Journal of the American College of Nutrition

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Potential Bioactive Components and Health

Promotional Benefits of Tea (Camellia sinensis)

Saptadip Samanta

To cite this article: Saptadip Samanta (2020): Potential Bioactive Components and Health
Promotional Benefits of Tea (Camellia�sinensis), Journal of the American College of Nutrition, DOI:
10.1080/07315724.2020.1827082

To link to this article: https://doi.org/10.1080/07315724.2020.1827082

Published online: 20 Nov 2020.

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JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
https://doi.org/10.1080/07315724.2020.1827082

REVIEW

Potential Bioactive Components and Health Promotional Benefits of Tea

(Camellia sinensis)
Saptadip Samanta
Department of Physiology, Midnapore College, Midnapore, West Bengal, India

ABSTRACT ARTICLE HISTORY

Tea is prepared from the young leaves, buds, stalks of the plant Camellia sinensis. The cultivation Received 9 August 2020
process of tea plants and the habit of tea drinking were initiated in China from ancient times. Accepted 16 September 2020
Now, the consumption of tea is very popular throughout the world and it is an integral part of
KEYWORDS
our social culture. Tea contains polyphenolic compounds (catechins and epicatechins), theaflavins,
Tea; Camellia sinensis;
flavonol glycosides, L-theanine, caffeine, theobromine, and volatile organic substances. These bio- epicatechins; theaflavins;
active components are responsible for the astringency, flavor, aroma, and taste of the tea as well theanine; health benefits
as its health beneficial effects. Moreover, tea has several medicinal values. The phytochemical com-
ponents are involved in the prevention and cure of many illnesses like cardiovascular diseases,
malignancy, digestive dysfunction, and metabolic disorders like obesity, diabetes. Tea flavonoids
show strong antioxidant properties. Caffeine and other methylxanthine regulate the intracellular
second messenger levels. Additionally, catechins exhibit anti-inflammatory effects. All these multi-
dimensional actions make some positive attributes in favor of neuroprotection, cardioprotection,
and cancer prevention. Various approaches are also taken to use tea ingredients as an adjuvant in
cancer therapy. This review emphasizes the importance of bioactive components, and their health
promotional activities.

Abbreviations: 5-FU: 5-Fluorouracil; 67LR: 5-HT: hydroxytryptamine/serotonin; 67-kDa: laminin

receptor; ACE: angiotensin-converting enzyme; AEDA: aroma extract dilution analysis; AGE:
advanced glycated end products; AMPA: a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid;
AMPK: adenosine 50 -monophosphate-activated protein kinase; ARE: antioxidant response elements;
AST: Aspartate aminotransferase; Bcl-2: B-cell lymphoma-2; BDNF: brain-derived neurotrophic fac-
tor; C: (þ)-catechin; cAMP: cyclic adenine monophosphate; CAT: catalase; CCL-5: CC chemokine lig-
and 5; CDK: cyclin-dependent kinase; CG: ()-catechin gallate; cGMP: cyclic guanosine
monophosphate; CK: creatinine kinase; CNS: central nervous system; COX: cycloxygenase; CREBP:
cAMP response element binding protein; CVD: cardiovascular diseases; CXCL-1: C-X-C motif chemo-
kine ligand 1; DBP: diastolic blood pressure; EC: ()-epicatechin; ECG: ()-epicatechin gallate; EEG:
electroencephalography; EGC: ()-epigallocatechin; EGCG: ()-epigallocatechin-3-gallate; EGF: epi-
dermal growth factor; eNOS: endothelial nitric oxide synthase; EPSFs: N-ethyl-pyrrolidinone substi-
tuted flavan-3-ols; Erk: extracellular regulated protein kinase; ET-1: endothelin-1; GABA: gamma-
aminobutyric acid; GC: ()-gallocatechin; GCG: ()-gallocatechin gallate; GC-O: gas chromatog-
raphy-olfactometry; GMP: guanosine monophosphate; GPx: glutathione peroxidise; GR: glutathione
reductase; GSH: reduced glutathaione; GSK3b: glycogen synthase kinase-3b; GST: glutathione s-
transferase; HbA1c: hemoglobin A1c; HDL: high-density lipoprotein; HO-1: heme oxygenase-1;
HPLC: high-performance liquid chromatography; IFN: interferon; IGF: insulin-like growth factor; IGF-
1: insulin-like growth factor-1; IGFB: IGF-binding protein; IL: interleukin; iNOS: inducible nitric oxide
synthase; IP3: inositol triphosphate; JNK: c-Jun N-terminal kinase; LC-MS: liquid chromatography
mass spectrometry; LDH: lactate dehydrogenase; LDL: low-density lipoprotein; LPO: lipid peroxida-
tion; LTP: long-term potentiation; MAPK: mitogen-activated protein kinase; MMP: Matrix metallo-
proteinases; NF-jB: nuclear factor-kappaB; NMDA: N-methyl-D-aspartate; NO: nitric oxide; Nrf2:
nuclear factor erythroid 2-related factor 2; OS: Oxidative stress; PDE: phosphodiesterase; PDGF:
platelet derived growth factor; PGI2: prostaglandin I2; PI3K: phosphatidylinositol-3-kinase; PPAR:
peroxisome proliferator activated receptor; PPO: polyphenol oxidase; SBP: systolic blood pressure;
SOD: superoxide dismutase; T2DM: type 2 diabetes mellitus; TF1: theaflavin; TF2A: theaflavin-3-gall-
ate; TF2B: theaflavin-30 -gallate; TF3: theaflavin-3,30 -digallate; TGF-b: transforming growth factor-b;
TLR: toll like receptor; TNF: tumor necrosis factor; VOCs: volatile organic compounds.

KEY TEACHING POINTS

 Origin and brief history of tea.
 Processing steps and characteristics of different types of teas.

CONTACT Saptadip Samanta saptadip174@gmail.com Department of Physiology, Midnapore College, Paschim Medinipur, Midnapore, West Bengal
721101, India
ß 2020 American College of Nutrition
2 S. SAMANTA
 Bioactive components of teas (green and black tea), their biochemical characteristics and health
promotional effects.
 Role of different bioactive components to control the various physiological and meta-
bolic disorders.
 Possibilities of use of tea component in cancer therapy.
Introduction
Tea is the second largest drink after water. It is widely con-
sumed as a beverage which is far ahead of coffee, beer,
wine, and carbonated soft drinks (1, 2). The journey of tea
was started from the past 2000 years ago. The credible
record of tea drinking from 3rd century AD was described
in the Chinese medical text. The benefits of tea drinking
were indicated by the ancient Chinese Physician Hua Tuo
who wrote “to drink bitter t’u constantly makes one think
better” (3). Gradually, tea consumption has been integrated
in our social culture. Now, the people have included this
practice in their daily life. Every day, 70% of the world’s
populations consume approximately 18–20 billion cups of
tea and to meet the market demand, about 2.9 billion tons
of tea is produced per year (4). The consumption of tea is
most popular in the Eastern part of the world and also in
different countries of Europe (5). However, drinking of cof-
fee is the fashionable choice in most of the Western world,
particularly in North and South America (6). Among the
different types of teas, green tea has greater acceptance
within the Chinese and Japanese people (7, 8). On the other
hand, black tea is popularly used by the Indian, European,
and American people (1, 5, 8).
Tea is made from the buds, delicate stalks, and upper
two leaves or some young leaves of the plant Camellia sinen-
sis (tea plant). This plant belongs to the family Theaceae.
Camellia sinensis was the native resident of Southeast Asia
(part of China India, and Burma/Myanmar). Another plant
Camellia sinensis var. assamica or Camellia assamica is also
used for the production of black tea. Based on the prepar-
ation technique, there are different types of teas; these
include black, green, white, yellow, oolong, pu-erh, and
others (9, 10). Green and white teas are non-fermented
products and considered as more valuable types. Preparation
of white tea is a sophisticated process, made from fresh
young leaves and buds. Tea contains as much as 30% soluble
ingredients, which may vary with the soil quality of the cul-
tivation area, climate conditions, genetic strain, geographical
region, shading, plucking season, position of the leaves as
well as the processing methods (11). Polyphenols are the
main constituents of tea that cover up to 20–35% of tea’s
dry weight. Among the polyphenols, catechins are the pre-
dominant group, comprising 60–80% of total polyphenols.
Catechin is 3,30 ,40 ,5,7-pentahydroxyflavan. The fresh bud
and the first two leaves of C. sinensis contain the highest
amount of ()-epigallocatechin-3-gallate (EGCG) which rep-
resents approximately 10% of dry weight, followed by
()-epicatechin gallate (ECG, 2.8%), ()-epigallocatechin
(EGC, 1.7%), and ()-epicatechin (EC, 0.8%) (12, 13).
Catechin, EC, and EGCG are the major flavonoids of green
tea (10, 14, 15). EGCG has several health beneficial proper-
ties such as anti-oxidant, anticancer, anti-obesity, antidia-
betic, and neuroprotective effects (16). However, black tea
contains much amount of theaflavin (TF) and its derivatives.
The average content of theaflavins is likely to be as follows:
theaflavin (18%), theaflavin-3-gallate (18%), theaflavin-30 -
gallate (20%), and theaflavin-3,30 -digallate (40%) (4).
Besides, a wide variety of other components like thearubi-
gins, theasinensins, L-theanine, methylxanthine, flavones,
phenolic acids, carbohydrates, alkaloids, and minerals are
also present in tea (Table 1) (4, 5).
The constituents of tea have a broad spectrum of health
benefits including antioxidant properties, protective against
various cancers, anti-inflammatory functions, anti-hyperten-
sive and cardio-protective actions, neuro-protection and
mental wellness, anti-diabetogenic properties, and effective
against hyperlipidemia, obesity, gastric dysfunctions, and
osteoporosis (10, 17, 18). Various studies had specifically
indicated the therapeutic properties of tea polyphenols. The
present review has focused on the bioactive components,
their properties, and health beneficial effects including mode
of action.
History of tea
Tea (Camellia sinensis) has a long history. This valuable
plant was originated in Southeast Asia, specifically around
the intersection of latitude 29 N and longitude 98 E near
the part of northeast India, north Burma, southwest China,
and Tibet. However, most of the records claimed that the
tea cultivation and drinking were started in Yunnan
Province during the Shang dynasty (1500 BC–1046 BC)
(19). Initially, it was used as a medicinal drink and also gave
pleasant feelings. Later, the use of tea was spread to Sichuan
where the people began to boil tea leaves for consumption
without adding any other components. Finally, it was estab-
lished as a stimulating drink irrespective of its medicinal
values (19).
According to Chinese mythology, Emperor Shen Nung of
the Han Dynasty discovered the tea in the year 2737 BC.
The people of the Tang dynasty initiated the processing of
tea. In this period tea was spread to Korea, Japan, and
Vietnam. The origin of modern delicate characteristics and
implication of tea within court society was started from the
Song Dynasty (960–1279). The modern practice of tea proc-
essing (roasting, pan-frying) as well as preparation of yellow
tea was introduced during the Ming dynasty at the time of
the mid-13th century (19–21). Until 18th century, tea manu-
facturing and trading were the monopolies of China. British

Table 1. The primary chemical components of green and black tea and their significant effects (52, 253–256).
Major compound
Polyphenols
Catechins and gallocatechin
Four major epicatechins and gallic acid
esters:
()-epicatechin (EC), ()-epicatechin gallate
(ECG), EGC, and ()-epigallocatechin
gallate (EGCG)
Theaflavins
(oxidized products of flavan-3-ols)
(TFs, thearubigin, and theabrownin)
Simple polyphenols
Other polyphenols
L-theanine (c-n-ethyl glutamine)
Amino acids
Caffeine
Other methylxanthines
theobromine and theophylline
(Bitter taste)
Plant are benefited as the components are
combatant against insects
Minerals
28 types of minerals are present.
(Potassium, calcium, magnesium, and
aluminum are the predominant (10 to 15%
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
% (wt/wt solids) in green tea % (wt/wt solids) in black tea
30–40%
30 9 
6 23
4 
2 3
6 23
3 3
3 3
3 3
<1 <1
5 5
3
Functional importance and probable mode
of action
 These plant metabolites give defense
against insects and other animals
Responsible for astringency
 Having antioxidant activities fi hydroxyl
groups exert antioxidant actions
 Increase lipid metabolism fi activates
AMP-mediated protein kinase
 Showing anti-diabetic and
insulinotropic effects
 Acting as antioxidants, scavenging ROS !
hydroxyl groups exert antioxidant effects
 Preserve the activity of
antioxidant enzymes
 Hypotensive effect fi increase
NO synthesis
 Enhancing beta-oxidation and energy
expenditure
 Protective against diabetes fi induce
postprandial insulin secretion, inhibition of
a-amylase and a-glucosidase
 Inhibitory activity against angiotensin-
converting enzyme (ACE) fi regulate
blood pressure
 Stimulate the sympathetic nervous system
by inhibiting noradrenaline degradation
All these products contribute to the color
and quality of black tea
 Acting as strong antioxidant
 Inhibit lipase activity
 Decrease LDL oxidation
 Showing anti-inflammatory properties fi
decrease leukotriene B4 (LTB4), and plasma
P-selectin activity
 Prevent apoptosis fi reduce endoplasmic
reticulum (ER) stress
 Inhibit plasminogen activator inhibitor type
1 (PAI-1) fi initiate of fibrinolysis
 Anti-diabetogenic activity fi inhibit
a-glucosidase and maltase
 Increase energy expenditure fi induce the
expression of uncoupler protein (UCP)-1
and peroxisome proliferator-activated
receptor-gamma coactivator-1a (PGC-1c) in
brown adipose tissue
 Inhibit fatty acid synthase fi reduce lipid
accumulation
 Promote acetylcholine (ACh)-induced
endothelium-dependent relaxations
 Acting as antioxidant fi decrease ROS
 Similar type functions of catechins and
epicatechins
 Responsible for umami taste
 Promote alpha brain wave activity
 Increase 5-HT levels at the peripheral
nerve endings fi hypotensive activity
 Give brothiness of tea
 Increase the taste and aroma of the tea fi
stimulate taste receptor
 Relaxation of smooth muscles and
maintenance of cardiac activity fi inhibits
phosphodiesterase, increases intracellular
cAMP levels and NO synthesis
 Theobromine increases HDL-cholesterol
levels and reduces LDL concentration
 Relaxation of smooth muscle fi increase
eNOS, NO synthesis
 High amount of fluoride helps to prevent
tooth decay in humans.
 Some minerals enhance antioxidant activity
(continued)
4 S. SAMANTA

Table 1. Continued.
Major compound
w/w).
Tea leaves have higher than average
amount of fluorine, manganese, arsenic,
nickel, selenium, and iodine)
Enzymes
Polyphenol oxidase (EC 1.14.18.1 and EC
1.10.3.2); peroxidase (EC 1.11.1.7)
Pigments
(chlorophylls and carotenoids)
Volatile compounds
(linalool, linalool oxide, geraniol,
phenylacetaldehyde nerolidol,
benzaldehyde, methyl salicylate, phenyl
ethanol, and trans-2-hexenal, n-hexanal, cis-
3-hexenol, and b-ionone)
% (wt/wt solids) in green tea
Functional importance and probable mode
% (wt/wt solids) in black tea of action
 They are responsible for the enzymatic
oxidation of polyphenols and browning of
tea leaves during black tea production
 Chlorophylls are oxidized to black
pigments, pheophytins which give a dark
color of finished tea.
 Tea carotenoids and xanthophylls are
responsible for the orange and yellow
color of finished tea leaves
 The volatile substances in tea leaves are
largely responsible for tea’s flavor
and aroma
 Linalool and linalool oxide are responsible
for sweetness
 Geraniol and phenylacetaldehyde give
floral aroma
 Nerolidol, benzaldehyde, methyl salicylate,
and phenyl ethanol generate fruity flavor
 Trans-2-hexenal, n-hexanal, cis-3-hexenol,
and b-ionone make a tea’s fresh flavor

traders had started business on tea in China after first
opium war (19).
Buddhist monks brought the tea in Japan during 589–618
AD at the time of the Sui Dynasty. The application of green
tea or Japanese sencha was popularized under the leadership
of the Buddhist priesthood. The Goryeo Dynasty (918–1392)
and the Joseon Dynasty (1392–1910) of Korea had popular-
ized the tea in Korean society. It is assumed that the
Portuguese travelers and sailors brought the tea in Europe
near the period of 1516. In the early 17th century, the
Dutch East India Company carried the tea to Amsterdam
from China. The first selling of tea was started in London in
1657 by Thomas Garway. In the year 1750, tea became the
British national drink. The use of tea in Australia was initi-
ated after the British colonization (20–23).
British East India Company had started commercial tea
plantation in Darjeeling and Assam of India, Burma, and Sri
Lanka from 1824. Several companies (Lipton, Tetley,
Typhoo, and others) had taken land as loan for the develop-
ment of tea gardens. Since 1836, the British people intro-
duced tea culture in India. After the independence of India,
the Indian Tea Board successfully increased the tea cultiva-
tion. Now, India is the highest consumer of tea in the world.
Despite China and India, other countries like Kenya, Sri
Lanka, Iran are holding the position in the global scenario
of tea production (3, 21, 24).
Types of tea
There are five true teas: (1) black tea, (2) green tea, (3)
oolong tea, (4) pu-erh tea, and (5) white tea. All true teas are
prepared from the leaves of the Camellia sinensis plant. The
classifications of these teas depend on the preparation and
processing of tea leaves. The tea processing has five basic
steps—plucking, withering, rolling, oxidizing, and drying.
Black tea
Black tea is the most popular drink in the world. It is mostly
oxidized product among all types of teas. It has slightly bitter
and astringent taste, stronger flavor and contains more caffeine
than other teas. Many people enjoy the drink together with a
small amount of sugar milk. There are a few differences
between green and black tea. Black tea requires longer process-
ing steps. Consumption of black tea can reduce blood pressure,
risk of type 2 diabetes, and improve the cholesterol profile
(25–27). The polyphenolic constituents of black tea (theaflavins
and thearubigins) provide several health benefits against obes-
ity, diabetes, cancer, atherosclerosis, inflammatory diseases, and
osteoporosis (28).
Green tea
Green tea is very popular in China for millennia. There are
many varieties of green tea; the more popular kinds include
sencha, genmaicha, and matcha. To make green tea, the oxi-
dation process is completely left out that gives the light,
fresh flavor, and delicate color. Green tea is very healthy, as
it contains large amounts of antioxidants (29) which can
neutralize the free radicals in the body. Regular consump-
tion of green tea can reduce the risk of cancer, blood pres-
sure, insulin resistance diabetes, and increase glycemic
control (30–32).
Green tea contains polyphenols (90%), amino acids
(7%), theanine, proanthocyanidins, and caffeine (3%). It
is the highest source catechin which exerts the major benefi-
cial effects. Varieties of flavonols (myricetin, kaempferol
quercetin, chlorogenic acid, coumarylquinic acid, and theo-
gallin) are also the constituent of green tea (33). The content
of theanine, theobromine, caffeine, catechin, and gallocate-
chin gallate vary with the age of leaf and the harvesting
time. Younger leaves carry a greater amount of caffeine,

EGCG, ECG, and other catechins as compare to older leaves
(33, 34). Among the catechins, EGCG comprises 60–65% in
green tea (35).
Oolong tea
Oolong tea has some similarities with black tea and has
fresh color. The taste is naturally sweet with flowery, fruity,
or smoky aroma. The initial processing is very similar to
black tea; but, the tea is partially oxidized as the oxidation is
stopped by heating. Oolong tea contains a range of polyphe-
nols found in both black tea and green tea. It can reduce
blood glucose levels and improve the cholesterol profile
(36, 37).
Pu-erh tea
Pu-erh tea is a fermented tea drink, contains lots of benefi-
cial bacteria that act as probiotics. It is made through an
additional step of post-fermentation. This step increases the
amount of gallic acid and decreases flavan-3-ols (38), and
theanine (39) content. During the processing, microbial fer-
mentation is done. Normally, the taste of pu-erh tea is bit-
terer than standard tea, but it becomes milder over time.
Pu-erh tea can improve health markers in patients with
metabolic syndromes (40, 41).
White tea
White tea is the mildest tea in taste as compared with black
tea. It contains 25% of the caffeine in comparison to coffee
and also useful for individuals who have caffeine sensitiv-
ities. It is prepared only from the unopened buds and fresh
young leaves which are allowed to oxidize naturally. Its
name comes from the fine silvery-white hairs on the
unopened buds, which gives the plant a whitish appearance.
The least processing is required concerning to all tea types,
but the polyphenolic components are similar to green
tea (42).
Tea processing
The production of any type of tea is started after pluck-
ing of green tea leaves; later, the process is diversified
for the production of specific kinds of tea. Fresh tea
leaves are fully hydrated, rich with astringent and bitter
compounds, and devoid of aroma (43). The characteristics
of the fresh tea leaves are different from processed tea.
The tea leaves are passed through the several steps of
processing like withering, fixation, rolling, fermentation,
and drying (44).
Tea plant and plucking of leaves
Production of tea initiates with the plantation of Camellia
sinensis (tea plants). The practice of tea plant cultivation is
now being spread over the 45 countries throughout the
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 5
world. The tropical and subtropical climate and slightly
acidic soil make a good environment for the cultivation of
tea plants (4, 45). There are some morphological differen-
ces between the Assamese and Chinese varieties of the tea
plants, but the cluster analysis of chromosome and hybrid-
ization study had revealed that Camellia sinensis was origi-
nated in a particular area specifically in the northern part
of Burma and Yunnan province of China. Thus, it is sug-
gested that C. assamica is the variant of C. sinensis. The
variation in the plants may be due to the generation of
intermediate hybrids and spontaneous polyploids (46). The
genome sequence and the molecular basis of biosynthesis
of tea components were also established (47, 48). The
green leaves are collected regularly at intervals ranging
from 5 to 8 days. The plucking of the soft two leaves and
the buds are generally completed by the well-trained
individuals.
Withering
Tea leaves are thick and waxy. They must be softened, or
withered, make them pliable for crafting. Withering is the
process of reduction of moisture from the leaves, the water
content of the leaves reaches to about 60  70%. Withering
preserves the PPO enzyme. As the withering occurs in nor-
mal temperatures, most of the VOCs remain stable (13).
Withering starts the oxidation of epicatechins and the pro-
duction of TFs (49). The increase of withering time elevates
gallic acid content (50).
Rolling or bruising
Rolling is necessary for curling and twisting of the tea
leaves. This process disrupts the surface of the fresh tea
leaves, breaks the cell walls, and facilitates the release of pol-
yphenols and the enzyme polyphenol oxidase (PPO) that
initiates the oxidation step followed by formation of TFs
(49). Oolong tea, black tea, and pu-erh tea require a min-
imum stage of the rolling process as compared with green
tea and white tea.
Oxidation
Oxidation (fermentation) is a vital step for the preparation
of different kinds of teas. Black tea is a fully oxidized prod-
uct; while, oolong tea is a partially oxidized substance. The
temperature and time requirements for complete oxidation
are about 26  C and 30 minute to 2 hours, respectively. The
step of oxidation is fully avoided in green tea preparation;
therefore, unoxidized leaves remain green in color. Tea
leaves contain polyphenol oxidase (PPO) and peroxidase
(POD). They are responsible for the enzymatic browning of
tea leaves. As the cell walls have been broken during rolling,
cutting, or crushing, the intracellular enzymes appear out-
side the cells and promote the level of oxidation of polyphe-
nols in the presence of air. These enzymes may be
denatured or deactivated through heat treatment during fix-
ing so that further browning cannot occur. PPO preferred
6 S. SAMANTA
the gallocatechin, epigallocatechin, and epigallocatechin gall-
ate for the oxidation coupling reactions. There are two types
of PPO: (1) monophenol monooxygenase or tyrosinase
(EC1.14.18.1) and (2) O-diphenol: O2 oxidoreductase
(EC1.10.3.2). Another enzyme POD is less active as the indi-
genous catalase eliminates peroxide before involvement in
reaction. O-quinone of catechin dimers and theasinensins
are synthesized during rolling and fermentation steps.
However, oxidation in low temperature increases TFs, while
slightly higher temperatures (30  C) increases thearubigins
levels (13, 49, 51–53).
Fixing
To stop the oxidation process, the tea leaves are heated to
denature the enzymes responsible for oxidation and stops
the continuous browning of the leaves. This step is applic-
able for all types of teas except black tea where oxidation
slowly halts during the final drying step.
Roasting temperature is the critical factor for the vari-
ation in components. High temperature degrades the ori-
ginal compounds and increases the appearance of a new
stable compound which determines the aroma, and taste of
the final tea. The amount of flavoring agent 2,5-dimethyl
pyrazine increased during the roasting (54). Heat treatment
converts the L-theanine to D-theanine (55). However, Mao
et al. (56) reported that the roasting step declined overall
theanine content. Similarly, cis-catechins are converted to
more stable trans-catechins (GC, CG) (57). The concentra-
tion of ()-epicatechin levels was also decreased in this step
(55, 58). Moreover, high temperature promotes the forma-
tion of EGCG dimmers (theasinensins) from EGCG (59)
and influences the nucleophilic activity of catechins to gen-
erate catechin–carbonyl and catechin–theanine conjugate
products (60).
Drying
All teas must be dried to remove residual moisture at the
final stage of preparation. The average moisture content
varies within 3% to 5% (61). It is essential for long-term
storage. Finished teas are very hygroscopic and rapidly
absorb moisture. They are packed either in plywood tea
chests or multi-walled aluminum craft paper for
distribution.
Bioactive components of tea
Tea chemistry is very complex. Tea leaves contain thousands
of chemical compounds that are responsible for the flavor
and aroma of teas. During processing, these compounds are
converted to more complex components that determine the
quality of the teas. The aroma of tea is provided by several
volatile compounds (“aroma complex”) of the tea liquor.
Numerous nonvolatile compounds are present in the tea
infusion; among them, some are water-soluble, but, solubil-
ity depends on temperature, total dissolve solids, pH, etc.
Tea leaves contain polyphenols (flavonoids), amino acids,
enzymes, pigments, carbohydrates, alkaloids, methylxan-
thines, vitamins, minerals, enzymes, and many volatile
aromatic compounds (Table 1) which give desirable appear-
ance, aroma, flavor, and taste of the teas.
Tea polyphenols
Chemically flavonoids are 2-phenyl benzopyran-based com-
pound. They are subdivided into six classes such as flavones,
flavanones, isoflavones, flavonols, flavanols, and anthocya-
nins. Among these flavanols (flavan-3-ols) and flavonols are
the major important polyphenols in tea which account for
25–35% of the dry weight of fresh leaves (13, 52, 62, 63).
They principally act as antioxidants, scavenge reactive oxy-
gen species (ROS) and reactive carbonyl species (RCS), and
exert health beneficial effects. Tea also contains gallic acid
which is chemically hydroxybenzoic acid.
Catechins (flavan-3-ols) are the common tea flavanols
(64). Structurally it has two benzene rings (A and B) and a
C-ring (dihydropyran heterocycle) which bears a hydroxyl
group on carbon 3 (18). A-ring and B-ring are linked by the
three-carbon atom heterocyclic C ring. A-ring and B-ring
have close similarities with resorcinol moiety and catechol
moiety, respectively. A-ring contains hydroxyl groups at the
5 and 7 positions. B-ring carries hydroxyl groups either in
30 and 40 carbon (ortho-30 40 dihydroxyl group) or in 30 , 40 ,
and 50 carbon (30 40 50 trihydroxy group). The presence of
hydroxyl groups in the different locations and a double
bond between carbon atoms 2 and 3 in the C ring are the
basis of subclasses of flavanones, flavonols, flavones, isofla-
vones, anthocyanidins, and flavan-3-ols. A gallate group is
attached at position 3 of the C-ring to form catechin gallate
(3, 14). Catechins (C) give two trans and two cis isomers
due to the presence of two chiral centers on carbons 2 and
3, respectively. Epicatechins belong to cis configuration.
There are varieties of catechins and its gallic acid esters in
tea; these include ()-epicatechin (EC), ()-epicatechin gall-
ate (ECG), gallocatechin (GC), ()-epigallocatechin (EGC),
and ()-epigallocatechin gallate (EGCG) (14, 15, 65). About
80% of the total catechins belong to EGCG, ECG, and
EGC (34).
All the catechins are colorless, water-soluble compounds,
responsible for bitter taste and astringency. Green tea is the
major source of these polyphenols (15). Kaneko et al. (66)
reported that gallic acid and theogallin (1-galloylquinic acid)
were also present in green tea. Moreover, different
derivatives of quinic acids like 3-galloyl, 4-galloylquinic acid,
1,3,5-trigalloylquinic acid, 4-(digalloyl) quinic acid, 5-(digal-
loyl)quinic acid, and either 3-galloyl-5-(digalloyl)quinic acid
or 3-(digalloyl)-5-galloylquinic acid were also the constituent
of green tea (67).
The gallic acid ester of catechin is poorly absorbed in the
intestine. The plasma concentration of 40 -O-methyl-epigallo-
catechin is 5 times higher than the concentration of epigal-
locatechin (68). Glucuronidation or sulfate conjugation with
epicatechin produced different components (epicatechin-30 -
O-glucuronide, 40 -O-methylepicatechin-30 -O-glucuronide, 40 -
O-methyl-epicatechin-5- or 7-O-glucuronide, 40 -O-

methylepicatechine, and epicatechin aglycone) (69, 70).
Besides flavanols, flavonols, flavones, and isoflavones, antho-
cyanins are also present in tea leaves which contribute to
the color and taste of tea.
Apigenin is a specific type of flavonoid exhibits chemo-
preventive properties. It is recognized as an anti-prolifera-
tive, anti-inflammatory, and anti-metastatic agent. This
flavonoid can induce caspase-dependent-apoptosis in leuke-
mia cells by activating protein kinase delta (PKC-d) (71).
Balasubramanian et al. (72) had studied the effects of apige-
nin as a chemotherapeutic agent. They reported that apige-
nin downregulated the expression of keratinocyte
differentiation factor involucrin (hINV). At the functional
level, hINV activates PKC-d, Ras, MEKK1, and MEK3 cas-
cade followed by activation of the AP1 factor and its bind-
ing to DNA elements. Apigenin inhibits AP1 expression and
its binding to the hINV promoter. Another report by
Horinaka et al. (73) indicated that apigenin upregulated the
death receptor 5 (DR5) as well as the activity of tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL) to
modulate the apoptosis in malignant cells.
Theaflavins (TFs), thearubigins, and theabrownin
Green tea and black tea contain different types of flavonoids.
The monomeric flavanols are poorly present in black tea.
They are easily converted to dimeric theaflavins or poly-
meric thearubigins after oxidation. The chemical compo-
nents of black tea are mostly oxidized products of
polyphenolic compounds. Two enzymes polyphenol oxidase
and peroxidase are involved in this process. They convert
the flavanols to pyrogallol and catechol. Further oxidation of
polyphenols produces theaflavins and thearubigins. Black tea
contains four types of theaflavins; these include theaflavin
(TF1), theaflavin-3-gallate (TF2a), theaflavin-30 -gallate
(TF2b), and theaflavin-3,30 -digallate (TF3). Initially, it was
considered that theaflavin is the coupling oxidation product
of EGC and EGCG, but later study indicated that the cou-
pling oxidation reaction between EC and EGC produced
theaflavin (TF1) (74). Other types of theaflavins TF2a
(EC þ EGCG), TF2b (ECG þ EGC), and TF3
(ECG þ EGCG) are also the products of the coupling oxida-
tion reaction of different epicatechins (28). Theaflavins are
responsible for the bright orange-red color of tea and give
astringency (75). Other phenolic pigments like epitheaflavic
acid, epitheaflavic acid gallate, and isotheaflavin are also
observed in back tea. They form during the coupling reac-
tion with the EC and gallic acid, ECG and gallic acid, and
EGC and catechin, respectively (52, 74). Another pigment
thearubigin is soluble in hot water. It is the profound oxi-
dized product of theaflavins and catechins. Berkowitz et al.
(76) revealed that the EC’s product epitheaflavic acid and
gallic acid were involved in the reaction of thearubigins syn-
thesis. Theabrownin is formed at the post-fermentation
period of pu-erh tea. Another component theasinensin is a
colorless catechin dimmer (bisflavanol) which is a dimeric
product of gallocatechin-gallocatechin (77).
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 7
Flavonol glycosides
The water-soluble flavonol glycosides make up 2–3% of sol-
ids of tea (52). Different compounds like quercetin, kaemp-
ferol, myricetin, and their glycosides belong to the family
flavonol glycosides which bears 4-oxo and 3-hydroxy group
in the C ring. Kaempferol-3-O-glucosyl-(1-3)-rhamnosyl-(1-
6)-galactoside, quercetin-3-O-glucosyl-(1-3)-rhmnosyl-(1-6)-
glucoside, and quercetin-3-O-glucosyl-(1-3)-rhamnosyl-(1-
6)-galactoside are commonly present in the tea leaves (78).
Amino acid L-theanine
The tea leaves contain non-protein amino acid L-theanine.
The average amount of this amino acid is 3 to 5 mg/g of
fresh weight. Theanine is L-c-glutamyl ethylamide. This
amino acid is synthesized in roots and deposited in leaves
(79). At the physiological level theanine binds with AMPA
(a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid),
kainite, and NMDA (N-methyl-D-aspartic acid) receptors
(80, 81). It exerts an antagonistic effect for AMPA and kai-
nate receptors (82), but acts as an agonist for the NMDA
receptor (83). Theanine is responsible to elicit umami taste
which is unique than the other four primary tastes (salt,
sour, sweet, and bitter). This amino acid stimulates the
T1R1 þ T1R3 heterodimer umami taste receptor. The activa-
tion of T1R1 þ T1R3 expressing cells enhances taste
response (84). Thus, L-theanine improves the taste and qual-
ity of the tea.
Hydrolyzable tannins
Tannin belongs to phenolic acid components. These phen-
olic acids form a conjugate with one molecule of glycosyl
residue to generate hydrolyzable tannins (85). The major
hydrolyzable tannins of tea leaves are hydroxybenzoic acids,
hydroxycinnamic acids, quinic acid, galloylquninic acid, and
caffeoylquinic acid (86). Hydrolysis of these tannins produ-
ces phenolic acids. These compounds are highly soluble in
water and available in tea infusion. They are responsible for
the dark color and robust flavors.
Caffeine and theobromine (methylxanthine)
Tea contains 3% of caffeine. Chemically caffeine is the
1,3,7-trimethylxanthine; whereas, theobromine is the 3,7-
dimethylxanthine. Both of these compounds show an excit-
ing response in the body. Another methylxanthine theacrine
is an acidic compound (1,3,7,9-tetramethyluric acid). The
metabolic products of caffeine are paraxanthine and theo-
phylline. All these are collectively known as methylxanthine.
Caffeine is the antagonist of the GABA receptor that has a
protective role against Alzheimer’s and Parkinson’s disease
(87). Theobromine is the adenosine receptor antagonist and
potentiates the neurotransmitter release leading to stimula-
tory effects. Caffeine also elicits adenosine receptor antagon-
istic effects. Consumption of caffeine or theobromine
modulates the activity of the adenosine A1 receptor of
8 S. SAMANTA

Table 2. The chemical structure, general properties, and physiological importance including fundamental basis of mode of action of tea components.
Compounds Property Physiological importance
Flavan skeleton: A and B are the two benzene  MF: C15H14O  It is the fundamental structure of tea
rings and C-ring is the dihydropyran heterocycle  MW: 210.27g/mol polyphenols, the major bioactive
ring  IUPAC Name: 2-phenyl-3,4-dihydro- compounds and responsible factor for
2H-chromene many physiological actions
 Flavan is a chromane (a benzopyran
-a benzene ring ortho-fused across
positions 2 and 3 of a pyran ring)
substituted by a phenyl group at
position 2

Flavone (Apigenin)  MF: C15H10O5  Inducing autophagy in leukemia cells

 MW: 270.24g/mol  Acting as an antineoplastic agent
 IUPAC Name: 5,7-dihydroxy-2-(4-
hydroxyphenyl)chromen-4-one
 It is a trihydroxyflavone that
contains hydroxy groups at positions 40 ,
5 and 7

Gallic acid  MF: C7H6O5  Acting as astringent

 MW: 170.12g/mol  Inhibiting cyclooxygenase 2
 IUPAC Name: 3,4,5-  Showing antioxidant activity
trihydroxybenzoic acid  Having antineoplastic property
 It is the conjugate acid of a gallate  Inhibiting arachidonate 15-lipoxygenase
 Inducing apoptosis

Catechins  Catechins  Exhibiting anti-inflammatory activity

 MF: C15H14O6  Showing powerful antioxidant activity
 MW: 290.27g/mol  Regulate inflammatory response
 IUPAC Name: (2R,3S)-2-(3,4-  Exerting cytoprotective effects
dihydroxyphenyl)-3,4-dihydro-2H-  Treating agent for osteoarthritis
chromene-3,5,7-triol
 Catechin is a tannin peculiar to green
and white tea
 GC
 MF: C15H14O7
 MW: 306.27g/mol
 IUPAC Name: (2R,3S)-2-(3,4,5-
trihydroxyphenyl)-3,4-dihydro-2H-
chromene-3,5,7-triol
 It contains another hydroxyl group at
positions 40 (the trans isomer)
 CG
 MF: C22H18O10
 MW: 442.4g/mol
 IUPAC Name: ((2S,3R)-2-(3,4-
dihydroxyphenyl)-5,7-dihydroxy-3,4-
dihydro-2H-chromen-3-yl) 3,4,5-
trihydroxybenzoate
 It is an enantiomer of a (þ)-catechin-3-
O-gallate.
 Chemically it is a gallate ester obtained
(þ)-catechin by formal condensation of the carboxy
group of gallic acid with the (3 R)-
hydroxy group of ()-catechin
 GCG
 MF: C22H18O11
 MW: 458.4g/mol
 IUPAC Name: ((2S,3R)-5,7-dihydroxy-2-
(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-
chromen-3-yl) 3,4,5-trihydroxybenzoate
 It is a 3,4,5-trihydroxybenzoic acid

()-gallocatechin
(continued)

Table 2. Continued.
Compounds
(þ)-catechin gallate
()-gallocatechin gallate
()-Epicatechin (EC),
()-Epicatechin gallate (ECG)
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 9
Property Physiological importance
 MF: C15H14O6  Having strong antioxidant property
 MW: 290.27g/mol  Involve in cardioprotective and cancer-
 IUPAC Name: (2R,3R)-2-(3,4- protective activity
dihydroxyphenyl)-3,4-dihydro-2H-  Used as an adjuvant in chemotherapy
chromene-3,5,7-triol
 ()-epicatechin is a catechin with
(2 R,3R)-configuration. It is an
enantiomer of a (þ)-epicatechin
 MF: C22H18O10
 MW: 442.4g/mol
 IUPAC Name: (2-(3,4-dihydroxyphenyl)-
5,7-dihydroxy-3,4-dihydro-2H-chromen-3-
yl) 3,4,5-trihydroxybenzoate
(continued)
10 S. SAMANTA
Table 2. Continued.
Compounds Property
()-Epigallocatechin (EGC)  MF: C15H14O7
 MW: 306.27g/mol
 IUPAC Name: (2R,3R)-2-(3,4,5-
trihydroxyphenyl)-3,4-dihydro-2H-
chromene-3,5,7-triol
 ()-epigallocatechin is a flavan-
3,30 ,40 ,5,50 ,7-hexol having (2 R,3R)-
configuration. It is an enantiomer of a
(þ)-epigallocatechin
()-Epigallocatechin gallate (EGCG)  MF: C22H18O11
 MW: 458.4g/mol
 IUPAC Name: ((2R,3R)-5,7-dihydroxy-2-
(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-
chromen-3-yl) 3,4,5-trihydroxybenzoate
Theaflavins (TFs)  MF: C29H24O12
 MW: 564.5g/mol
 IUPAC Name: 3,4,6-trihydroxy-1,8-
bis((2R,3R)-3,5,7-trihydroxy-3,4-dihydro-
2H-chromen-2-yl)benzo(7)annulen-5-one
 It is a biflavonoid commonly present in
black tea in maximum concentrations.
 The positions 1 and 8 of 3,4,5-
trihydroxybenzocyclohepten-6-one is
linked with (2 R,3R)-3,5,7-trihydroxy-3,4-
dihydro-2H-chromen-2-yl groups
Thearubigins  MF: C43H34O22
 MW: 902.7g/mol
 IUPAC Name: 7-(2-carboxy-1-((2R,3R)-5,7-
dihydroxy-3-(3,4,5-trihydroxybenzoyl)oxy-
3,4-dihydro-2H-chromen-2-yl)ethyl)-5-
((2R,3R)-5,7-dihydroxy-3-(3,4,5-
trihydroxybenzoyl)oxy-3,4-dihydro-2H-
chromen-2-yl)-2-hydroxy-3-
oxocyclohepta-1,4,6-triene-1-
carboxylic acid
Caffeine  MF: C8H10N4O2
 MW: 194.19g/mol
 IUPAC Name: 1,3,7-trimethylpurine-
2,6-dione
 Caffeine is a purine alkaloid that occurs
naturally in tea and coffee.
 It is a trimethylxanthine, methyl groups
are located at positions 1, 3, and 7
Physiological importance
 Inhibiting cellular oxidation and
preventing free radical-mediated damage
 Showing potential
chemopreventive property
 Acting as an anti-obesity agent
 Having antimutagenic property- prevent
spontaneous or induced mutations
 Acting as a neuroprotective agent -
prevent damage to the brain cells or
spinal cord from ischemia, stroke
 Having potent antioxidant properties
-neutralizes free-radical species
 Increasing the activity of detoxifying
phase II enzymes in the liver.
 Exhibiting antitumor effects -inducing
tumor cell apoptosis
 Arresting cell division
 Inhibiting cancer cell invasion
 Blocking growth factor-induced
angiogenesis
 Acting as cardio-protective agent
 Protective against oxidative damage of
DNA and protein
 Decrease LDL oxidation
 Prevent osteoporosis
 Structurally related to adenosine
 Adenosine receptor antagonist at CNS
 Psychotropic agent
 Promoting neurotransmitter release
in CNS
 Stimulating the activity of the medullary,
vagal, vasomotor, and respiratory centers
in the brain
 Acting as a ryanodine receptor agonist
(continued)
 JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 11

Table 2. Continued.
Compounds Property Physiological importance
 Inhibiting phosphoric diester hydrolase
(non-specific serine/threonine protein
kinase inhibitor)
 Having anti-inflammatory activities
Theobromine  MF: C7H8N4O2  Acting as vasodilator and
 MW: 180.16g/mol bronchodilator agent
 IUPAC Name: 3,7-dimethylpurine-  Stimulant of smooth muscle
2,6-dione  Having diuretic activity
 A dimethylxanthine (purine alkaloid),  Adenosine receptor antagonist
methyl groups at the positions 3 and 7  Anti-hypertensive agent
 Stimulant for the medullary, vagal,
vasomotor, and respiratory centers
 Promoting bradycardia
 Inhibiting phosphodiester hydrolase-
increase intracellular cAMP levels
Theophyline  MF: C7H8N4O2  Inhibiting phosphodiesterase and
 MW: 180.16g/mol prostaglandin production
 IUPAC Name: 1,3-dimethyl-7H-purine-  Maintain calcium flux and
2,6-dione intracellular calcium distribution
 It is a xanthine derivative (structurally  Antagonize adenosine receptor action
similar to caffeine)-  Relax bronchial smooth muscle
dimethylxanthine having methyl groups  Having a vasodilation effect
at 1 and 3 position  Stimulating effects in the CNS,
cardiac muscle
 Inducing diuresis
 Influencing gastric acid secretion
 Anti-inflammatory and
immunomodulatory activity
L-Theanine  MF: C7H14N2O3  Neuroprotective agent
 MW: 174.2g/mol  Reducing tiredness
 IUPAC Name: (2S)-2-amino-5-  Improve cognitive functions
(ethylamino)-5-oxopentanoic acid
 Theanine (non-protein amino acid ) is a
precursor of ethylamine
 It is a N(5)-alkylglutamine where the
alkyl group is ethyl; alternatively, it is a
tautomer of an N(5)-ethyl-L-glutamine
Linalool  MF: C10H18O  It gives fragrance
 MW: 154.25 g/mol  Having analgesic anti-inflammatory, anti-
 IUPAC name: 3,7-dimethylocta-1,6-dien- carcinogenic effects
3-ol
 Linalool is tertiary alcohol and a
monoterpenoid
 It is an octa-1-6diene substituted by
methyl groups at positions 3 and 7 and
a hydroxy group at position 3

Geraniol  MF: C10H18O  Functioning as fragrance

 MW: 154.25g/mol  Exhibiting anti-inflammatory, antioxidant,
 IUPAC Name: (2E)-3,7-dimethylocta-2,6- anti-cancer, and neuroprotective activity
dien-1-ol  Sensitize the tumor cells to
 Geraniol is a volatile oil component chemotherapeutic agents
 It is a monoterpenoid, consisting of two
prenyl units linked head-to-tail
 Functional site is the hydroxy group at
its tail
Phenylacetaldehyde  MF: C8H8O  It is an aroma active compound
 MW: 120.15g/mol  It has toxicity, but metabolized to
 IUPAC Name: 2-phenylacetaldehyde phenylacetic acid and excreted
 Phenylacetaldehyde is an oxidation- through urine
related aldehyde

(continued)
12 S. SAMANTA

Table 2. Continued.
Compounds Property Physiological importance
Nerolidol  MF: C15H26O  Flavoring agents
 MW: 222.37g/mol  Decreasing oxidative stress and maintain
 IUPAC Name: (6E)-3,7,11- the activity of SOD CAT
trimethyldodeca-1,6,10-trien-3-ol

Benzaldehyde  MF: C7H6O  Flavoring component

 MW: 106.12g/mol  Having oncostatic properties
 IUPAC Name: benzaldehyde
 It is an aromatic aldehyde having a
single formyl group

Methyl salicylate  MF: C8H8O3  Coloring and flavoring agent

 MW: 152.15g/mol
 IUPAC Name: methyl 2-hydroxybenzoate
 It is a benzoate ester -the methyl ester
of salicylic acid
 Pharmacologically similar to aspirin and
other NSAIDs
 Having analgesic activity
 Cyclooxygenase inhibitor- preventing
prostaglandin and thromboxane
A2 synthesis

Trans-2-hexenal  MF: C6H10O  Flavoring agent

 MW: 98.14g/mol
 IUPAC Name: (E)-hex-2-enal
 The olefinic double bond of the
molecule gives E configuration

n-Hexanal  MF: C6H12O  Significantly inhibit gap-junctional

 MW: 100.16g/mol mediated intercellular
 IUPAC Name: hexanal communication (GJIC),
 It is an alkyl aldehyde, a saturated fatty  Preventing electrical injury of cardiac
(medium-chain) aldehyde myocytes, brain cells,
 Inhibiting the growth of cancer cells
Cis-3-hexenol  MF: C6H12O  Treating as an aroma compound
 MW: 100.16g/mol  Flavoring agent
 IUPAC Name: (Z)-hex-3-en-1-ol
 It is known as (Z)-3-hexen-1-ol and
leaf alcohol
 This primary alcohol consists of (3Z)-hex-
3-ene substituted by a hydroxy group at
position 1
b-Ionone  MF: C13H20O  Acting as flavoring and fragrance agent
 MW: 192.3g/mol  Having antioxidant activity
 IUPAC Name: (E)-4-(2,6,6-
trimethylcyclohexen-1-yl)but-3-en-2-one
 This ionone is but-3-en-2-
one substituted by a 2,6,6-
trimethylcyclohex-1-en-1-yl group at
position 4
 b-ionone is an end ring analog of
b-carotenoid, a cyclic isoprenoid
 It is the part of essential oils

MF: Molecular formula; MW: Molecular weight.


cardiac muscle and increases the cardiac activity by acceler-
ating the heart rate.
Tea leaves also contain a less amount of another dime-
thylxanthine theophylline. It is an antagonist of adenosine
receptors, competitively inhibits PGE (type III and IV). The
result is high levels of intracellular cAMP in smooth muscle
cells of airways resulting in bronchodilation and anti-inflam-
matory response (reduction of neutrophil chemoattractant
cytokine IL-8). cAMP induces the expression of cAMP-
dependent protein phosphatase leading to inactivation of
mitogen-activated protein kinase phosphatase 1 (MKP-1)
and repression of cytokine production (88). Theophylline
influenced the length and complexity of the dendritic pro-
cess in melanocytes. This methylxanthine inhibited phospho-
diesterase to elevate cAMP levels and melanogenesis. Cell
culture (B16F10 murine melanoma cells) study had revealed
that theophylline-induced melanogenesis was mediated by
mitogen-activated protein kinase kinase 1/2 (MEK 1/2) and
Wnt/b-catenin signaling that upregulated the expression of
microphthalmia-associated transcription factor (MITF), tyro-
sinase, and tyrosinase-related protein 1 (TRP-1). Moreover,
theophylline-induced action increased the levels of phos-
phorylated ERK and GSK3b (89).
Volatile organic compounds (VOCs)
VOCs are the important components for the aroma and
quality of the teas. Linalool and (Z)-hex-3-enal are the main
aroma compounds (90). Green tea contains various aliphatic
[(Z)-1,5-octadien-3-one, 4-mercapto-4-methyl-2-pentanone,
methional, (E,Z)-2,6-nonadienal, and 3-methylnonane-2,4-
dione) and heterocyclic (2-acetyl-1-pyrroline, 2-ethyl-3,5-
dimethyl pyrazine, 2,3-diethyl-5-methyl pyrazine, and 2-ace-
tyl-2-thiazoline] compounds (91). Aroma components are
present as glycoside derivatives that are liberated at the time
of oxidation and degradation (by glycosidases). Geranyl,
linolyl, terpinyl, and neryl glycosides are the components of
tea leaves (92). Hara et al. (93) reported that terpenoids and
hydrolyzed products of amino acids, carotenoids, and lino-
leic acid produced aroma compounds. Moreover, aldehydes,
alcohols, and some sulfur-containing compounds (94), and
degradation products of tannins and flavan-3-ols also give
aroma-active VOCs (95). Monoterpenoid compound gera-
niol improved metabolic syndrome. It enhanced PPAR-c
levels in adipose tissue of rats having metabolic syndrome.
Application of geraniol maintained the normal state of lipid
profile, systolic blood pressure, serum transaminases, cyto-
kines (IL-1b, TNF-a), NO levels, and hepatic lipid peroxida-
tion. Geraniol and pioglitazone co-treatment decreased
fasting glucose and triglycerides levels, improved insulin
sensitivity, and inhibited the effects of AGE products. All
these effects prevented the free radical-induced inflamma-
tory response during metabolic syndrome (96). Another
VOC compound nerolidol exhibited antioxidant and anti-
inflammatory effects (97). Detail structure, general proper-
ties, and physiological importance of different bioactive
components of tea leaves are furnished in Table 2.
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 13
Minerals and others
Tea leaves contain various types of minerals like fluorine,
manganese, nickel, selenium, molybdenum, iodine, alumi-
num, calcium, magnesium, sodium, potassium, and others
(98–100). The polysaccharides in association with proteins
and uronic acid are also the tea constituents (101). Different
monosaccharide units such as rhamnose, arabinose, galact-
ose, glucose, xylose, and mannose were identified in tea pol-
ysaccharides. Acidic components galacturonic acid and
glucuronic acid are the component of the pectic polysac-
charides (102). Fatty acids like linoleic and linolenic acids,
sterols (stigmasterol) are also the elemental part of the tea.
Chlorophyll and carotenoids are present as pigments (103).
Health beneficial effects of tea
Numerous studies have indicated that the bioactive com-
pounds of tea have various physiological benefits against
metabolic disorders (diabetes, obesity), oxidative stress, car-
diovascular diseases, neurodegenerative illness, cancer pro-
gression, inflammatory response, and gastric dysfunction
(Figure 1). The protective functions are mediated by regulat-
ing the metabolic activities, signaling pathways, expression
of various genes, and maintaining the redox homeostasis.
Protection against cardiovascular diseases
Cardiovascular diseases (CVD) are the leading non-commu-
nicable diseases all over the world. Different factors includ-
ing heredity, diet, stress, and lifestyle are the contributor to
CVD. Vascular inflammation and atherosclerosis are the
prime etiological events in CVD. The reactive oxygen species
(ROS) promote the oxidation of low-density lipoproteins
(LDL) in the area of vascular endothelium. Oxidized-LDL
(ox-LDL) attracts the monocytes/macrophages for adherence
on the surface of the endothelial cell layer. Monocytes start
the capturing of ox-LDL and appear as foam cells. These
foam cells start the formation of atherosclerotic plaques
(104, 105). Thus the dysfunction of endothelium potentiates
CVD. Epidemiological studies had revealed that consump-
tion of tea (particularly black tea) decreased plasma uric
acid, C-reactive protein (CRP), glucose, triglyceride, LDL/
HDL ratio, and plasma cholesterol levels (106). Bahorun
et al. (107) reported that supplementation of black tea
increased the blood flow in the brachial artery of patients
with CVD. Another component, theobromine altered the
plasma lipoprotein levels; it increased HDL-cholesterol levels
and reduced LDL concentration (108).
The oxidized (fermentation) products of catechins par-
ticularly epigallocatechin gallate (EGCG), theaflavins, thearu-
bigins, as well as the other components like quercetin,
kaempferol, and rutin were also recognized as the cardiopro-
tective agents (109, 110). They reduced oxidation of low-
density lipoprotein (LDL) and cholesterol. The randomized,
double-blind placebo-controlled study had revealed that con-
sumption of decaffeinated green tea extract capsules for
3 weeks reduced blood pressure, inflammation, oxidative
14 S. SAMANTA
Figure 1. Multipurpose health benefits of drinking of tea (Camellia sinensis).
stress, and total LDL cholesterol to the volunteers (111).
Green tea extracts exerted strong anti-oxidant properties. It
showed cardioprotective activities against doxorubicin
(DOX)-induced cardiotoxicity in rats. Green tea extract
restrained the levels of intracellular AST, CK, LDH, LPO,
and cytochrome P450. The enzymes of the antioxidant pro-
file like GPX, GR, GST, SOD, and CAT were also elevated
after taking green tea to increase antioxidant defense (112).
Similar findings on antioxidant properties were also
observed in the presence of major green tea catechin EGCG.
Additionally, EGCG suppressed the activity of NF-jB, p53,
caspases 3, 12, and maintained the Hsp70 levels to stop
the apoptosis of cardiomyocytes (113).
All the derivatives of theaflavins have antioxidant activity.
The in vitro study indicated that they prevented Cu2þ-medi-
ated LDL oxidation (114). Exogenous supplementation of
TF1 in apolipoprotein E knockout mice restricted the ath-
erosclerotic lesion by lowering the levels of ROS, leukotriene
B4 (LTB4), and plasma P-selectin (115). Moreover, it con-
trolled the mitochondrial permeability transition pore
(mPTP) opening to prevent apoptosis (116). TF3 can inhibit
plasminogen activator inhibitor type 1 (PAI-1). This effect
advances the activity of a plasminogen activator for the initi-
ation of fibrinolysis (106).
Hypertension is directly associated with CVD. The popu-
lation-based study indicated that consumption of green tea
exhibited anti-hypertensive effects decreased the risk of
CVD (13, 117, 118). Not only green tea, but black tea also
reduced both the systolic and diastolic pressure (119).
Kurita, et al. (120) observed that O-methylated EGCG (an
ingredient of tea) had potent inhibitory activity against
angiotensin-converting enzyme (ACE) resulting in

diminution of systolic blood pressure (SBP). The theaflavin
derivative theaflavin-3,30 -digallate improves acetylcholine
(ACh)-induced endothelium relaxation, reduces endoplasmic
reticulum (ER) stress, and modulates the activity of cysta-
thionine-b-synthase and cystathionine gamma-lyase to main-
tain the normal functions of the endothelium (121). L-
theanine can enhance the 5-hydroxytryptamine (5-HT) levels
at the peripheral nerve endings resulting in hypotensive
activity (79).
Caffeine and other methylxanthines inhibit phosphodies-
terases, increase intracellular cAMP levels, and NO synthesis
followed by relaxation of vascular smooth muscles and
maintenance of cardiac activity (87, 122, 123). Different
experimental studies indicated that tea ingredients regulated
the oxidative stress in endothelial cells and maintained the
vessel tone. Theaflavins (TF3) and EGCG reduce oxidative
stress markers like malondialdehyde (MDA) and dityrosine
levels. They also induce epithelial nitric oxide synthase for
the production of NO and vascular relaxation (124–126).
Thus, regular consumption of tea is protective against
hypertension and CVD.
Cancer preventive activities
Tea has potent anti-cancer effects. The mechanisms of onco-
static actions are mediated by different ways such as reduc-
tion of DNA damage and oxidative stress, scavenging of free
radicals, detoxification of carcinogens, and modulation of
carcinogenic gene expression (127). All the tea polyphenols
(except ()-epicatechin) exhibit the property of cell growth
inhibition (128). Moreover, flavonoids in tea may be
involved in the induction of apoptosis (129). The experi-
mental studies on the animal model had revealed that green
tea polyphenols were effective against the lung, oral cavity,
esophagus, stomach, small intestine, colon, bladder, liver,
pancreas, skin, prostate, and breast cancer. Green tea modu-
lates carcinogenesis by regulating the DNA methylation, his-
tone modification, micro-RNA activity, apoptosis, cell cycle,
invasion, and angiogenesis and metastasis (130–133).
Polyphenolic compound particularly EGCG alters metabolic
pathways, exhibits growth-inhibiting property, and anti-
angiogenic activity (134). Liu et al. (135) reported that spe-
cific amino acid theanine showed the anti-cancer property.
A report suggested that green tea decreased the 50% risk
of gastric cancer in the Chinese population (136). Similarly,
black tea exhibited strong protective actions against gastric
cancer in the Indian population (137). Raksit et al. (138)
had studied the effect of green tea liquor on cold-restraint
stress-induced gastric ulcer model in rats. They observed
that green tea liquor supplementation protected the gastric
mucosa from ulceration and improved the blood anti-oxi-
dant markers. The in vitro study on human gastric adeno-
carcinoma cell line SGC-7901 indicated that the volatile
compound of tea b-ionone arrested the cell cycle at the G0/
G1 phase. This component downregulated the activity of
MAPK pathway, decreased the expression of Cdk4, cyclin
B1, D1, and increased the levels p38 and p27 (139).
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 15
Drinking of green tea lowers the risk of breast cancer up
to 12% (140). Sufficient consumption of tea (three cups per
day) decreases the rate of incidence of breast cancer (141).
Catechins can inhibit the proliferation of breast cancer cells.
It has the ability to modulate the activity of molecular chap-
erones and telomerase; catechins regulate the redox homeo-
stasis and activate apoptotic cascade (142). EGC can induce
p53 independent apoptotic mechanism by activating Fas sig-
naling (143). However, contradictory reports were also avail-
able. Some reports suggested that tea consumption and tea
polyphenols were not associated with the reduction of risk
of breast cancer (144, 145).
Yang et al. (146) observed that the consumption of green
tea decreased the risk of colorectal cancer. The rate of intes-
tinal absorption of catechins is poor; therefore catechins
reach the colon in its native form where they inhibit the
activity of cancer-inducing nitrosamine compounds and het-
erocyclic amines (13). Application of catechin nanohybrids
in WM266 human melanoma significantly increased the rate
of apoptosis of tumor cells (147).
L-theanine has oncostatic effects. It inhibits glutamate
transport into the malignant cells and lowers the intracellu-
lar GSH content. This alteration recedes the drug resistance
property of cancer cells. The efflux of chemotherapeutic
agent doxorubicin occurs through the multidrug resistance-
associated protein-5/GS-X (MRP5/GS-X) pump. The limita-
tion of GSH blocks the activity of the pump that makes the
cancer cells more susceptible to cytotoxicity (148, 149).
Theanine derivatives ethyl 6-fluorocoumarin-3-carboxylyl L-
theanine (TFC) and ethyl 6-nitrocoumarin-3-carboxylyl L-
theanine (TNC) are used as an anticancer agent. Application
of these agents in lung cancer and cervical cancer block the
tumor growth by inhibiting the epidermal growth factor
receptor/vascular endothelial growth factor receptor-Akt/
nuclear factor-kappa B (EGFR/VEGFR-Akt/NF-kappa B)
signaling pathways (150, 151). Theanine decreased the via-
bility, invasion, and migration rate of human non-small cell
lung cancer cells A549 (135).
TFs (especially TF3) have an inhibitory effect on cell pro-
liferation and induce apoptosis (152). TFs-induced apoptotic
response was observed in mammary epithelial carcinoma
cells (153), and leukemia cells (154). TF2 induces the expres-
sion of pro-apoptotic protein p53 and Bax (155). The cell
culture study had revealed that TF3 can block cell prolifer-
ation by phosphorylating the EGF and PDGF in A431
human epidermoid carcinoma cells and mouse NIH3T3
fibroblast cells (156). Hepatic fibrosis increases the risk of
hepatocellular carcinoma (HCC). Consumption of black tea
is beneficial to protect HCC. Oral administration of black
tea extract diminished necrosis, bile duct proliferation,
inflammation in rat having dimethylnitrosamine-induced
fibrotic liver (157). Another unique catechin-dimer theasi-
nensin A suppressed the expression of hepatic a-smooth
muscle actin (a-SMA) and matrix metallopeptidase 9
(MMP-9) by inhibiting transforming growth factor b (TGF-
b) in carbon tetrachloride (CCl4) treated rats to stop the
hepatic fibrosis (158). Theasinensin A also induces apoptosis
cascade by decreasing mitochondrial transmembrane
16 S. SAMANTA
potential that advances the release of cytochrome c followed
by activation of caspase-9 and 3 in human histolytic
lymphoma (U937), and acute T-cell leukemia (JURKAT) cell
lines (159).
TFs are effective against ovarian cancer and act as risk-
reduction factor. All the derivatives of theaflavins have nega-
tive effects on ovarian cancer cell viability. The anti-cancer
effect is mediated by the induction of apoptosis. TFs modu-
late the activity of hypoxia-inducible factor 1a (HIF-1a) and
decrease the expression of vascular endothelial growth factor
(VEGF) (160). TF3 phosphorylates the checkpoint kinase 2
(Chk2) that modulates the action of p53-independent intrin-
sic and death receptors activated extrinsic apoptosis pathway
in OVCAR-3 cells. Moreover, TF3 stimulates the p27-medi-
ated G0/G1 cell cycle arrest (161). Black tea polyphenols
TF1, TF2, and TF3 inhibit ovarian and placental aromatase
activity. These polyphenols show antiproliferative effects in
transfected HER2/neu in MCF-7 breast cancer cells (162).
Prostate cancer is a leading problem in males.
Theaflavins of black tea influence mitochondrial dysfunction
to initiate apoptosis in PC-3 human prostate cancer cells
(163). Green tea extract is effective against prostate carcin-
oma (164) and colorectal cancer (165) as it contains high
amount of catechins particularly EGCG. Several case-control
and prospective studies had revealed that consumption of
green tea significantly reduced the rate of occurrence of
prostate cancer (PC) and exhibited protective measures
against PC [see review Miyata et al. (133)]. EGCG sup-
presses the growth of androgen-sensitive (LNCaP and
CWR22Rv1), and androgen-independent (DU-145 and PC-
3) PC cells (166–169). The oncostatic effect of EGCG is
mediated by the inhibition of acetylation of androgen recep-
tor and its translocation to the nucleus in androgen-depend-
ent prostate cancer cells (170). EGCG decreaseed ROS
production, protected DNA, and prevented angiogenesis
(35). In addition to cell culture experiments, the effects of
EGCG were also studied in in vivo system where it showed
anticancer properties in LNCaP 104-R1 (171) and
CWR22Rv1 (172) xenografts model in athymic nude mice.
The anticancer effects of EGCG and other polyphenols
on PC are multidimensional. EGCG induced apoptosis in
LNCaP and DU-145 cells (166, 167). Different derivatives of
EC suppressed the activity of PI3K, phospho-Akt, and
increased Erk1/2 in androgen-sensitive LNCaP and andro-
gen-independent DU-145 PC cells (173, 174) to initiate
apoptosis. Decreased levels of PI3K and phospho-Akt and
increased levels of Erk1/2 could be important approaches
for the treatment of prostate cancer (174). Moreover, EGCG
increased the levels of pro-apoptotic protein Bax or Bad,
stimulated the activity of p53, and reduced the expression of
Bcl-2 and Bcl-xL in LNCaP cells (175) and DU145 cells
(167). The in vivo experiment also reported a similar type of
apoptotic response after cancer cell implantation in athymic
nude mice (176). EGCG could arrest the cell cycle in the
G0/G1 phase in LNCaP and DU145 cells. This tea polyphe-
nol induced the expression of WAF1/p21, KIP1/p27, INK4a/
p16, and INK4c/p18, and suppressed the expression of
cyclin D1, cyclin E, Cdk2, Cdk4, and Cdk6 to regulate cell
cycle at the G1 phase (177).
Metastasis of cancer cells is most important for the pro-
gression of cancer. Znic-dependent enzyme matrix metallo-
proteinases (MMPs) is essential for remodeling the
extracellular matrix to facilitate metastasis. EGCG blocks the
expression and activation of MMP-2 and MMP-9 by sup-
pressing the phosphorylation of ERK1/2 and p38 in DU-145
cells (178). Supplementation of EGCG diminished the levels
of IGF-1 and IGFBP-3 in PC patients. IGF-1/IGFBP-3 ratio
is the crucial factor for the development of PC (133, 179).
EGCG downregulated the activity of NF-jB in the autoch-
thonous mouse PC model system. Administration of green
tea polyphenols inhibited the expression of IjB (inhibitor of
NF-jB) kinase a/b (IKK a/b), which took a critical part in
the activation of NF-jB cascade. Additionally, tea flavonoids
repressed the expression of receptor activator of NK-jB
(RANK), NK-jB inducing kinase (NIK), and signal trans-
ducer and activator of transcription (STAT)-3 in the pros-
tate cancer cells (180). Inhibition of NK-jB reduced
inflammatory response, COX-2 expression, tumor growth,
and angiogenesis (181, 182). Mukherjee et al. (183) reported
that EGCG modulated the expression of IL-6, IL-8, CXCL-1,
IP-10/CXCL-10, CCL-5, and TGF-b in LNCaP, DU145, and
PC-3 cells.
Several studies had been conducted to evaluate the effects
of green tea polyphenols on bladder cancer. EGCG can
arrest the cell cycle in transitional cell cancer (184).
Oxidative stress (OS) is the factor for cancer progression.
OS increases ROS that causes DNA damage, oncogene acti-
vation, and repression of tumor suppressor genes (133).
Green tea polyphenols fabricate protective measures against
OS as well as carcinogenesis (185). Like prostate cancer,
green tea polyphenols regulate the activity of PI3K/Akt sig-
naling (186), NF-jB pathway (187), decrease the expression
of Bcl-2 (186, 187), cyclin D1 and Cdk 4, 6 (184), and
increase the activation of caspases in bladder cancer cells
(187). Luo et al. (187) and Roomi et al. (188) suggested that
green tea polyphenols potentially controlled the MMPs
(MMP-9 and MMP-2) in SW780 and T24 bladder cancer
cell lines to prevent metastasis.
The volatile compound b-ionone is an anticancer agent.
The study on osteosarcoma cells U2OS had revealed that
b-ionone arrested the cell cycle at the G1/S phase. It dimin-
ished Bcl-2 levels, increased Bax concentration, cytochrome
c release, and subsequently advanced the activation of cas-
pase 3 to initiate apoptosis (189). b-Ionone prevents hepato-
cellular carcinoma (HCC). The protective effects of
b-ionone are mediated by reduction of lipid peroxidation,
induction of expression of Bax, PPAR-c, and FOXO-1; fur-
thermore, it downregulates Bcl-2 levels and Ki-67 expres-
sion (190).
Anti-obesity actions
Obesity is a common metabolic disorder where an imbal-
ance is present between energy intake and energy output.
Tea polyphenols may have some effects on the regulation of

obesity. The experimental result indicated that the adminis-
tration of green tea extract to the healthy male volunteers
stimulated sympathetic nervous system by reducing the nor-
adrenaline degradation. The subsequent effects are enhanced
beta-oxidation and excess energy expenditure (191, 192).
TFs suppressed lipogenesis by inhibiting the activity of fatty
acid synthase followed by the reduction of lipid accumula-
tion. The downregulation of the PI3K/Akt/Sp-1 pathway is
associated with this effect (193). Other polyphenolic com-
pounds EGCG of green tea, methylated EGCG of oolong tea
are also treated as anti-obesity factors. Catechins influence
the gut microbiota for the synthesis of short-chain fatty
acids (SCFAs) like acetate, propionate, and butyrate from
prebiotics. SCFAs activate AMP-mediated protein kinase to
enhance lipid metabolism (194).
Consumption of back tea showed anti-obesity action in
humans. Oral administration of black tea in mice induced
the expression and phosphorylation of liver kinase B1
(LKB1, a specific serine/threonine kinase) and adenosine
monophosphate-activated protein kinase (AMPK). At the
downstream level, these kinases regulated the metabolism
(glycolysis, lipid metabolism), cell growth, and cell prolifer-
ation. Black tea infusion also enhanced the rate of phos-
phorylation of acetyl-CoA carboxylase (ACC) that
allosterically inhibited the synthesis of fatty acids. Moreover,
the administration of black tea diminished the expression of
IL-1b, Cox-2, and iNOS. Altogether, black tea has the ability
to control the feeding pattern, lipid absorption, and obes-
ity (195).
Black tea polyphenols particularly TF3 inhibited the activ-
ity of pancreatic lipase resulting reduction of triacylglycerol
absorption and reduced the risk of postprandial hypertria-
cylglycerolemia (196). Catechins stimulated thermogenesis
and promoted the reduction of blood glucose as well as
body weight (197). Kudo et al. (198) reported that TF1
enhanced energy expenditure. TF1 induced the expression of
uncoupler protein 1 (UCP-1), and peroxisome proliferator-
activated receptor gamma coactivator-1a (PGC-1a) in brown
adipose tissue and gastrocnemius muscle to amplify the rate
of energy expenditure.
Antioxidant effects
The polyphenols of tea have antioxidant activities (65). The
structure of flavonoids is associated with antioxidant func-
tions. The o-dihydroxyl (30 and 40 OH group) catechol struc-
ture in the B-ring and the presence of a double bond
between two and three positions of C ring as well as the 4-
oxo group in the same ring facilitate the antioxidant activ-
ities of flavonoids. The hydroxyl groups of C3 and C5 of fla-
van-3-ol of tea polyphenols involve in hydrogen bonding to
provide antioxidant properties (199).
Green tea is the richest source of EGCG that has the
ROS scavenging property (200). Green tea preserves the
redox homeostasis by maintaining the reduced glutathione
(GSH) levels and the activity of glutathione peroxidase
(201). Theaflavins have strong free radical scavenging activ-
ity which is more effective than EGCG. Among the different
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 17
theaflavins, TF3 has the highest antioxidant property fol-
lowed by TF2 and TF1 (193, 202). TFs can control the for-
mation of protein carbonyl compound and promote the
utilization of the sulfhydryl group (-SH) to prevent the t-
BHP-induced oxidative stress (203).
Antidiabetic effects
Tea is recognized as an anti-diabetic agent. Green tea extract
decreases fasting glucose levels in blood (13). The clinical
trial established the insulinotropic effects of catechins. Tea
polyphenol EGCG induced postprandial insulin secretion
(204). Consumption of green tea increased insulin levels and
decreased glycosylated hemoglobin (HbA1c) concentra-
tion (205).
EGCG is the inhibitor of a-amylase and a-glucosidase
which is beneficial to control diabetes mellitus (206).
Hayashino et al. (207) reported that consumption of oolong
tea reduced the incidence of type 2 diabetes. A similar result
was also observed by Yang et al. (26). Theaflavins (specific-
ally TF1) and catechins can inhibit a-glucosidase and malt-
ase in the intestinal lumen that leads to decrease the
absorption of available monosaccharides. This action
ensured significant protective effects against diabetes melli-
tus (28, 208).
Black tea extracts have a direct effect on blood glucose
levels and carbohydrate metabolism. Application of black tea
extracts in streptozotocin treated diabetic rats restored insu-
lin levels, plasma glucose concentration as well as glycosy-
lated hemoglobin levels. The bioactive components
preserved the activity of hexokinase, and glucose-6-phos-
phate dehydrogenase; while, decreased the activity of glu-
cose-6-phosphatase, and fructose-1,6-bisphosphatase to
control the blood glucose levels. The activities of tricarb-
oxylic acid cycle enzymes (isocitrate dehydrogenase, malate
dehydrogenase, a-ketoglutarate dehydrogenase, and succin-
ate dehydrogenase) were also improved after the infusion of
black tea extracts (209).
Neuro-protection, mental well-being, and mood
enlivening functions
Caffeine and theobromine (methylxanthine) are the antagon-
ist of the adenosine receptors (210) that recognize as extra-
cellular adenosine molecule, a metabolic intermediate
appears as the hormone-like messenger. There are four sub-
types of adenosine receptors (A1, A2A, A2B, and A3).
Structurally, caffeine is very similar to adenosine molecules.
It inhibits phosphodiesterase to maintain the constant level
of cAMP. It also regulates intracellular calcium concentra-
tions (123, 211). Caffeine and theobromine act as psycho-
tropic agents (87, 212). Methylxanthines form a complex
with nucleic acid structure. This interaction alters the
expression of genes and the effects might be protective
against Alzheimer’s and Parkinson’s disease (213, 214).
Tea contains a particular amino acid, L-theanine which
has an important role in the central nervous system. This
amino acid alters the synthesis of dopamine and serotonin in
18 S. SAMANTA
the brain. These neurotransmitters advance the alpha-wave
activity which can be recorded by encephalography (EEG).
Continuation of alpha-wave indicates the relaxation of psy-
chophysiological effects (215). Theanine modulates the excita-
tory effects of caffeine (79) that improves mood, cognitive
functions and reduces stress, anxiety, and depression (216).
Different neurodegenerative disorders like Parkinson’s
(PD) and Alzheimer’s diseases (AD) are the social problem.
Theanine can cross the blood-brain barrier and regulates
brain neurotransmitter levels by modulating the AMPA
receptors (217). L-theanine decreased the glutamate uptake
in SH-SY5Y cells during in vitro culture, reduced Ab syn-
thesis, NOS activity and NO production, and neuronal
apoptosis; hence, this non-protein amino acid established
the possibilities of neuroprotective effects (218). Theanine
restored the valuable enzymes like superoxide dismutase,
and succinate dehydrogenase (SDH) to protect the neurons
from oxidative damage. Additionally, theanine blocked DNA
damage and apoptosis of the neural cells. Thus, the neuro-
protective effects rescued the neurons from neurotoxic
agents (219–221). Tamano et al. (222) reported that L-thea-
nine improved memory tracing by inhibiting the stress-
induced impairment of long-term potentiation (LTP) in the
hippocampal region. Theanine induced the NMDA receptor-
independent CA1 LTP in the hippocampus (223).
Black tea component theaflavic acid (TFA) is a protective
agent against cerebral ischemic stroke. TFA prevented the
oxygen and glucose deprivation/restoration (OGD/R)-induced
cellular injury and apoptosis in PC12 cells. Administration of
TFA decreased the ROS production, intracellular lactate
dehydrogenase (LDH) release, and increased SOD activity. To
maintain the antioxidant effects, TFA activated the nuclear
erythroid-2 related factor 2 (Nrf2)/ARE signaling pathway.
TFA influenced the translocation of Nrf2 to the nucleus and
facilitated its binding to the ARE that increased the expres-
sion of heme oxygenase-1 (HO-1). TFA restored the mito-
chondrial membrane potential, blocked the activation of
caspase-3 and Bax, and improved the levels of anti-apoptotic
factors Bcl-2. Thus, TFA exerted a preventive measure against
neuronal apoptosis (224).
Catechins exhibited anti-oxidative and anti-inflammatory
activity that reduced the risk of AD (16). EGCG suppressed
the accumulation of Huntingtin, amyloid-b, and a-synuclein
to decrease the prevalence of neurotoxicity. EGCG stimu-
lated glycogen synthase kinase-3b (GSK-3b), while inacti-
vated cytoplasmic non-receptor tyrosine kinase c-Abl/FE65.
Moreover, EGCG reduced ROS production, NF-jB activa-
tion, expression of TNFa, IL-1b, IL-6, and inducible nitric
oxide synthase (iNOS), MAPK/JNK/p38 signaling. It also
regulated the activity of intracellular antioxidants, nuclear
erythroid-2 related factor 2 (Nrf2), and heme oxygenase-1
(HO-1). All these events suppressed neurotoxicity and pro-
gression of AD (225–227).
Tea polyphenols modulated the activity of the circadian
clock component Bmal1 to control oxidative stress and neuro-
degenerative disorder. In vitro study had revealed that tea poly-
phenols were the natural inducer of Bmal1 synthesis in
neuronal cell lines SH-SY5Y. Tea polyphenols restored activity
of complex I-IV of the mitochondrial electron transport chain
to manage the oxidative stress. Tea polyphenols and Bmal1
synergistically controlled the Nrf2/ARE/HO-1 and Akt/CREB/
BDNF signaling pathway. Thus, tea polyphenols modulated the
circadian clock to prevent neurodegenerative diseases (228).
Tea volatile component nerolidol increased the activity of
SOD, CAT, and GSH content in rotenone treated rats. It
decreased the release of proinflammatory cytokines IL-1b,
IL-6, and TNF-a, and inflammatory mediators COX-2 and
iNOS in brain tissues of the treated rats. Moreover, it pre-
vented the loss of dopaminergic neurons in the substantia
nigra pars compacta. Thus, nerolidol protected the develop-
ment of Parkinson’s disease (229).
Antimicrobial property of tea components
Tea polyphenols had an impact on bacterial and viral infec-
tions (230). Catechins showed antimicrobial activity. They
were most effective against Gram-positive bacteria as com-
pared to Gram-negative bacteria (230, 231). Catechins easily
stuck with proteins and prevented the attachment of bacteria
and virus on the cell surface. You et al. (232) reported that
catechins could be used as a prophylactic agent for influenza
A (H1N1) infection. Consumption of black tea is protective
for the Helicobacter pylori infection; the bioactive compo-
nents reduced the rate of gastric infection (233–235).
Anti-inflammatory effects
Catechin-mediated experimental study on allergic rhinitis in
rats decreased the symptoms of the disease. Catechins
diminished IL-5, IL-13, and maintained the balance between
Th 2 and Th 1 cells. It had anti-thymic stromal lymphopoie-
tin (TSLP) activity and suppressed the action of NF-jB sig-
naling pathway. The reduction of NF-jBp65 subunit,
phosphorylation and translocation of p65-subunit to the
nucleus, and inhibition of IjBa degradation is the regulatory
processes of anti-inflammatory effects (236). Thus, catechin
directly prevented the inflammatory response.
Epicatechins have direct immunomodulatory actions on
neutrophils. The in vitro culture of neutrophils in the pres-
ence of different types of epicatechins (EC, EGC, ECG,
EGCG) showed the activities in favor of regulation of exag-
geration of inflammatory response. Epicatechins repressed
the expression of TLR4, NFjB, and iNOS, reduced TNF-a,
IL-1b and IL-6 levels, and myeloperoxidase (MPO) activity.
The production of ROS, NO, peroxynitrite, and HOCl also
decreased. Additionally, epicatechins increased the activity
of antioxidant enzymes (SOD, CAT, GPx, and GR) as well
as phagocytic capacity (237).
Theaflavins are the potent anti-inflammatory agent. They
can inhibit lipopolysaccharide-induced NF-jB and JNK acti-
vation as well as expression of cell adhesion molecule on the
surface of the epithelial cells (193). Theaflavins’ derivative
TF2B suppressed NF-jB activity and downregulated the
expression of COX-2, TNF-a, and iNOS (155).
The anti-inflammatory effects of caffeine were mediated
by inhibition of phosphodiesterases through nonselective
Table 3. A summarized report on possibilities of tea ingradients as an adjuvant in cancer therapy.
Types of cancer In vitro/in vivo study Chemotherapeutic agent Synergistic treatment Effect Mode of action References
Cervical cancer SiHa Bleomycin Tea polyphenols þ bleomycin # Cell growth " Intracellular ROS (257)
A glycopeptide, cleaved DNA " Apoptosis " Caspase 3, 8, 9 activity
strand (oxygen and metal " p53 activity
ions dependent), inhibit # Bcl-2
thymidine incorporation
Breast cancer MCF-7 Cisplatin Total tea # Cell growth " Intracellular ROS (258)
Crosslink with the purine polyphenols þ cisplatin " Apoptosis " Caspase 8, 9 activity
bases on the DNA resulting in " p53 overexpression
the DNA fragmenation and
preventing DNA repair
MCF-7 Sunitinib EGCG þ sunitinib " Anti-proliferative activity Downregulated IRS-1 levels (259)
Multi-targeted receptor # VEGF secretion Suppressed mitogenic effects
tyrosine kinase
In vivo Sunitinib EGCG þ sunitinib Greater tumor shrinkage Marked suppression of the IRS/
MCF-7 xenograft and anti-angiogenesis MAPK/p-S6K1 signaling
tumor models
ERa(þ) MCF-7, T47D, and Tamoxifen EGCG, EGC or ECG (5-25 EGCG (20 microM) elicited Arrest of cell cycle at the G2/M (260)
ERa(-) MDA-MB-231 and 4-hydroxytamoxifen (4-OHT) microM) in combination cytotoxicity in MCF-7 phase
HS578T cells Binds to the with 4-OHT (1 microM) EGCG (25 microM) Enhancement of drug sensitivity
estrogen receptor produced a greater Increase apoptosis
cytotoxic effect in MDA- Inhibit protein kinase C
MB-231 cells
Ovarian cancer A2780 (cisplatin sensitive Cisplatin Combinations of three trans- EGCG with TH5, TH6, and TH5, TH6, and TH7 produces (261)
and cisplatin-resistant palladiums (TH5, TH6, and TH7 showed tumor marked antagonism
A2780 (cisR cell lines TH7) þ EGCG antagonistic effects Cellular accumulation of
Cisplatin þ EGCG EGCG þ cisplatin platinum
mediated synergism High level of platinum-DNA
Overcoming binding and anti-tumor activity
drug resistance
A2780/CP70 and Cisplatin Cisplatin þ TF3 G1/S phase cell cycle Modulating the expression of cyclin (262)
OVCAR3 cells arrest A2, cyclin D1, cyclin E1, and
" Apoptosis CDK2/4
Regulating cleavage of caspase
3/7, cytochrome c, Bax
# Akt phosphorylation
M5076 ovarian Doxorubicin (DOX) DOX þ theanine " DOX concentration in Inhibition of MRP5/GS-X pump (252)
sarcoma cells DNA intercalating agent tumor cells Blocking of high-
inhibits topoisomerase Inhibition of affinity glutamate transporters,
II activity glutamate uptake GLAST and GLT-1
Inhibition of
glutathione-
DOX conjugate
Lung cancer PC-9 cell lines Celecoxib Cyclooxygenase- EGCG þ celecoxib " Apoptosis Activate ERK1/2 which upregulates (263)
2 inhibitor " Apoptosis related GADD153 expression
genes like DNA
damage-inducible 153
(GADD153) expression
H460, and H1975 cell lines Sunitinib EGCG þ sunitinib " Anti-proliferative activity Downregulated IRS-1 levels and (259)
# VEGF secretion suppressed mitogenic effects
In vivo Sunitinib EGCG þ sunitinib Greater tumor shrinkage Marked suppression of the IRS/
H460 xenograft and anti-angiogenesis MAPK/p-S6K1 signaling
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION

tumor models
(continued)
19
Table 3. Continued. 20
Types of cancer In vitro/in vivo study Chemotherapeutic agent Synergistic treatment Effect Mode of action References
Hepatocellular Hep3B cells 5-Fluorouracil (5-FU) EGCG þ 5-FU # Cell growth # COX-2 overexpression (264)
carcinoma (HCC) Thymidylate " Apoptosis # PGE2 secretion
synthase inhibitor
BEL-7404 cell line Doxorubicin (DOX) DOX þ ECG or DOX þ EGCG " Cell killing " Intracellular DOX accumulation (265)
In vivo " Chemo-sensitizing effect Inhibited P-gp efflux pump
S. SAMANTA

xenograft mouse model of DOX activity

" Topo II expression
# Expression of MDR1 and HIF-1alpha
mRNA
Unaltered GST protein levels in
tumor xenografts
Hep G2 cells Irinotecan Irinotecan þ epicatechins Epicatechins decreases the Catechins do not induce Cyt p450 (266)
Inhibitor of topoisomerase I (EGCG, ECG, EGC, and EC metabolic activation subtype CYP3A4 and also the
separate application) of irinotecan expression of UGT1A1
mRNA levels
Prostate cancer Prostate PC-3ML Taxane (i.e., paclitaxel and EGCG þ taxane " Apoptosis " Apoptotic genes p53, p73, p21 (267)
tumor cell docetaxel) expression
In vivo Stabilize GDP-bound tubulin in Intraperitoneal injection " Apoptosis " caspase 3
Preexisting tumor the microtubule resulting of EGCG þ taxane " Disease-free survival IC(50) values were 30 mM, 3 nM,
formation with PC-3ML disruption of microtubule rates and 6 nM, for EGCG, paclitaxel,
tumor cell and inhibition of the process # Metastases and docetaxel, respectively
of cell division
": increase; #: decrease; ER: estrogen receptor; IC: inhibitory concentration; MDR: multidrug resistance; PGE2: prostaglandin E2; P-gp: P-glycoprotein; UGT1A1: UDP-glucuronosyltransferase 1A1.

competitive inhibition. This effect raised the intracellular
cAMP concentrations followed by activation of protein kin-
ase A (PKA). The PKA-mediated phosphorylation modu-
lated the synthesis of TNF-a and other cytokines. Caffeine
downregulated the release of IL-2 and IFN-c from Th1 cells,
IL-4, IL-5 from Th2 cells. Caffeine metabolite paraxanthine
inhibited the chemotactic activity of neutrophils and mono-
cytes. These effects potentiated anti-inflammatory activ-
ity (238).
Others benefits
Gram-negative bacillus Porphyromonas gingivalis is the
causative agent of periodontitis where an infectious lesion of
the supporting structures of the teeth is the common symp-
tom. Bacterial infection increased the inflammatory response
by elevating IL-6, IL-8, and TNF-a levels, and also activated
the matrix metalloprotease (MMP) 1 and 2 which degraded
collagen and gelatin followed by tissue damage (239, 240).
TFs exhibited an antibacterial effect against P. gingivalis and
prevented the expression of MMP1 and MMP2 (241).
Consumption of tea is beneficial against arthritis. Hegarty
et al. (242) reported that drinking of tea improved bone
mineralization and density in aged women, and prevented
osteoporosis. Osteoporosis commonly occurs in postmeno-
pausal women. Osteoclasts involve in bone remodeling and
resorption of the bone matrix. Numerous matrix metallopro-
teases (MMP1, 2, 3, 8, 9, and others) are involved in matrix
dissolution (243). TF3 and EGCG repressed the expression
of MMPs particularly MMP2 and MMP9 to stop the demin-
eralization of the bone matrix. Moreover, TF3 arrested the
proliferation and differentiation of osteoclasts (244).
Differentiation of osteoclasts depends on DNA methylation.
The methylation reaction represses the expression of epigen-
etic-induced anti-osteoclastogenic genes. A specific enzyme
DNA methyltransferase 3a (Dnmt 3a) is involved in DNA
methylation process in the presence of S-adenosylmethio-
nine (SAM). Mice were deficient with Dnmt 3a exhibited a
fewer number of osteoclasts. TF3 blocked the activity of
Dnmt 3a to stop DNA methylation and avoided osteoclast-
mediated osteoporosis (245). Chen et al. (246) reported that
EGCG modulated the activity of the NF-jB RANK/RANK-
ligand/osteoprotegerin pathway to suppress the proliferation
of osteoclast as well as the activity of acid phosphatase.
Role of tea polyphenols as an adjuvant in
cancer therapy
Tea polyphenols have a promising role in cancer therapy.
There are huge possibilities to use the tea polyphenols as an
adjuvant with different chemotherapeutic agents (cisplatin,
doxorubicin, 5-FU, bleomycin, sunitinib, tamoxifen, irinote-
can, and taxane) for the study of various cancers like breast,
ovarian, cervical, hepatocellular, lung, and prostate cancer
in vitro model (247, 248). Tea polyphenols increased the
sensitivity of drug to the drug-resistance cancer cells and
enhanced the efficacy of the chemotherapeutic agents (249,
250). Non-protein amino acid theanine in association with
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 21
doxorubicin (DOX), reduced the adverse effects of anti-can-
cer treatment. Theanine promoted the formation of DOX-
GSH conjugate in the liver and enhanced the efflux of
DOX-GSH complex that decreased toxicity in the hepato-
cytes by lowering the concentration of DOX. Theanine
advanced the activity of glutaminase and gamma-glutamyl
transpeptidase to increases the glutamate and GSH levels
(251). Sugiyama and Sadzuka (252) reported that the com-
bination treatment of theanine and DOX in M5076 ovarian
sarcoma-bearing mice decreased the glutamate transport and
formation of DOX-glutathione conjugates resulting in
increased levels of DOX concentration in tumor cells.
Theanine restricted the lipid peroxidation (LPO) and main-
tained the glutathione peroxidase (GPx) activity. The various
functions of the tea components as an adjuvant are given in
Table 3.
Conclusion
From ancient times to the modern civilized world, tea is
used as a traditional drink for health promotional effects,
mental wellness, refreshment, as well as social culture. Tea
contained several biopharmaceutical compounds. These
compounds showed antioxidant, anti-inflammatory,
immune-modulatory, metabolic-regulatory, and cytoprotec-
tive properties for the promotion of health beneficial effects.
In recent times, people are more conscious about their
health, and the perception of tea consumption is gradually
changed. The consumption of tea is moving toward a func-
tional drink as it is becoming a promising agent for prophy-
lactic intervention in cardiovascular disorder, metabolic
diseases, neural damages, gastrointestinal problems, and
malignancy. Additionally, tea polyphenols have great possi-
bilities to use in cancer therapy as chemopreservatives in the
near future. Finally, it can be concluded that the regular
consumption of tea is the novel strategy for physiological
and mental wellness.
Acknowledgment
The author is grateful to Midnapore College, Midnapore, West Bengal,
India, for providing all kinds of facilities to prepare this manuscript.
The author expresses his sincere thanks to Dr. Amal Kanti
Chakraborty, Ex-Associate Professor of English, Midnapore College,
Midnapore for his help in the linguistic correction.
Disclosure statement
The author has no conflict of interest.
Funding
No financial grant was available. This review article was self-supported
by the author.
22 S. SAMANTA
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