficial effects on vas-
Teas
Polyphenols
cular function and mental performance. Theanine, a unique amino acid in tea, enhances cognition in
Bioactive compounds humans and has neuroprotective effects. Human interventional studies with well characterized tea prod-
Theanine ucts are needed.
Cancer prevention Ó 2009 Elsevier Inc. All rights reserved.
Anti-inflammation
Behavior
Mood
Neuroprotection

1. Introduction introduced in several countries enjoying a semitropical climate.

After water, tea is the most commonly consumed beverage
around the world (Graham, 1992). The origins of tea drinking date
back to 2737 BC (Chow and Kramer, 1990). It is legendarily attrib-
uted to the Chinese emperor Shen Nung, the Divine cultivator who
also apparently invented agriculture and herbal medicine. Tea re-
mained as a primarily Chinese beverage until the 17th century
when Europeans began its trade. It was then introduced to America
in 1650 and in 1904 ‘‘the first iced tea” was served (Clark, 1989).
The objective of this review is to discuss the potential cancer pre-
ventive and anti-inflammatory effects, as well as the impact on
animal and human behavior of tea and tea components.
2. Types of tea
Tea is made from the processed leaf of Camellia sinensis, a plant
cultivated across the world in tropical and subtropical regions. Tea
plants belong to the Theaceae family and come from two main vari-
eties: Camellia sinensis var. sinensis, a small-leaved, bushlike plant
originating from China, grown in several countries of Southeast
Asia experiencing a cold climate, and Camellia sinensis var. assami-
ca, a large-leaved tree discovered in the Assam region of India and
* Corresponding author. Fax: +1 217 244 3198.
E-mail address: edemejia@illinois.edu (E.G. de Mejia).
The assamica variety contains large amounts of tannins and cate-
chins and is particularly used for black tea, whereas sinensis tea ac-
counts for most of the green tea production.
The differences among teas arise from processing, growth con-
ditions, and geography. Tea types, based on processing or har-
vested leaf development are black (fermented), green (non-
fermented), oolong (semi-fermented) and white (harvested leave
buds with white trichomes, non-fermented or semi-fermented).
Green tea is produced by using young tea leaves (bud and two
leaves underneath––a flush). After withering, steaming or pan fir-
ing, drying and grading, the tea is packaged and sold for consump-
tion without fermentation. Pan firing is required to prevent the tea
leaves from fermenting by the natural enzyme activities. To make
black tea, tea leaves are allowed to ferment for several hours before
being either smoke fired, flame fired or steamed. Withering occurs
as water evaporates and the natural process of fermentation takes
place. During fermentation the chemical composition of the tea
leaf is altered (Chow and Kramer, 1990). Unblended teas are
named by their country of origin or region (Darjeeling, Assam, Chi-
na). Blended teas are named generically (Earl Gray, Irish Breakfast)
rather than by the teas they include. Chinese people consume pu-
erh tea; crude green tea is used as a raw material for its prepara-
tion and a long fermentation process. As for the quality and taste
of pu-erh tea, it is believed that the longer preservation period,
the better the quality and taste (Wang et al., 2008).

0889-1591/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.bbi.2009.02.013
722 E.G. de Mejia et al. / Brain, Behavior, and Immunity 23 (2009) 721–731
Aging of the population and limitations of modern medicine
have caused consumers to look for new ways to improve their
health. Tea is now considered a healthy drink with bioactive mol-
ecules and high antioxidant capacity.
3. Phytochemicals in tea
Fresh green tea leaves are rich in flavonoids that include cate-
chin, epicatechin (EC), epigallocatechin (EGC) collectively known
as flavanol monomers, epicatechin gallate (ECG), and epigallocate-
chin gallate (EGCG) which are also called flavanol gallates.
Catechins contain a benzopyran skeleton with a phenyl group
substituted at the 2-position and a hydroxyl (or ester) function at
the 3-position. Variations to the catechin structure include the ste-
reochemistry of the 2,3-substituents and the number of hydroxyl
groups in the B- and D-rings. Oolong and green teas have high lev-
els of EGCG (50–80% of total catechins) and EGC, but the content in
black tea is much lower. Catechins are present at levels of 30–40%
of the dry weight of fresh green tea leaves. Green tea contains
approximately 70% catechins (monomeric flavonoids), 10% minor
flavanols (mainly quercetin, kaempferol, myricetin and their glyco-
sides) and 20% polymeric flavonoids. Because some oxidation oc-
curs during the withering process, 20–30% of total flavonoids in
green tea may be oxidized to polymers such as those found in black
tea. Tea contains several amino acids, but L-theanine (c-glutamyl-
ethylamide), specific to the tea plant, is the most abundant,
accounting for 50% of the total amino acids. Volatile fractions of
tea leave contain more than 600 different molecules. In addition,
tea contains carbohydrates, caffeine, adenine, gallic acids, tannins,
gallotannins, quercetin glycosides, carotenoids, tocopherols,
vitamins (A, K, B, C), small amounts of aminophylline and a yellow
volatile oil that is solid at 25 °C and has a strong aromatic odor and
taste (Jayabalan et al., 2008).
During fermentation of fresh tea leaves, some catechins are oxi-
dized or condensed to larger polyphenolic molecules (dimers or
polymers), such as theaflavins (theaflavin, theaflavin-3-gallate,
theaflavin-30 -gallate and theaflavin-3-30 -digallate) (3–6%) and
thearubigins (12–18%). These polymers are responsible for black
tea’s bitter taste and dark color. Black tea contains mainly thearub-
igins (70%), theaflavins (12%), flavonols (10%) and catechins
(8%). The total polyphenol content of green and black teas is sim-
ilar, but with different types of flavonoids present, due to the de-
gree of oxidation during processing (Stangl et al., 2006). An
average cup of tea (10 g of tea leaves in 1 L water) contains around
300 mg of solids with 30–42% catechins and 3–6% caffeine (Khan
and Mukhtar, 2007).
4. Metabolism and bioavailability
The knowledge of pharmacokinetics, absorption, distribution,
metabolism, and excretion of tea components is essential to deter-
mine its potential bioactivities and overall significance in disease
prevention (Wheeler and Wheeler, 2004). Progress has been made
in understanding biotransformation and bioavailability of the four
major green tea components (EC, ECG, EGC, EGCG); their fate in
animals and in humans depends on intestinal, microbial and hepa-
tic metabolism, as well as their transporters and chemical stability.
Three types of metabolic pathways, methylation, glucuronida-
tion, and sulfation, have been observed for all catechins.
Methylation, a major metabolic pathway, forms the metabolites: 30
and 40 -O-methyl-()-EC and O-methyl-()-EC-glucuronide,
400 -O-methyl-ECG, 40 -O-methyl-EGC, 400 -O-methyl-EGCG and 40 ,
400 -di-O-methyl-EGCG, and 400 -O-methyl-EGCG-30 -O-glucuronide
and 30 ,40 - or 30 ,50 -di-O-methyl-EGCG-4’’-O-glucuronide (Feng,
2006). ()-EC was efficiently sulfated mainly through SULT1A1 in
human liver cytosol. In the intestine, both SULT1A1 and SULT1A3
also contributed to the sulfation. Sulfation of ()-EC was consider-
ably less efficient in the rat than in the human. ()-EC was not glucu-
ronidated by human liver and small intestinal microsomes. There
was also no evidence of glucuronidation by human colon micro-
somes or by recombinant UDP-glucuronosyltransferase-1A7
(UGT1A7), which is present in stomach and esophagus, but not in li-
ver. Interestingly, in rat liver microsomes ()-EC was efficiently glu-
curonidated with the formation of two glucuronides. These results
indicated that sulfation of ()-EC was a major pathway in human li-
ver and intestine with no glucuronidation occurring (Vaidyanathan
and Walle, 2002). Lu et al. (2003) found four EGC-glucuronides (EGC-
30 -O-glucuronide, EGC-7-O-glucuronide, 40 -methyl-EGC-30 -O-glu-
curonide and 40 -methyl-EGC-7-O-glucuronide) and six EGCG
glucuronides (40 -O-methyl-EGCG-glucuronide, 40 ,400 -di-O-methyl-
EGCG-glucuronide, EGCG-7-O-glucuronide, EGCG-30 -O-glucuro-
nide, EGCG-3’’-O-glucuronide and EGCG-4’’-O-glucuronide) when
exposing EGC and EGCG to human, mouse, and rat liver microsomes
and nine different human UGT isozymes . EGCG-4’’-O-glucuronide
was a major metabolite formed in all incubations.
Studies have demonstrated that the absorption of green tea cat-
echins (GTCs) in the small intestine is relatively small. Flavanols ap-
pear to pass through biological membranes and to be absorbed
without deconjugation or hydrolysis. The low absorption in the
small intestine implies that the majority of ingested GTCs will reach
the large intestine where they encounter the colonic microflora,
with further hydrolysis of glycosides into aglycones and extensive
transformation into various aromatic acids (phenylvalerolactones
and hydroxyphenylpropionic acids) (Nakagawa et al., 1997). These
acids are further metabolized to derivatives of benzoic acid. The
microbial metabolites are absorbed and conjugated with glycine,
glucuronic acid, or sulfate (Manach et al., 2004). GTC plasma bio-
availability in humans is very low. After the administration of either
697 mg of green tea or 547 mg of black tea to healthy volunteers,
plasma EGC and EC content was 0.26–0.75% compared with EGCG
and ECG with 0.07–0.20% and the same trend was observed in urine
(Henning et al., 2008). When an individual catechin was used, plas-
ma concentration was reported as high as 1.53 lM at a dose of
1050 mg for ()-EC, 3.1 lM at a dose of 664 mg for ECG, 5 lM at
a dose of 459 mg for EGC and 6.35 lM at a dose of 1600 mg for
EGCG (Feng, 2006).
In human urine, six metabolites were identified as ()-EC-glu-
curonide, three ()-EC-sulfates, two O-methyl-()-EC-sulfates.
Microbial metabolites ()-5-(30 ,40 -dihydroxyphenyl)-c-valerolac-
tone, and their glucuronide conjugates were also found. Although
ECG has been studied, no metabolites were observed in both plas-
ma and urine. In human urine, several metabolites were identified
as EGC-glucuronide, two EGC-sulfates, three O-methyl-EGC-glucu-
ronides, three O-methyl-EGC-sulfates, and 40 -O-methyl-EGC.
Additionally, microbial metabolites ()-5-(30 , 40 ,50 -trihydroxyphe-
nyl)-c-valerolactone, ()-5-(30 ,50 -dihydroxyphenyl)-c-valerolac-
tone, ()-5-(30 ,40 -dihydroxyphenyl)-c-valerolactone, and their
sulfate and glucuronide conjugates from EGC were also found.
For EGCG, several metabolites in human plasma and urine were
identified as: 40 ,4’’-di-O-methyl-EGCG, ()-5-(30 ,40 ,50 -trihydroxy-
phenyl)-c-valerolactone, ()-5-(30 ,50 -dihydroxyphenyl)-c-valero-
lactone, ()-5-(30 ,40 -dihydroxyphenyl)-c-valerolactone, and their
sulfate and glucuronide conjugates (Feng, 2006).
Large and extensively conjugated metabolites are more likely to
be eliminated in the bile, whereas small conjugates such as mono-
sulfates are preferentially excreted in urine. Biliary excretion
seems to be a major pathway for the elimination of EGCG. The total
amount of metabolites excreted in urine is roughly correlated with
maximum plasma concentrations. Urinary recovery was 0.5–6% for
some tea catechins (Yang et al., 2000). The half-lives of flavanols in
plasma are in the order of 2–3 h, except for EGCG, which is elimi-
 E.G. de Mejia et al. / Brain, Behavior, and Immunity 23 (2009) 721–731
nated more slowly probably because of higher biliary excretion or
greater complexing with plasma proteins (Diniz et al., 2008). For
tea catechins with rapid absorption and a short half-life, repeated
intakes must be very close together in time to obtain an accumula-
tion of metabolites in plasma; otherwise, plasma concentrations
regularly fluctuate after repeated ingestions, and no final accumu-
lation occurs (Warden et al., 2001).
The nature of the tissular metabolites may be different from
that of blood metabolites because of the specific uptake or elimina-
tion of some of the tissular metabolites or because of intracellular
metabolism (Youdim et al., 2003). An intervention study with
green and black tea confirmed the presence of gallated and nongal-
lated flavan-3-ols in human prostate after 1 week of daily con-
sumption of 5 cups of tea; EGC was found after green tea and
black tea intervention (Henning et al., 2006).
Adverse events associated with high flavanol intake are rare,
which may be explained by their relatively low absorption, and their
rapid metabolism and quick elimination. Cancer patients, consum-
ing 6 g/day of a caffeinated green tea extract in three to six equal
doses, reported mild to moderate nausea, abdominal pain and diar-
rhea, along with agitation, insomnia, dizziness and tremors, likely
due to the caffeine content (Jatoi et al., 2003). The above would sug-
gest that relatively large amounts of flavanols are well tolerated. At
present, it would seem that a safe upper limit of chronic intake is on
the order of one gram or more of flavanols per day.
5. Quality and standardization
The quality of a tea is mainly assessed through its appearance
(color, color intensity, and cloudiness), its flavor (astringency, bit-
terness, and sweetness), and its aroma (floral, sweet, grassy). Bit-
terness and astringency are attributed from alkaloid caffeine and
catechin (tannins), respectively. Sweetness is attributed to amino
acids, especially theanine, which has the taste described as
‘‘umami” or ‘‘brothy” or 5-N-ethylglutamine. The appearance of
the leaves and the color of the brew play a major role in the eval-
uation of green tea; young leaves and a clear brew with a pale
green–yellowish tint are indicators of high quality. The quality of
a green tea declines with signs of cloudiness and brown–reddish
pigments. Green teas of different origin have their distinctive char-
acters, but in general, high quality green teas are described as ‘‘del-
icate” or ‘‘sweet”. The highest quality tea from Japan, called
Gyokuro (pulverized for ceremonial tea ‘‘Matcha”), is grown under
shade, and is reported to contain high amino acid but low catechin
concentration (Willson, 1999). Theaflavins, thearubigins, catechins,
and caffeine are known to be responsible for black tea quality;
green tea quality depends more on content of amino acids, cate-
chins, and caffeine. Qualitative and quantitavive methods have
been used to evaluate active compounds involved in the quality
assessment of green tea (Gall et al., 2004; Fujiwara et al., 2006),
including principal component analysis and partial least-squares
projection to latent structure analysis based on gas chromatogra-
phy/mass spectrometry/metabolomics (Pongsuwan et al., 2007).
Teas are natural products and thus do not have a consistent, stan-
dardized composition. Batch-to-batch and manufacturer-to-manu-
facturer variation in preparations of the same tea will occur.
Several manufacturers now produce standardized tea extracts
(based on an active ingredient) as an approach to achieving more
consistent quality, at least within manufacturer. Manning and Rob-
erts (2003) found wide variability and much lower amounts in 5
catechins compared to claims on the labels. It is recommended that
phytochemicals in dietary supplements should be standardized so
that consumers can make a rational choice; however, due to large
number of organic compounds present in tea, it is difficult to pro-
cess tea to an absolute standard (Heinrich et al., 2004).
723
Interest in tea and tea extracts as dietary supplements, arises
from the fact that some tea compounds have beneficial protective
effects against chronic diseases (Chen et al., 2008). However, the
effectiveness of any tea from a pharmacological perspective de-
pends upon providing an effective dosage of the standardized ac-
tive compounds.
6. Studies on tea and human cancer
One third of the human cancers are caused by dietary habits
and manipulation of the diet is recognized as a potential strategy
against this disease. Chemoprevention has emerged as a practical
approach to reducing cancer incidence and therefore the mortality
and morbidity associated with it. An ideal chemopreventive agent
for humans should have minimal side effects, high efficacy in mul-
tiple sites and a known mechanism of action. In addition, it should
be nontoxic to normal cells, capable of oral consumption, inexpen-
sive, sufficiently bioavailable and with human acceptance.
The use of tea, as a cancer chemopreventive agent has been
appreciated in the last twenty years. Epidemiological as well as
laboratory studies have shown an inverse association of tea con-
sumption with the development of certain cancer types (Artali
et al., 2009; Mann et al., 2009; Kuo et al., 2009). The first epidemi-
ological report indicating an association between tea composition
in humans and cancer was published in 1966 (Higginson, 1966).
It has now been suggested that tea polyphenols potently induce
apoptotic cell death and cell cycle arrest in tumor cells but not in
their normal cell counterparts and affect several biological path-
ways (Chen et al., 2008). As supporting evidence, various animal
studies have revealed that treatment with tea inhibits tumor inci-
dence and multiplicity in different organ sites such as skin, lung,
liver, stomach, mammary gland, and colon (Chen et al., 2008).
Most of the research related to cancer prevention by tea has been
done with flavanols; although, caffeine is another bioactive compo-
nent in green and black teas. There are some studies that attribute a
chemopreventive effect to caffeine. For instance, Chung et al. (2003)
found that a black tea preparation was effective in inhibiting
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced
lung tumorigenesis in F344 rats, and concluded that caffeine appears
to be the major chemopreventive component. Huang et al. (1997)
reported that orally administered decaffeinated green and
black teas, were much less effective than the caffeinated teas in
reducing the incidence and multiplicity of UVB light-induced skin
tumors in SKH-1 mice. Also, Castro et al. (2008) demonstrated that
administration of caffeine to pregnant and nursing B6129SF1 female
mice exposed to dibenzo[a,l]pyrene (DBP), provided cancer chemo-
prevention for her offsprings. In humans, there are insufficient
studies to make any meaningful conclusion on the role of caffeine
in tea on cancer protection.
Other studies have also demonstrated the inhibitory action of
green and black teas against tumorigenesis in animal models and
on different organ sites such as skin, oral cavity, lung, esophagus,
small intestine, stomach, liver, colon, bladder, pancreas, mammary
gland, and prostate. Recent reviews on this subject present results
of pre-clinical studies on tea and cancer prevention, using different
animal models (Yang et al., 2007; Ju et al., 2007; Lambert et al.,
2005).
There are several human studies which support a positive effect
of tea consumption and cancer. Stages I and II breast cancer pa-
tients (n = 472) showed a lower recurrence rate (16.7%) and a long-
er disease-free period (3.6 years) when consuming more than five
cups of green tea per day, compared to those consuming fewer
than four cups per day (Nakachi et al., 1998). Pisters et al. (2001)
carried on a phase I trial of oral green tea extract (GTE) and con-
cluded that a dose of 1850 mg GTE three times daily could be taken
724 E.G. de Mejia et al. / Brain, Behavior, and Immunity 23 (2009) 721–731
safely for at least 6 months. Green tea consumption was inversely
associated with rate of recurrence, especially in early stages of
breast cancer (Nakachi et al., 1998; Inoue et al., 2001). According
to Wu et al. (2003a,b), regular green tea drinkers (90 mL per day)
showed a significant reduced risk of breast cancer compared to wo-
men who had tea less than once a month. Zhou et al. (2004) also
reported that breast cancer is significantly less prevalent among
Asian women, whose diets contain high intake of green tea. In a
case-control study with breast cancer confirmed patients
(n = 1009 female aged 20–87 years), green tea consumption was
associated with a reduced risk of developed breast cancer (Zhang
et al., 2007). Yamamoto et al. (2003) reported that green tea poly-
phenols (GTP) could be used to enhance the effectiveness of che-
mo/radiation therapy to promote cancer cell death while
protecting normal cells. A case-control study demonstrated a de-
clined risk of prostate cancer with increasing frequency, duration
and quantity of green tea consumption suggesting intake of three
cups per day (Jian et al., 2004). Consumption of green tea catechin
capsules after one year inhibited the conversion of high-grade
prostate intraepithelial neoplasia to cancer, in comparison to a pla-
cebo (Bettuzzi et al., 2006). Consumption of green tea assessed by a
questionnaire (n = 49,920 men aged 40–69 years) was associated
with a dose-dependent decrease in the risk of advanced prostate
cancer (Kurahashi et al., 2008). Another study showed that the dai-
ly consumption of green tea over a period of 10 years delayed the
onset of cancer in both smokers and nonsmokers (Nakachi et al.,
2000). A randomized controlled tea intervention phase II trial re-
vealed a significant decrease (p = 0.002) in urinary 8-hydrox-
ydeoxyguanosine (31%) after drinking decaffeinated green tea (4
cups/day) among smokers over a 4 month-period (Hakim et al.,
2003). These data suggest that regular green tea drinking might
protect smokers from oxidative damage and could reduce risk for
cancer caused by free radicals associated with smoking. Arts
(2008) reviewed epidemiological evidence on tea consumption
and found a significant lower risk of lung cancer associated with
a high intake of black or green tea especially among never smokers.
Sun et al. (2002) investigated the association between urinary
tea catechin markers and subsequent risk of gastric and esophageal
cancers in Chinese. It was found that the urinary EGC showed a sta-
tistically significant inverse association with gastric cancer. Yuan
et al. (2006) also found an association between biomarkers (EGC
and 4-MeEGC) of tea consumption in urine and a lower risk of
developing colorectal cancer (n = 18,244 men with 16 years of fol-
low-up). Borrelli et al. (2004) concluded in a systematic review
that an inverse association for green tea did show a protective ef-
fect on adenomatous polyps and chronic gastritis. In the same way,
Hoshiyama et al. (2004) indicated that green tea consumption had
no protective effect against stomach cancer, and suggested the
implication of other factors such as age, smoking and socioeco-
nomic status. Cabrera et al. (2006) published a very comprehensive
review on epidemiological studies of the association between
green tea consumption and cancer risk concluding that there are
several confounding factors that were not considered and there
is a need to assess specifically green tea consumption. Conflicting
results between cohort studies conducted in different countries
may also arise from uncertainty in the frequency and timing of in-
take, and contrasts in the socioeconomic and lifestyle factors asso-
ciated with tea drinkers (Cabrera et al., 2006). The kind of tea or its
preparation (e.g., brewing time and tea temperature) will have an
impact on type and concentration of polyphenols. Definitive con-
clusions concerning the protective effect of tea have to come from
well-designed observational epidemiological studies and interven-
tion trials.
A number of epidemiological and clinical studies have revealed
various physiological responses to green tea which may be rele-
vant to the promotion of health and the prevention of cancer. How-
ever, based on human studies, the Food and Drug Administration
concluded in 2005 that there was highly unlikely that green tea re-
duces the risk of breast cancer and the risk of prostate cancer, and
that there was no credible evidence supporting a relationship be-
tween green tea consumption and gastric, lung, and colon/rectal
cancer. Also, the American Institute for Cancer Research (2007)
concluded that evidence from human studies was too limited to
draw any conclusions of the relationship between green tea con-
sumption and cancer prevention. Research in this area, however,
continues; particularly in regards to the mechanisms of action.
Khan and Mukhtar (2008) highlighted the pathways related to
cancer chemoprevention by GTP, specially EGCG as causing inhibi-
tion of: (1) mitogen-activated protein (MAP) kinases and activator
protein-1 (AP-1), (2) nuclear factor-jB (NF-jB) signaling pathway,
(3) epidermal growth factor receptor (EGFR)-mediated pathways,
(4) insulin-like growth factor (IGF)-1 mediated signal transduction
pathway, (5) proteosome activities, (6) matrix metalloproteinases
(MMPs), (7) urokinase-plasminogen activator, and (8) induction
of apoptosis and cell cycle arrest. Authors concluded that the rele-
vance to humans lies in the fact that these markers, as well as the
identification of further molecular targets and biomarkers, are
needed to allow a better design of clinical trials with green and
black teas and their components. It is also believed that the chemo-
preventive effects of green tea depend on: (1) antioxidant action;
(2) specific induction of detoxifying enzymes; (3) molecular regu-
latory functions on cellular growth, development and apoptosis;
and (4) selective improvement in the function of the intestinal bac-
teria flora. The effect of tea consumption and cancer prevention
will need to be re-evaluated in the future as new data becomes
available.
As anti-inflammatory agents are used in chemopreventive strat-
egies, this review will discuss the association between inflamma-
tion and tea consumption.
7. Studies on tea and inflammation
Cytokines are a group of multifunctional proteins that mediate
and are involved in several steps related to inflammatory re-
sponses. Inflammatory cytokines are signaling proteins expressed
in a number of tissues, notably monocytes/macrophages, vascular
endothelial cells, adipose tissue, and neurons. Inflammatory cyto-
kines respond to injury or infection and have broad effects on
the organism including fever and inflammation, and promote
wound healing. The secreted cytokines bind to their own receptors
and exert their effect on target cells. Generally, cytokines can be
classified as pro- or anti-inflammatory, depending on the way they
influence inflammation (Kundu and Surh, 2008).
Cytokines such as tumor necrosis factor-a (TNF-a), IL-6, IL-1,
GM-CSF, interferon-c (IFN-c), and IL-12 are critical in the induction
of the inflammatory response. The induction of pro-inflammatory
genes by TNF has been linked to most diseases including cancer
(Kundu and Surh, 2008). The pro-inflammatory effects of TNF are
primarily due to its ability to activate nuclear factor kappa B (NF-
jB). Almost all cell types, when exposed to TNF, activate NF-jB,
leading to the expression of inflammatory genes such as cyclooxy-
genase-2 (COX-2), lipoxygenase-2 (LOX-2), cell-adhesion mole-
cules, inflammatory cytokines, chemokines, and inducible nitric
oxide synthase (iNOS).
Some of the cytokines however, have down-regulating effects
on inflammation such as, transforming growth factor-b (TGF-b),
IL-10, IL-4, IL-13 and are known as anti-inflammatory cytokines
(Chi et al., 2006). Furthermore, a number of cytokines have the
ability to promote migration of leukocytes into inflammatory sites,
and are described as chemokines (Kundu and Surh, 2008). Exam-
ples of these are IL-8, and growth regulated oncogene-a (Gro-a).
 E.G. de Mejia et al. / Brain, Behavior, and Immunity 23 (2009) 721–731
Recent evidence has indicated that cytokines are involved in the
pathophysiology of many inflammatory diseases (Kundu and Surh,
2008). These pathological states seem to be linked to an imbalance
of the cytokine network and the excessive recruitment of leukocytes
to the inflammatory sites (Chi et al., 2006). Because of this, the cyto-
kine system constitutes a very interesting and promising target for
the development of anti-inflammatory drugs (Holfseth, 2008). It
was found that phytochemical compounds in tea are able to selec-
tively interfere with the production and/or function of cytokines.
This interesting observation would constitute an important alterna-
tive for the treatment of several inflammation related diseases.
Effects of polyphenols such as anti-inflammatory, anti-tumor,
and anti-atherogenic could not be explained solely on the basis
of their antioxidant properties. Investigations into the mechanism
of action of these molecules have shown that polyphenols modu-
late cellular signaling processes during inflammation or may them-
selves serve as signaling agents (Rahman et al., 2006).
Table 1 outlines a summary of the anti-inflammatory properties
of tea polyphenols to give a general idea of the wide variety of cel-
lular inflammatory processes that such compounds can modulate.
Among the numerous polyphenols isolated from green tea, EGCG
predominates and has been shown to possess anti-inflammatory
properties in animal and in vitro models (Hamer, 2007). The effects
of tea polyphenols on inflammation have also relevance to cancer
prevention (Beltz et al., 2006). Tea polyphenols appear to modulate
at different targets the anti-inflammatory activities related to ara-
chidonic acid-dependent pathways such as COX inhibition. Within
the arachidonic acid-independent pathways, NOS and NF-jB are
targets of polyphenols (Miles et al., 2005). Tea phytochemicals in-
hibit COX-2 and iNOS expression by blocking NF-jB activation.
Particularly EGCG suppresses activation of NF-jB by repression
of degradation of the inhibitory unit IjBa, which hampers subse-
quent nuclear translocation of the functionally active subunit of
NF-jB (Kundu and Surh, 2008).
Based on current evidence, tea polypenols can modulate cancer
risk through suppression of chronic inflammation that seems to
pervade many cancers (Fig. 1). The evidence suggests that tea com-
ponents protect against inflammation and cancer at the molecular,
cellular, and animal levels. Current evidence also suggests that
stress can affect the development and progression of cancer (Ar-
maiz-Pena et al., 2009; Metcalfe et al., 2007; Ben-Eliyahu et al.,
2007). For instance, Yang et al. (2009) showed that when human
melanoma cells were treated with the catecholamine stress hor-
mone norepinephrine (NE), the angiogenic potential of these tumor
cells was stimulated by the production of the vascular endothelial
growth factor (VEGF) and interleukins (IL)-8 and IL-6. Thaker et al.
(2006) established, in an orthotopic mouse model, that the release
of catecholamines induced by stress can activate the b2 adrenergic
receptor on ovarian carcinoma cells to elicit increased expression
of the VEGF gene, which resulted in enhanced tumor vasculariza-
tion. Recent studies have suggested that tea consumption may be
associated with a reduction of psychological and physiological re-
sponses to stress, such as lower post-stress cortisol levels, inhibi-
tion of cortical neuron excitation, lower lipid peroxide levels,
reduced food intake and decrease DNA damage (Steptoe et al.,
2007a; Kimura et al., 2007; Kurihara et al., 2003; Yamada et al.,
2008; Hakim et al., 2008).
8. Tea and behavior
Green tea polyphenols, especially EGCG, have shown neuropro-
tective activities in a wide array of cellular and animal models of
neurological disorders. For instance, in orally treated mice, green
tea EGCG had anti-inflammatory and neuroprotective capacities
(Aktas et al., 2004). Also, simultaneous administration of catechins
725
(Polyphenon 70STM, 80% pure, containing 31.7% EGCG, 15.7% EGC,
10% ECG, 8.5% EC, 4.5% GCG and 1% CG, and no caffeine) plus doco-
sahexaenoic acid (an important component of fish oil) enhanced
brain function in both adult and old mice (Shirai and Suzuki,
2004). A 0.02% of a catechin preparation (Polyphenol 70STM) pre-
vented the decline of glutathione peroxidase activity, reduced pro-
tein oxidative damage in brain and maintained its function in the
aging mouse (Kishido et al., 2007). Catechins, provided as water
containing EGCG (63%), EC (11%), EGC (6%), and ECG (6%), improved
working memory-related learning ability and special orientation in
rats (Haque et al., 2006).
Tea has been shown to reduce physiological stress responses
and increase relaxation ratings (Steptoe et al., 2007a) when com-
pared with coffee or other beverages matched for caffeine level.
Mandel et al. (2008) observed that tea consumption was inver-
sely associated with the incidence of age related dementia, Alzhei-
mer’s and Parkinson’s diseases showing that tea polyphenols,
particularly EGCG, are bioavailable to the brain and can act at mul-
tiple targets, via antioxidant, iron-chelation, signal transduction
modulation, and other mechanisms to produce neuroprotective
and/or neurorescue action. Mandel et al. (2008) suggested a model
for EGCG neuroprotective/neurorestorative action that goes be-
yond antioxidant/radical-scavenging capacity, including activation
of protein kinase C signaling pathways preventing apoptosis and
mitochondrial membrane collapse. The model also included activa-
tion of other signaling pathways, important in neuronal protection
against extracellular insults and essential for neuronal differentia-
tion and survival, particularly the mitogen-activated protein ki-
nases (especially the ERK1/2 pathway), phosphatidylinositide 30 -
OH kinase/AKT and protein kinase A signaling cascades, and cell
calcium influx regulation. Agents such as flavonoids in green tea
are capable of inducing pathways leading to activation of the tran-
scription factor cAMP-response element-binding protein (CREB)
with the potential to enhance both short-term and long-term
memory. In contrast to short-term memory, the storage of long-
term memory requires the formation of stable long-term potentia-
tion at synapses. It is also believed that green tea catechins are
multimodal-acting, brain-permeable, natural iron chelators, anti-
oxidants acting at multiple brain targets to prevent or delay neuro-
nal death in the degenerating brain (Mandel et al., 2005).
Black tea ingestion seemed to produce a rapid increase in alert-
ness and self-reported improvements in mood (Hindmarch et al.,
1998; Quinlan et al., 2000). The capacity to process information
was also increased, while adverse effects on sleep duration or qual-
ity were not evident. As tea is not a high caffeine drink, factors
other than caffeine may be influencing these results, for example,
a specific psychological response to tea drinking or other constitu-
ents in tea. One of these components is theanine, which could act
as a neurotransmitter with neuroprotective effects. A study in rats
found that theanine modulated serotonin and dopamine levels and
appeared to improve memory and learning ability (Unno et al.,
1999). It was also suggested that theanine increased neurotrophin
mRNA levels by activating inhibitory neurotransmitter systems
and promoted CNS maturation assisting in brain function develop-
ment (Yamada et al., 2007). Matching electroencephalographic
recordings with cognitive task performance, it has been demon-
strated that the unique tea amino acid theanine plays a role in
attentional processing, in synergy with caffeine, enhancing cogni-
tion in humans (Kelly et al., 2008). Caffeine acts mainly upon the
central nervous system, stimulating wakefulness, facilitating ideas
association and decreasing the sensation of fatigue (Smith, 2002);
however evidence exist that caffeine alone cannot fully account
for the positive effects of tea drinking. Some of the effects caused
by caffeine are influenced by theophylline tea content because it
induces psychoactive activity and it also has a vasodilator effect
(Cabrera et al., 2006).
726 E.G. de Mejia et al. / Brain, Behavior, and Immunity 23 (2009) 721–731

Table 1
Summary of anti-inflammatory activities of tea and tea components.
Type of Compound Proposed target Results Ref.
study molecules
In vitro EGCG IL-6 EGCG (101-103 mg/ml) suppressed IL-6 in cultured Xia et al.
human keratinocytes (2005)
EGCG IL-8 EGCG (3–100 lM) suppressed IL-8 in human lung Chen et al.
epithelial (A549) cells (2002)
EGCG CD11b EGCG (100 lM) down regulated CD11b expression on Kawai et al.
CD8+ T cells (2004)
EGCG TNF-a, IL-1b, IKK EGCG (3–100 lM) inhibited TNF-a and mediated Wheeler et al.
activation of the nuclear factor-jB (NF-jB) pathway, (2004)
through inhibition of IjB kinase (IKK) in human lung
epithelial (A549) cells
EGCG IL-8, MIP-3a, PGE2 EGCG (50 lM) inhibited the synthesis of IL-8, MIP-3a, Porath et al.
and PGE2 in human colon adenocarcinoma cell lines (2005)
HT29 and T84
EGCG IL-2, TNF-a and EGCG (10–100 lM) pretreatment or co-treatment to Watson et al.
IFN-c in T cells murine lymphonode cells (Balb/C). EGCG suppressed the (2005)
production of pro-inflammatory cytokines (IL-2, TNF-a,
IFN-c) in T cells
EGCG NF-jB EGCG (20 lM) suppressed TNF-a-induced NF-jB Navarro-Perán
activation, the phosphorylation and degradation of IjBa et al. (2008)
and the phosphorylation of Akt in human colon
carcinoma cell line (Caco-2)
EGCG IL-1b EGCG (10, 50, and 100 lM) suppressed IL-1b in MUC5AC Kim et al. (2008)
(mucus hypersecretion) and normal human nasal
epithelial (NHNE) cells by suppression of the
phosphorylation of ERK MAP kinase, MSK1, and
transcription factor, cAMP-response element-binding
protein
Green tea extract iNOS Green tea extract (40 lg/mL) inhibited iNOS expression Tedeschi et al.
in human epithelial cell lines, alveolar A549/8 and colon (2004)
DLD-1 cells by down-regulation of the DNA binding
activity of STAT-1a
Black and green teas, iNOS, NO Both green tea and black tea (0.5 mg/mL) reduced NO by Paquay et al.
Theaflavins, EGCG suppress the LPS mediated induction of iNOS in rat (2000)
pulmonary macrophage cell line (NR8383)
Green tea polyphenols, NOS activity, NO Green tea polyphenols (0.5 mg) and tannic acid Srivastava et al.
tannic acid (0.5 mM) inhibited 12-O-tetradecanoyl phorbol 13- (2000)
acetate (TPA)-induced NO generation and NOS activity
in rat hepatocytes
Green, paochong, iNOS, NO Green, paochong, and black teas (500 lg/mL) inhibited Lin et al.
and black teas NO production, iNOS catalytic activity and iNOS protein (2006)
expression in LPS-activated RAW 264.7cells
Catechin TNF-a Catechin (31 lM) inhibited TNF-a production on LPS/ Wang and Mazza
IFN-c-activated RAW 254.7 macrophages (2002)
Black and green teas NO, peroxynitrite Both black and green teas (100 mg/mL) had minor and Heijnen et al.
nonspecific effect on NO mediated vasorelaxation (good (2000)
NO). This study showed that tea separates effects
between the good and bad NO and tea is likely to
prevent NO toxicity primarily
Theaflavin TNF-a, IL-8, NF-jB, and AP-1 Theaflavin treated to human lung adenocarcinoma cell Aneja et al.
line (A549) at concentrations of 10 and 30 lg/mL, (2004)
showed inhibition to tumor through the suppression of
IL-8 transcription and by inhibition of IKK and AP-1
pathways
EGCG, EGC, ECG, Thromboxane (TBX), 12- EGCG, EGC, ECG and theaflavins (30 lg/mL) inhibited the Hong et al.
Theaflavins hydroxyheptadecatrienoic formation of TBX, HHT, COX-2 and PGE2 in normal (2001)
acid (HHT), COX-2, PGE2 human colon mucosa and colon cancer cells
Green and black tea IL-6, TNF-a, IL-1-b, IL-8, Both black tea and green tea extracts (2.5%) treated to Pajonk et al.,
extracts PGE2, and chymotryptic human monocytes isolated from buffy coats decreased 2006
26S proteasome activity LPS-induced IL-1b, IL-6, IL-8, TNFa and PGE2. Black tea
and green tea extracts (0.5% and 2%, respectively)
treated to RAW 264.7 macrophages inhibited
chymotryptic 26S proteasome activity
Green tea polyphenol NF-jB Green tea polyphenol extracts (0.1–0.4 mg/mL) inhibited Yang et al.
extracts, EGCG the phosphorylation of IjBa resulting in a reduction in (2001)
NF-jB activation in the fetal rat intestinal epithelial
(IEC-6) cell line. EGCG (100 lM) inhibited NF-jB by
blocking IKK activity
Theaflavin-3, NF-jB, iNOS TF-3 (30 lM) inhibited IKK activity in LPS-induced Pan et al.
30 -digallate murine macrophages (RAW 264.7), prevented the (2000)
(TF-3) degradation of IjBa and IjBb, blocked phosphorylation
of IjB from the cytosolic fraction, inhibited NFjB
activity, and inhibited iNOS levels
 E.G. de Mejia et al. / Brain, Behavior, and Immunity 23 (2009) 721–731 727

Table 1 (continued)

Type of study Compound Proposed target Results Ref.

molecules

In vivo Tea catechin iNOS, peroxynitrite Male Wistar rats were given 0.5% tea catechin extract for Suzuki et al.
extract 5 days. Catechin blocked serum NOx concentration in (2004)
the jugular vein, and also reduced plasma lipid peroxide
level
EGCG iNOS, NO EGCG (50–200 lM), treated to rat peritoneal Alvarez et al.
macrophages stimulated with sodium, blocked the (2002)
production of NO
EGCG NO, iNOS EGCG (50 and 75 mg/kg) were administered in mice Chen et al.
treated with carbon tetrachloride, caused liver necrosis. (2004)
EGCG decreased iNOS, nitrotyrosine, and NO levels
EGCG NO, malondialdehyde (MDA), EGCG (50 mg/kg/d) was orally treated to male rats’ acid- Ran et al.
superoxide dismutase (SOD), induced colitis for 7 days. EGCG decreased NO, MDA, and (2008)
TNF-a, IFN-c, NF-j Bp65 increased SOD. Modulated mucosal inflammation by
inhibiting the production of TNF-a, IFN-c and NF-jBp65
and may be a potential therapeutic agent in colitis
EGCG NF-j B, AP-1 Mice were treated twice daily with EGCG (10 mg/kg). Abboud et al.
EGCG inhibited NF-jB and AP-1. This may be beneficial (2008)
in colitis through selective immunomodulatory effects
Green tea extracts Serum albumin levels Green tea extracts (20 g/L) reduced serum albumin in Kaori et al.
mouse model infected with Trypanosoma brucei which (2008)
is a tissue invasive parasite that causes mice to develop
extensive tissue damage
Green tea extracts Nitrotyrosine, TNFa Rats were administered with green tea extracts (10 or Muià et al.
20 mg/kg) 15 min prior or post to reperfusion. Green tea (2005)
extracts reduced nitrotyrosine formation and the
production of TNFa. This study showed that green tea
extract significantly reduces ischemia/reperfusion injury
of the intestine
Theaflavin mixture: theaflavin, IL-1b, IL-6, PGE2, Theaflavin mixture (10 lL) was applied to mouse ears Huang et al.
theaflavin-3-gallate, theaflavin- leukotriene B4 (LTB4) 20 min prior to TPA application once a day for 4 days. (2006)
30 gallate, and theaflavin-3, Theaflavins inhibited TPA-induced edema of mouse ears
30 digallate as well as inhibited TPA-induced increase in IL-1b and
IL-6 protein levels. Theaflavins also decreased amount of
PGE2 and LTB4 levels
Green tea polyphenols IFN-c, TNF-a Mice model of chronic inflammatory bowel disease (IBD) Varilek et al.
were fed with green tea polyphenols (5 g/L) for up to (2001)
6 weeks. Green tea polyphenols showed a decrease in
IFN-c and TNF-a. Mice treated with green tea
polyphenols had less severe colitis
Black tea extracts Rat paw oedema Black tea extract was given orally (2.5 and 5 ml/kg) to Nag Chaudhuri
(Sikkim variety) different groups of rats and mice. Tea extract et al. (2005)
significantly inhibited carrageenin, histamine, serotonin
and prostaglandin-induced pedal inflammation
Indian black tea Rat paw oedema Rats and mice were administered orally with Indian Roy et al.
(Himalayan variety) black tea (200 mg/kg and 1000 mg/kg). Treated group (2008)
significantly reduced carrageenin-induced paw oedema
Epidemiological Tea C-reactive protein (CRP), Data from a large cross-sectional study (BELSTRESS) De Bacquer
serum amyloid A (SAA), indicated that of all participants (1031 healthy men), et al. (2006)
serum haptoglobin 22% consumed tea regularly and 10% drank more than
two cups per day. Tea drinkers had significantly lower
levels of CRP, SAA and haptoglobin. This suggested that
drinking tea might help in reducing the inflammatory
process of cardiovascular disease
Black tea Platelet activation, plasma Healthy non-smoking men (n = 37, 18–55 years) were Steptoe et al.
C-reactive protein (CRP) randomized to 6 weeks black tea extract (1050 mg/day). (2007b)
Treatment was equivalent to drinking four cups of
strong black tea per day. Chronic tea consumption
presented lower platelet activation (platelet–monocyte
aggregates, platelet–neutrophil aggregates and total
platelet–leukocyte aggregates), and plasma CRP
compared with placebo. This study suggested that black
tea has anti-inflammatory effects that may protect
against cardiovascular disease development

Six studies were reviewed by Gardner et al. (2007) concluding
that there is weak evidence, due to the low number of participants,
suggesting increased mood and improved cognitive performance
when black tea was consumed. A moderate caffeine intake from
tea appeared to improve mental performance, although sample
size in the studies was small. More work on humans is needed to
confirm these findings.
It has been suggested that dietary flavonoids, potent bioactive
molecules in tea, may exert beneficial effects in the central nervous
system by protecting neurons against stress-induced injury, by
suppressing neuroinflammation and by promoting neurocognitive
performance, through changes in synaptic plasticity (Spencer,
2007, 2008). Flavonoids are potent bioactive molecules by their
ability to interact with a number of neuronal proteins and lipid
728 E.G. de Mejia et al. / Brain, Behavior, and Immunity 23 (2009) 721–731

Fig. 1. A simplified diagram of the suggested roles of tea components on reduction of inflammation, cancer and improved behavior. Tea flavanols have anti-inflammatory
activity, inhibit COX-2 and iNOS expression by blocking NF-jB activation, and act as blocking and suppressing agents of multistage carcinogenesis. Tea catechins act at
multiple brain targets to prevent or delay neuronal death and theanine has been related to improve attention processing and reduce stress.

kinase signalling cascades. A clear understanding of their mecha-
nisms of action as modulators of cell signaling will be crucial in
the evaluation of their potential to act as inhibitors of neurodegen-
eration or as modulators of brain function and consequently bene-
ficial to human memory and neuro-cognitive performance.
In a community-based comprehensive geriatric assessment
(n = 1178), there was an inverse, dose–response, significant associa-
tion between green tea consumption and cognitive impairment
probably due to the presence of tea polyphenols (specially EGCG)
and to some degree to vitamin C and caffeine (Kuriyama et al.,
2006). The contribution of caffeine appears to be small because of
the null relation observed between consumption of coffee and cogni-
tive impairment. More recently, Ng et al. (2008) found a strong in-
verse relationship for black tea consumption and cognitive
impairment. Nurk et al. (2009) used a self-reported questionnaire
in a cross sectional study (n = 2031 aged 70–74 years) in relation to
cognitive test performance and intake of flavonoid-rich foods such
as chocolate, wine and tea. The mean intake of tea was 222 mL/day
without specifying the type of tea consumed or the preparation
method. It was suggested that intake of flavonoid-rich foods, includ-
ing tea, was associated with better performance across several cog-
nitive abilities and the associations were dose–dependent.
9. Conclusions
Human studies are still contradictory and not final conclusions
can be drawn on the effect of tea consumption and cancer preven-
tion. While experimental models have suggested that flavonoids
attenuate cancer risk, epidemiological studies have not conclu-
sively demonstrated a clear effect for tea and lowering cancer risk,
although there is moderate evidence for a slightly positive effect of
black tea consumption on colorectal cancer.
Flavonoids may be capable of exerting antioxidant effects in hu-
mans with the possibility of direct radical scavenging, down regu-
lation of radical production, elimination of radical precursors such
as hydrogen peroxide, metal chelation, inhibition of xanthine oxi-
dase or elevation of endogenous antioxidants. Human studies on
cancer prevention have been limited by sample size and insuffi-
cient control of confounder factors. However, the available evi-
dence for tea polyphenols supports their advancement into phase
III clinical intervention trials aimed at the prevention of progres-
sion of prostate intraepithelial neoplasia, leukoplakia or premalig-
nant cervical disease. Further mechanistic insights are needed as
well as an accurate knowledge of the concentration of flavonoids
and their metabolites in humans.
On the other hand, important advances have been made in
understanding the influence of behavioral factors on inflammation
and cancer initiation and progression, but further research is
needed to completely understand the complex underlying signal-
ing that is driving malignant growth (Armaiz-Pena et al., 2009).
The biological mechanisms related to the chemopreventive activi-
ties of polyphenols are believed to occur by the regulation of sig-
naling pathways such as NF-jB, activator protein-1 or MAPK
kinases. By modulating cell signaling pathways, polyphenols acti-
vate cell death signals and induce apoptosis in precancerous or
malignant cells resulting in the inhibition of cancer development
or progression. Polyphenols can also behave as detoxifying enzyme
inducers, modulating gene expression including induction of phase
II enzymes, such as glutathione S-transferases and quinone reduc-
tase, which usually leads to protection of cells/tissues against
exogenous and/or endogenous carcinogenic intermediates. Phase
II gene inducers also activate MAPK kinases that are involved in
the transcription activation of antioxidant response element-med-
iated reporter gene.
 E.G. de Mejia et al. / Brain, Behavior, and Immunity 23 (2009) 721–731
Tea catechin EGCG prevents hippocampal neuronal cell death in
rats through its antioxidant capacity; reduces oxidative stress in
areas involved in learning and memory, reduces adverse neurobe-
havioral consequences, at least in part, from oxidative stress and
inflammatory signaling cascades. There is evidence supporting
the localization of flavonoids within the brain, thus these tea phy-
tochemicals may be regarded as potential neuroprotective, neuro-
modulatory or anti-neuroinflammatory agents. Evidence indicates
that such beneficial properties are mediated by their abilities to
interact with both protein and lipid kinase signaling cascades.
The concentration of flavonoids encountered in vivo is sufficiently
high to exert pharmacological activity at receptors, kinases and
transcription factors. However, precise sites of action need further
research.
It has been suggested that a high consumption of green tea, a
drink with little toxicity and no caloric content, can be associated
with a lower prevalence of cognitive impairment in humans, and
could have considerable clinical and public health relevance. More
than one to six cups of green tea per day increase plasma antioxi-
dant capacity. Tea has been regarded as ‘‘producing vigor of body,
contentment of mind, and determination of purpose”. Research has
extended beyond inflammation, cancer prevention to cognitive
function and mood. Certainly, tea consumption contributes to a
‘‘sense of social well-being”.
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