ArticlePDF AvailableLiterature Review

Protective Mechanisms of Green Tea Polyphenols in Skin

Authors:

Abstract and Figures

Skin is frequently exposed to a variety of environmental, chemical, and genotoxic agents that contribute to disease and carcinogenesis. Ultraviolet light (UVR) is the main external stress that leads to immunosuppression, oxidative stress, premature aging, and tumor formation. Scientists and health professionals emphasize the importance of prevention strategies to circumvent such unfavorable outcomes. Plant polyphenols are a promising approach to disease prevention and treatment. Green tea is an abundant source of plant polyphenols that exhibit significant antioxidant, chemopreventive, and immunomodulatory effects in protecting the skin.
Content may be subject to copyright.
Hindawi Publishing Corporation
Oxidative Medicine and Cellular Longevity
Volume 2012, Article ID 560682, 8pages
doi:10.1155/2012/560682
Review Article
Protective Mechanisms of Green Tea Polyphenols in Skin
Patricia OyetakinWhite,1Heather Tribout,1and Elma Baron1, 2
1Department of Dermatology, University Hospitals Case Medical Center, Cleveland, OH 44106-5028, USA
2Department of Dermatology, Louis Stokes Cleveland Veterans Aairs Medical Center, Cleveland, OH 44106, USA
Correspondence should be addressed to Elma Baron, elma.baron@uhhospitals.org
Received 9 February 2012; Accepted 25 April 2012
Academic Editor: Luciano Pirola
Copyright © 2012 Patricia OyetakinWhite et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Skin is frequently exposed to a variety of environmental, chemical, and genotoxic agents that contribute to disease and
carcinogenesis. Ultraviolet light (UVR) is the main external stress that leads to immunosuppresion, oxidative stress, premature
aging, and tumor formation. Scientists and health professionals emphasize the importance of prevention strategies to circumvent
such unfavorable outcomes. Plant polyphenols are a promising approach to disease prevention and treatment. Green tea is an
abundant source of plant polyphenols that exhibit significant antioxidant, chemopreventive, and immunomodulatory eects in
protecting the skin.
1. Introduction
Ultraviolet radiation (UVR) is a major environmental source
of damage to the skin. Its eect on the skin’s biology
and immune system plays a major role in photoaging,
inflammation and carcinogenesis [1]. Approximately 3.5
million skin cancers are diagnosed annually in the United
States and the incidence of nonmelanoma (NMSC) increased
dramatically from 1996 to 2006 [2]. The morbidity and
economic burden of this malignancy is significant as the
estimated total direct costs for treatment of NMSC and
melanoma are $1.5 billion and $249 million, respectively [3,
4]. Sun avoidance, regular use of sunscreen, and protective
clothing are the recommended methods of preventing UVR-
induced damage but patient compliance is a major challenge.
For example, a recent study by Buller and colleagues surveyed
4837 adult skiers and snowboarders about their sunscreen
use and reapplication. Only 4.4% of adults were compliant
with the recommended guidelines of applying sunscreen up
to 30 minutes before sun exposure and reapplication every
2hours[5]. Therefore there is a need to identify additional
photoprotection strategies to engage the community at-large
about the importance and benefits of sun protection.
In the last few decades there has been a dramatic increase
in the use of plant and herbal supplements as people are
seeking dierent methods of disease prevention [6]. Green
tea consumption has become a popular trend in western
cultures as its beneficial eects in human disease have shown
promising results. Scientists searching for alternatives to
preventing and treating disease have recognized its powerful
beneficial eects in many organ systems. Green tea extracts
were found to be eective at suppressing environmentally
induced breast cancer [7], inhibiting T lymphocyte expan-
sion in autoimmune diseases [8], and suppressing inflam-
matory responses in coronary vessels in rodent experiments
[9]. Favorable results have also been demonstrated in skin
disease and carcinogenesis. Recent in vitro and in vivo animal
and human skin studies also showed its anti-inflammatory,
antioxidant, photoprotective, and chemopreventative eects
after topical application and oral consumption [1014]. This
review will discuss the chemical properties of green tea
that make it eective in skin biology and immunology and
how its mechanisms of action play a role in antioxidant,
photoprotective and chemopreventative functions in the
skin.
2. Background
Polyphenols are naturally occurring chemicals derived from
plants, fruits, nuts, and vegetables. They have been proven to
2Oxidative Medicine and Cellular Longevity
OH
O
OH
O
O
OH
OH
OH
OH
OH
HO
(a) ()-Epigallocatechin-3-gallate (EGCG)
OH
O
OH
OH
OH
OH
HO
(b) ()-Epigallocatechin (EGC)
OH
OH
O
OH
OH
HO
(c) ()-Epicatechin (EC)
OH
O
OH
O
O
OH
OH
OH
OH
HO
(d) ()-Epicatechin-3-gallate (ECG)
Figure 1: Structure of green tea polyphenols.
have many beneficial health benefits. Being widely abundant
and relatively inexpensive, the use of polyphenols is highly
attractive to researchers as a strategy for a cost-eective
alternative to current pharmacologic therapeutics [15]. Tea
is an important dietary source of plant polyphenols and next
to water it is the second most commonly consumed beverage
in the world. It is produced mainly from a single plant species
Camellia sinensis. The tea plant originated in Southeast Asia
over 4,000 years ago and is currently produced in over 35
countries with China, India, Sri Lanka, and Kenya generating
three-quarters of the world’s production. The six dierent
types of tea (white, yellow, green, oolong, black, and post fer-
mented teas) are categorized based on the wilting and enzy-
matic oxidization that takes place during processing [16].
There are three main types of polyphenols (flavonoids,
stilbenes, and lignans) that are classified by the num-
ber of phenol rings they contain and the binding
properties of the ring structures. The phenol rings
are comprised of phenyl and hydroxyl group struc-
tures that possess anti-inflammatory, immunomodulatory
and antioxidant properties [17]. Each class of polyphe-
nols can be further subclassified by the interactions of
their respective phenyl rings to carbon, oxygen, and
organic acid molecules [18]. This creates the huge diver-
sity of polyphenol compounds that can be found in
many naturally occurring food products. Flavonoids are
divided into 6 subclasses: flavonols, flavones, isoflavones,
flavanones, anthocyanidins, and flavanols. Majority of
the green tea polyphenols (GTPPs) are monomeric fla-
vanols called catechins. The four main catechin com-
pounds are ()-epigallocatechin-3-gallate (EGCG), ()-
epigallocatechin (EGC), ()-epicatechin-3-gallate (ECG),
and ()-epicatechin (EC) (Figure 1). EGCG is the most
abundant and extensively studied catechin with potent
therapeutic eects in skin.
3. Skin Damaging Effects of Ultraviolet Light
Sunlight is an important source of energy to sustain life.
However, except for vitamin D synthesis, it has several
harmful eects to the skin. Solar UVR can be divided into
three categories based on wavelength: UVA (320–400 nm),
Oxidative Medicine and Cellular Longevity 3
UVB (280–320 nm), and UVC (<280 nm). High energy short
wavelength UVC (<280 nm) and a portion of UVB (280–
295 nm) are absorbed by the ozone layer and atmosphere;
therefore it does not reach the Earth’s surface where it is
capable of causing extreme damage to DNA and biomolec-
ular molecules [19]. Longer wavelength UVB (295–320 nm)
makes up only 5–10% of atmospheric UVR but it has been
implicated in a variety of skin diseases, nonmelanoma and
melanoma skin cancers. DNA is a chromophore for UVB
and this direct interaction produces cyclobutane pyrimidine
dimers (CPD) and pyrimidine-pyrimidone (6–4) mutagenic
photoproducts that lead to tumor initiation and tumor pro-
motion [2022]. UVB also has indirect detrimental eects
on the skin’s immune system, oxidative stress responses, and
photoaging [22,23].
UVA radiation is far more abundant (90%) and pene-
trates much deeper into the epidermis and dermis of the
skin. It is weakly absorbed by DNA but reacts with other
nonDNA chromophores that lead to the formation of ROS
which damage DNA, proteins, and lipids in the skin [24
26]. Singlet molecular oxygen produced by UVA targets
DNA base guanine producing 8-oxo-7,8-dihydroguanine (8-
odHG) which is an important marker of oxidative stress [27,
28]. With the increased use of high-intensity UVA tanning
booths and UVB-absorbing sunscreens, human exposure
to UVA has become a public health concern [29]. UVA-
induced mutagenesis is still an area of debate; however, it
is clear it plays a significant role in producing bipyrimidine
photoproducts that have genotoxic eects [30]. In vivo
human studies have also demonstrated the immunosuppres-
sive eects of UVA and its increasing role in carcinogenesis
[31]. In order to avoid potential mutations, UVR-induced
DNA lesions are repaired by nucleotide excision repair
(NER) and base excision repair (BER) mechanisms before
DNA replication occurs. Additionally, stress signals created
by UVR trigger protective signaling responses in the cell
membrane, nucleus, and mitochondria that lead to cell cycle
arrest or apoptosis [3234]. Chronic and excessive UVR
exposure overwhelms and depletes these cutaneous defense
mechanisms. Therefore, compounds with antioxidant and
cell repair potential are promising additions to our sun
protection armamentarium.
4. Oral Consumption and Topical
Application of GTPP
Human and animal studies using both topical and oral
preparations of GTPP have shown significant protective
eects against UV-induced skin damage and immunosup-
pression. As an external organ system, skin allows for direct
pharmacological intervention with topical products. This
mode of delivery also minimizes the potential for systemic
toxicity. Topical application of EGCG in a hydrophilic
ointment demonstrated better photoprotective properties
versus oral consumption in mice [35]. In this in vivo study,
topical application provided significantly greater benefit
against UVB irradiation-induced depletion of antioxidant
enzymes and signaling protein phosphorylation. These pho-
toprotective functions of GTPP may be mediated through
interactions with inflammatory signaling molecules. Upon
UVR exposure Interleukin-12 (IL-12) is known to enhance
NER enzyme activity in keratinocytes [36]. Meeran et al.
proposed an IL-12-dependent mechanism of DNA repair
by topically applied EGCG [37]. In this study, UV-induced
suppression of CHS responses was maintained in IL-12
knockout mice in comparison to wild type mice. Subcuta-
neous injection with IL-12 three hours prior to UV exposure
in the IL-12 knockout mice diminished the amount of CPD
positive cells produced in contrast to the untreated group.
Earlier studies using topical and orally consumed GTPP in
mice decreased UVR-induced carcinogenesis, by inhibiting
the activity of chemical tumor initiators and promoters [38
40].
Recent studies by Katiyar et al. demonstrated a dose-
dependent decrease in UVR-induced immunosuppression
via contact hypersensitivity response (CHS) to 2, 4-
dinitrofluorobenzene in mice that were fed purified GTE
[41]. This decrease in immunosuppression was persistent
4 weeks after resumption of a normal liquid diet in the
animals. The authors further demonstrated that GTPs in
drinking water of UV-irradiated mice reduced the migration
of CPD positive cells to lymph nodes and improved the
NER mechanisms. Similar results were seen in adult human
subjects that ingested 7.5 mg of pure (commercially avail-
able) green tea brewed in 540 mL of boiling water. There
was a significant decrease in UVR-induced DNA damage
ofperipheralwhitebloodcells[42,43]. Human studies
using topically applied GTPP prior to exposure with 2-MED
of SSR demonstrated a decrease in SSR-induced erythema,
DNA damage, Langerhans cell damage, and production of 8-
OHdG in healthy human subjects [44,45].
5. Toxicity of GTPP
In general, GTPP has been shown to be well tolerated in
animal and human trials. Topical preparations have the
least harmful eects with minor irritation being the most
significant finding [46]; however, adverse eects of oral
consumption have been demonstrated. In a 9-month chronic
study in fasting Beagle dogs, oral ingestion of green tea
extract capsules caused unexpected morbidity and mortality
(16 deaths out of 24 treated animals) in the treated versus
control group resulting in early termination of the study
group [47]. Clinical signs of toxicity, weight loss were
observed as early by day 9 of this chronic study group
with fasting animals. Follow-up studies by the authors
demonstrated more favorable results when the green tea
capsules were administered in a fed state. Although the exact
mechanism of the toxicity was not determined, the authors
suggested gastrointestinal irritation, organ, and hematologic
evidence of immune-mediated hemolysis may have played a
role in the toxicity of ingesting a capsular form of the green
tea extracts. Studies by Isbrucker et al., where mice were fed
liquid and powered purified green tea extracts, did not show
any genotoxic eects [48].
In vitro culture experiments by Navarro-Peran et al.
showed that EGCG inhibits the activity of dihydrofo-
late reductase (DHFR) which is an important enzyme
4Oxidative Medicine and Cellular Longevity
in nucleotide biosynthesis [49]. The authors suggested
that this eective inhibition provides evidence for EGCG’s
chemotherapeutic mechanism of action. Their results pro-
vide an interesting insight into the reported association of
maternal tea consumption and neural tube defects [50].
There are a limited number of published studies showing
this teratogenic eect especially given the large amount of
tea consumed globally. Experiments evaluating reproductive
and developmental toxicity of EGCG in rats did not show
teratogenic eects [51].
6. Antioxidant Activity of GTPP in Skin
The skin has a complex defense system to deal with harmful
environmental and chemical substances but excessive or
chronic exposure can overwhelm the system leading to
oxidative stress and oxidative damage. In cells, reactive oxy-
gen species (ROS) are formed during the energy-producing
process of reducing molecular oxygen to water. These are
superoxide radicals (O2
•−), hydrogen peroxide (H2O2), and
hydroxyl radical (OH). An overproduction of ROS depletes
physiologic ROS-scavenging enzymes (superoxide dismu-
tase, and catalase) which cause damage to proteins, lipids,
and DNA [52] that contribute to skin diseases, immunosup-
pression, and development of skin cancer. GTPPs have been
shown to be eective in curbing these harmful eects because
their chemical structures can chelate metal ions and decrease
free radical damage to cellular structures [53,54].
Photoaging is caused by chronic UV exposure. In vitro
studies using cultured human skin fibroblasts pretreated with
GTPP showed a decrease in hydrogen peroxide (H2O2)-
induced ROS. In this study, the authors demonstrated
the ability of GTPP to improve fibroblast cell shape and
absolute cell numbers when compared to control groups
[10]. To assess the eect of GTE on lipid peroxidation
(LPO), Jorge et al. conducted an in vitro assay using
liposomal phophatidylcholine structure. They demonstrated
a significant decrease in the concentration of hydroperoxides
after a 3-hour reaction with an oxidative compound [55].
The inhibitory eect of GTPP on hydrogen peroxide
formation and cell signaling is paramount to its antioxidant
properties. There are few in vivo human studies demonstrat-
ing this protective event. In 2001, Katiyar and colleagues
demonstrated this protective eect in adult human volun-
teers exposed to a single dose of (4xMED) UV irradiation
prior to topical EGCG administration [56]. These authors
confirmed what is already known about EGCG inhibition
of UV-induced H2O2, NO and LPO production. They also
demonstrated blockage of UV-induced infiltration of ROS-
producing CD11b+cells and restoration of epidermal
antioxidant enzymes reduced glutathione, catalase, and
glutathione peroxidase.
7. Mechanism of Action of GTPP
Mitogen-activated protein kinases (MAPKs) are a group
of serine/threonine proteins that are involved in cellular
functions in the skin including cell growth, dierentiation,
proliferation, and apoptosis [57]. These proteins include
extracellular signal-regulated kinases (ERK), c-Jun NH2-
terminal kinases (JNK), and p38. MAPK signaling cascades
and downstream eectors are triggered in response to UVR-
induced oxidative and genotoxic stress. The activity of
GTPP is likely due to free radical scavenging activity that
prevents MAPK activation. Topical application of GTPP in
SKH-1 hairless mice showed inhibition of UVB-induced
phosphorylation of ERK1/2, JNK, and p38 expression [58].
These results were also seen in human dermal fibroblasts
where EGCG inhibited the UVB-induced activation of these
downstream eector pathways [59]. Bae et al. also demon-
strated the attenuation of nuclear transcription factors c-
Jun, p53, and c-fos within 30 mins of UVB irradiation
of the cultured cells. UVB-generated hydrogen peroxide
stimulates membrane epidermal growth factor receptors
(EGFRs) that activate ERK proteins which contribute to
cell proliferation and dierentiation that may be involved
in tumor promotion [60]. Pretreatment of normal human
epidermal keratinocytes (NHEKs) with EGCG prior to UVB
exposure inhibited H2O2production and phosphorylation of
ERK1/2, JNK, and p38 proteins [61]. Green tea extracts have
been implicated in immunoregulatory signaling functions.
Rodent experiments by Kim et al. demonstrated a dose-
dependent decrease in histamine production by peritoneal
mast cells incubated with GTPP [62]. Further experiments by
these authors proposed that the altered histamine release was
due to a GTE-mediated decrease in cAMP and calcium levels
which led to a NFκB and p38 MAPK-dependent inhibition
of proinflammatory cytokines, TNF-αand IL-6. Tabl e 1 lists
the major cellular and molecular targets of GTPP on normal
skin.
8. Role of GTPP in Chemoprevention
and Carcinogenesis
Cancer remains the second leading cause of death in the
United States [15]. Studies have shown that 30–40% of all
cases of cancers can be prevented by combining a healthy
diet, exercise, and maintaining a healthy body weight, and
more than 20% of all cases of cancer can be prevented
just by consuming an ample and varied amount of fruits
and vegetables [15,63]. EGCG has been shown to inhibit
tumor invasion and angiogenesis thereby preventing tumor
growth and metastasis [64]. Dermatologists are considerably
interested in green tea polyphenols (GTPP) as preventative
products for skin cancer, as their use have shown promising
results.
Skin cancer is the most common of all cancers; however
it is very preventable and curable if diagnosed early. Chronic
exposure to UVR is the key factor in initiating skin cancer.
UVB radiation induces both direct and indirect biologic
eects, including multiple eects on the immune system,
inducing oxidative stress, and damaging DNA, all in which
play an important role in the generation and maintenance of
neoplasms [65]. In vitro and in vivo systems have both shown
the protective eects from polyphenols on the biochemical
processes that are induced or mediated by UV radiation,
suggesting that routine use of polyphenols both topically and
Oxidative Medicine and Cellular Longevity 5
Tab le 1: Summary of eects of green tea polyphenols on skin.
GTPP protective eect Cellular and/molecular response References
UV protection
Inhibits UVB-induced MAPK activation and phosphorylation of ERK1/2, JNK
and p38. [5154,57]
Attenuates nuclear transcription factors, c-Jun p53, and c-fos
Antioxidant
Free radical scavenging activity
[35,48,53,54,56,57]
Inhibits NOS, H2O2production
Prevents UVB-induced depletion of antioxidant enzymes: catalase, glutathione
peroxidase, superoxide dismutase, and glutathione
Inhibits UVB-induced LPO and protein oxidation
Anti-inflammation
Prevents UV-induced depletion of CD1a + LC and APC Inhibits UV-
induced infiltration of monocytes, macrophages, neutrophils
[37,45,55,57,60]
Protects UVB-induced immunosuppression via IL-12 production
in histamine release by mast cells
Anticarcinogenesis
Inhibits DNA damage.
[45,48,59,60]
Inhibits UV-induced CPD, 8-OHdG formation
DNA repair enzyme activation
Modulates transcriptions factors AP1, NFKB
Inhibits tumor growth, progression and angiogenesis
LC: langerhans cells; LPO: lipid peroxidase; MAPK: mitogen-activated protein kinase; NOS: nitric oxide synthase.
orally may provide eective protection against UV radiation
and ultimately skin cancer [65].
Polyphenols are shown to possess anti-inflammatory,
immunomodulatory, and antioxidant properties [65]. EGCG
and green tea extract are non-toxic for humans and have a
wide range of target organs making it significantly dierent
than the standard form of preventative cancer drugs. Not
only is EGCG widely distributed throughout the body, but
studies also show that multiple oral administrations causes a
synergistic eect leading to higher concentrations of EGCG
in the cells. This eect was first seen in a study involving
mice, where 3H-EGCG was administered and measured in
the excretions. 24 hours after the intubation, radioactivity
was still found in multiple organs including the skin.
After multiple administrations of 3H-EGCG, radioactivity
increased 4–9 times in most organs, suggesting that routine
consumption or topical treatment may provide ecient
protection against UV radiation in humans. These results
eventually led to a study in humans, where researchers looked
at green tea consumption and the average age of cancer
onset. Cancer onset of male patients consuming more than
10 cups of green tea was approximately 3.2 years later than
male patients who consumed less than 10 cups of green
tea per day, and cancer onset for women drinking more
than10cupsofgreenteaperdaywas7.3yearslater.These
results allowed researchers to determine the eective cancer
preventative amount to be approximately 10 Japanese-size
cups (120 mL/cup) of green tea per day, which is equivalent
to about 2.5 g of green tea extract [66]. Another study
observed that regular intake of EGCG increased the minimal
dose of radiation required to induce erythema, suggesting
that the EGCG is able to strengthen the skin’s tolerance by
inhibiting the UV-induced skin damage from the radiation
[65]. From these findings it can be seen that orally consumed
EGCG has two dierent mechanisms of action and can act
as both a chemopreventive and photochemopreventive drug;
it can protect the body by suppressing, slowing down, and
reversing the process of carcinogenesis, as well as protecting
the skin from damaging radiation caused by harmful UVB
rays.
As mentioned before, UVB radiation induces oxidative
stress and DNA damage, and also aects the immune system.
In separate experiments, it has been shown that topical
treatments containing EGCG significantly inhibits acute or
chronic UV irradiation-induced protein oxidation in the
skin of mice, suggesting that GTTP’s may be able to reduce
photo damage in the skin and prevent premature aging
[45,65,67]. Another study showed that the pretreatment of
mouse skin with EGCG inhibited UVB-induced infiltration
of leukocytes, specifically CD11b+cells in the skin which
mediate UV-induced immunosuppression. These infiltrating
leukocytes can be a potential source of H2O2and NO which
play important roles in initiating and promoting tumor cells.
Less damage to the epidermal structure of the mouse skin
was also observed with the topical application of EGCG
before being exposed to UVB light. The data collected
in this study demonstrated the potent preventative eects
of topical EGCG in mice against UV radiation-induced
infiltration of leukocytes, suggesting that GTTP’s may have
preventative eects against the development of skin cancer
in humans [68]. Inflammatory responses are implicated in
skin disease, tumorigenesis, and tumor metastasis. EGCG
eectively inhibited human melanoma cell culture growth by
decreasing IL-1βsecretion and NFκBactivity[69].
9. Concluding Remarks
As discussed in this paper, GTPPs have important antiox-
idant, immunomodulatory, and photoprotective functions.
6Oxidative Medicine and Cellular Longevity
Their ability to modulate critical biochemical functions
through topical and oral formulations makes GTPPs a
promising candidate for chemoprevention and treatment of
disease. Future collaborative studies are needed to clarify
optimum dosing amounts that will provide therapeutic
benefits.
Conflict of Interests
The authors declare no conflict of interests.
References
[1] J. Hildesheim and A. J. Fornace, “The dark side of light: the
damaging eects of UV rays and the protective eorts of MAP
kinase signaling in the epidermis,DNA Repair, vol. 3, no. 6,
pp. 567–580, 2004.
[2] H. W. Rogers, M. A. Weinstock, A. R. Harris et al., “Incidence
estimate of nonmelanoma skin cancer in the United States,
2006,Archives of Dermatology, vol. 146, no. 3, pp. 283–287,
2010.
[3]D.R.Bickers,H.W.Lim,D.Margolisetal.,“Theburden
of skin diseases: 2004. A joint project of the American
Academy of Dermatology Association and the Society for
Investigative Dermatology,Journal of the American Academy
of Dermatology, vol. 55, no. 3, pp. 490–500, 2006.
[4] A. M. Seidler, M. L. Pennie, E. Veledar, S. D. Culler, and S.
C. Chen, “Economic burden of melanoma in the elderly pop-
ulation: population-based analysis of the Surveillance, Epi-
demiology, and End Results (SEER)-medicare data,Archives
of Dermatology, vol. 146, no. 3, pp. 249–256, 2010.
[5] D. B. Buller, P. A. Andersen, B. J. Walkosz et al., “Compliance
with sunscreen advice in a survey of adults engaged in outdoor
winter recreation at high-elevation ski areas,Journal of the
American Academy of Dermatology, vol. 66, no. 1, pp. 63–70,
2012.
[6]J.P.Kelly,D.W.Kaufman,K.Kelley,L.Rosenberg,T.E.
Anderson, and A. A. Mitchell, “Recent trends in use of herbal
and other natural products,Archives of Internal Medicine, vol.
165, no. 3, pp. 281–286, 2005.
[7] K. Rathore and H.-C. R. Wang, “Green tea catechin extract in
intervention of chronic breast cell carcinogenesis induced by
environmental carcinogens,Molecular Carcinogenesis, vol. 51,
no. 3, pp. 280–289, 2012.
[8] D. Wu, J. Wang, M. Pae, and S. N. Meydani, “Green tea EGCG,
T cells, and T cell-mediated autoimmune diseases,Molecular
Aspects of Medicine, vol. 33, no. 1, pp. 107–118, 2012.
[9] C. L. Shen, C. Samathanam, O. L. Tatum et al., “Green tea
polyphenols avert chronic inflammation-induced myocardial
fibrosis of female rats,Inflammation Research, vol. 60, no. 7,
pp. 665–672, 2011.
[10] J. I. Silverberg, J. Jagdeo, M. Patel, D. Siegel, and N. Brody,
“Green tea extract protects human skin fibroblasts from
reactive oxygen species induced necrosis,Journal of Drugs in
Dermatology, vol. 10, no. 10, pp. 1096–1101, 2011.
[11] D. S. Domingo, M. M. Camouse, A. H. Hsia et al., “Anti-
angiogenic eects of epigallocatechin-3-gallate in human
skin,International Journal of Clinical and Experimental
Pathology, vol. 3, no. 7, pp. 705–709, 2010.
[12] Y.-H. Hong, E. Y. Jung, K.-S. Shin et al., “Photoprotective
eects of a formulation containing tannase-converted green
tea extract against UVB-induced oxidative stress in hairless
mice,Applied Biochemistry and Biotechnology, vol. 166, no. 1,
pp. 165–175, 2012.
[13] T. Singh and S. K. Katiyar, “Green tea catechins reduce
invasive potential of human melanoma cells by targeting COX-
2, PGE2receptors and epithelial-to-mesenchymal transition,
PLoS ONE, vol. 6, no. 10, Article ID e25224, 2011.
[14] J. D. Liu, S. H. Chen, C. L. Lin, S. H. Tsai, and Y. C. Liang,
“Inhibition of melanoma growth and metastasis by combi-
nation with (-)-epigallocatechin-3-gallate and dacarbazine in
mice,Journal of Cellular Biochemistry, vol. 83, no. 4, pp. 631–
642, 2001.
[15] A. R. M. R. Amin, O. Kucuk, F. R. Khuri, and D. M. Shin,
“Perspectives for cancer prevention with natural compounds,
Journal of Clinical Oncology, vol. 27, no. 16, pp. 2712–2725,
2009.
[16] H. N. Graham, “Green tea composition, consumption, and
polyphenol chemistry,Preventive Medicine, vol. 21, no. 3, pp.
334–350, 1992.
[17]D.DelRio,L.G.Costa,M.E.J.Lean,andA.Crozier,
“Polyphenols and health: what compounds are involved?”
Nutrition, Metabolism and Cardiovascular Diseases, vol. 20, no.
1, pp. 1–6, 2010.
[18] C. Manach, A. Scalbert, C. Morand, C. R´
em´
esy, and L.
Jim´
enez, “Polyphenols: food sources and bioavailability,
American Journal of Clinical Nutrition, vol. 79, no. 5, pp. 727–
747, 2004.
[19] F. R. De Gruijl, “Skin cancer and solar UV radiation,European
Journal of Cancer, vol. 35, no. 14, pp. 2003–2009, 1999.
[20] D. L. Mitchell, “The relative cytotoxicity of (6-4) pho-
toproducts and cyclobutane dimers in mammalian cells,
Photochemistry and Photobiology, vol. 48, no. 1, pp. 51–57,
1988.
[21] G. A. Garinis, J. R. Mitchell, M. J. Moorhouse et al., “Tran-
scriptome analysis reveals cyclobutane pyrimidine dimers as
a major source of UV-induced DNA breaks,The EMBO
Journal, vol. 24, no. 22, pp. 3952–3962, 2005.
[22] L. Wang, V. S. Shirure, M. M. Burdick, and S. Wu, “UVB-
irradiation regulates VLA-4-mediated melanoma cell adhe-
sion to endothelial VCAM-1 under flow conditions,Molec-
ular Carcinogenesis, vol. 50, no. 1, pp. 58–65, 2011.
[23] S. L. Walker and A. R. Young, “An action spectrum (290-320
nm) for TNFαprotein in human skin in vivo suggests that
basal-layer epidermal DNA is the chromophore,Proceedings
of the National Academy of Sciences of the United States of
America, vol. 104, no. 48, pp. 19051–19054, 2007.
[24] E. Sage, P.-M. Girard, and S. Francesconi, “Unravelling UVA-
induced mutagenesis,Photochemical and Photobiological Sci-
ences, vol. 11, no. 1, pp. 74–80, 2012.
[25] T. M. R¨
unger and U. P. Kappes, “Mechanisms of mutation
formation with long-wave ultraviolet light (UVA),Photoder-
matology Photoimmunology and Photomedicine,vol.24,no.1,
pp. 2–10, 2008.
[26] F. R. De Gruijl, “Photocarcinogenesis: UVA vs. UVB radia-
tion,Skin Pharmacology and Applied Skin Physiology, vol. 15,
no. 5, pp. 316–320, 2002.
[27] J. Cadet, T. Douki, J. L. Ravanat, and P. Di Mascio, “Sensitized
formation of oxidatively generated damage to cellular DNA
by UVA radiation,Photochemical and Photobiological Sciences,
vol. 8, no. 7, pp. 903–911, 2009.
[28] J. Cadet and T. Douki, “Oxidatively generated damage to
DNA by UVA radiation in cells and human skin,Journal of
Investigative Dermatology, vol. 131, no. 5, pp. 1005–1007, 2011.
[29]H.W.Lim,W.D.James,D.S.Rigel,M.E.Maloney,J.
M. Spencer, and R. Bhushan, “Adverse eects of ultraviolet
Oxidative Medicine and Cellular Longevity 7
radiation from the use of indoor tanning equipment: time to
ban the tan,Journal of the American Academy of Dermatology,
vol. 64, no. 5, pp. 893–902, 2011.
[30] T. Douki, A. Reynaud-Angelin, J. Cadet, and E. Sage,
“Bipyrimidine photoproducts rather than oxidative lesions are
the main type of DNA damage involved in the genotoxic eect
of solar UVA radiation,Biochemistry, vol. 42, no. 30, pp.
9221–9226, 2003.
[31] E. D. Baron, A. Fourtanier, D. Compan, C. Medaisko, K. D.
Cooper, and S. R. Stevens, “High ultraviolet A protection
aords greater immune protection confirming that ultraviolet
A contributes to photoimmunosuppression in humans,Jour-
nal of Investigative Dermatology, vol. 121, no. 4, pp. 869–875,
2003.
[32] N. Pustiˇ
sek and M. ˇ
Situm, “Uv-radiation, apoptosis and skin,
Collegium Antropologicum,vol.35,no.2,supplement2,pp.
339–341, 2011.
[33] R. P. Rastogi, K. A. Richa, M. B. Tyagi, and R. P. Sinha, “Molec-
ular mechanisms of ultraviolet radiation-induced DNA dam-
age and repair,Journal of Nucleic Acids, vol. 2010, Article ID
592980, 32 pages, 2010.
[34] S. Courdavault, C. Baudouin, M. Charveron et al., “Repair of
the three main types of bipyrimidine DNA photoproducts in
human keratinocytes exposed to UVB and UVA radiations,
DNA Repair, vol. 4, no. 7, pp. 836–844, 2005.
[35] P. K. Vayalil, C. A. Elments, and S. K. Katiyar, “Treatment
of green tea polyphenols in hydrophilic cream prevents
UVB-induced oxidation of lipids and proteins, depletion of
antioxidant enzymes and phosphorylation of MAPK proteins
in SKH-1 hairless mouse skin,Carcinogenesis, vol. 24, no. 5,
pp. 927–936, 2003.
[36] A. Schwarz, S. St¨
ander, M. Berneburg et al., “Interleukin-12
suppresses ultraviolet radiation-induced apoptosis by induc-
ing DNA repair,Nature Cell Biology, vol. 4, no. 1, pp. 26–31,
2002.
[37] S. M. Meeran, S. K. Mantena, and S. K. Katiyar, “Prevention
of ultraviolet radiation—induced immunosuppression by (-)-
epigallocatechin-3-gallate in mice is mediated through inter-
leukin 12-dependent DNA repair,Clinical Cancer Research,
vol. 12, no. 7, part 1, pp. 2272–2280, 2006.
[38]Z.Y.Wang,R.Agarwal,D.R.Bickers,andH.Mukhtar,
“Protection against ultraviolet B radiation-induced photo-
carcinogenesis in hairless mice by green tea polyphenols,
Carcinogenesis, vol. 12, no. 8, pp. 1527–1530, 1991.
[39] W. A. Khan, Z. Y. Wang, M. Athar, D. R. Bickers, and H.
Mukhtar, “Inhibition of the skin tumorigenicity of (±)-7β,8α-
dihydroxy-9α,10α-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene
by tannic acid, green tea polyphenols and quercetin in Sencar
mice,Cancer Letters, vol. 42, no. 1-2, pp. 7–12, 1988.
[40] Z. Y. Wang, W. A. Khan, D. R. Bickers, and H. Mukhtar,
“Protection against polycyclic aromatic hydrocarbon-induced
skin tumor initiation in mice by green tea polyphenols,
Carcinogenesis, vol. 10, no. 2, pp. 411–415, 1989.
[41] S. K. Katiyar, M. Vaid, H. Van Steeg, and S. M. Meeran, “Green
tea polyphenols prevent uv-induced immunosuppression by
rapid repair of DNA damage and enhancement of nucleotide
excision repair genes,Cancer Prevention Research, vol. 3, no.
2, pp. 179–189, 2010.
[42] H. Malhomme de la Roche, S. Seagrove, A. Mehta, P.
Divekar, S. Campbell, and A. Curnow, “Using natural dietary
sources of antioxidants to protect against ultraviolet and
visible radiation-induced DNA damage: an investigation of
human green tea ingestion,Journal of Photochemistry and
Photobiology B, vol. 101, no. 2, pp. 169–173, 2010.
[43] N. Morley, T. Cliord, L. Salter, S. Campbell, D. Gould, and
A. Curnow, “The green tea polyphenol (-)-epigallocatechin
gallate and green tea can protect human cellular DNA from
ultraviolet and visible radiation-induced damage,” Photoder-
matology Photoimmunology and Photomedicine,vol.21,no.1,
pp. 15–22, 2005.
[44] C. A. Elmets, D. Singh, K. Tubesing, M. Matsui, S. Katiyar, and
H. Mukhtar, “Cutaneous photoprotection from ultraviolet
injury by green tea polyphenols,” Journal of the American
Academy of Dermatology, vol. 44, no. 3, pp. 425–432, 2001.
[45] M. M. Camouse, D. S. Domingo, F. R. Swain et al., “Topical
application of green and white tea extracts provides protection
from solar-simulated ultraviolet light in human skin,Experi-
mental Dermatology, vol. 18, no. 6, pp. 522–526, 2009.
[46] R. A. Isbrucker, J. A. Edwards, E. Wolz, A. Davidovich, and
J. Bausch, “Safety studies on epigallocatechin gallate (EGCG)
preparations. Part 2: dermal, acute and short-term toxicity
studies,Food and Chemical Toxicology, vol. 44, no. 5, pp. 636–
650, 2006.
[47] I. M. Kapetanovic, J. A. Crowell, R. Krishnaraj, A. Zakharov,
M. Lindeblad, and A. Lyubimov, “Exposure and toxicity
of green tea polyphenols in fasted and non-fasted dogs,
Tox i c o lo g y , vol. 260, no. 1–3, pp. 28–36, 2009.
[48] R. A. Isbrucker, J. Bausch, J. A. Edwards, and E. Wolz, “Safety
studies on epigallocatechin gallate (EGCG) preparations. Part
1: genotoxicity,Food and Chemical Toxicology, vol. 44, no. 5,
pp. 626–635, 2006.
[49] E. Navarro-Per´
an, J. Cabezas-Herrera, F. Garc´
ıa-C´
anovas, M.
C. Durrant, R. N. F. Thorneley, and J. N. Rodr´
ıguez-L ´
opez,
“The antifolate activity of tea catechins,Cancer Research, vol.
65, no. 6, pp. 2059–2064, 2005.
[50] A. Correa, A. Stolley, and Y. Liu, “Prenatal tea consumption
and risks of anencephaly and spina bifida,Annals of Epidemi-
ology, vol. 10, no. 7, pp. 476–477, 2000.
[51] R. A. Isbrucker, J. A. Edwards, E. Wolz, A. Davidovich, and
J. Bausch, “Safety studies on epigallocatechin gallate (EGCG)
preparations. Part 3: teratogenicity and reproductive toxicity
studies in rats,Food and Chemical Toxicology, vol. 44, no. 5,
pp. 651–661, 2006.
[52] M. Ott, V. Gogvadze, S. Orrenius, and B. Zhivotovsky,
“Mitochondria, oxidative stress and cell death,Apoptosis, vol.
12, no. 5, pp. 913–922, 2007.
[53] C. S. Yang, J. D. Lambert, and S. Sang, “Antioxidative and
anti-carcinogenic activities of tea polyphenols,Archives of
Tox i c o lo g y , vol. 83, no. 1, pp. 11–21, 2009.
[54] H. Wei, Q. Ca, R. Rahn, X. Zhang, Y. Wang, and M. Lebwohl,
“DNA structural integrity and base composition aect ultravi-
olet light-induced oxidative DNA damage,Biochemistry, vol.
37, no. 18, pp. 6485–6490, 1998.
[55] A. T. S. Jorge, K. F. Arroteia, J. C. Lago, V. M. De S´
a-Rocha, J.
Gesztesi, and P. L. Moreira, “A new potent natural antioxidant
mixture provides global protection against oxidative skin cell
damage,International Journal of Cosmetic Science, vol. 33, no.
2, pp. 113–119, 2011.
[56] S. K. Katiyar, F. Afaq, A. Perez, and H. Mukhtar, “Green tea
polyphenol (-)-epigallocatechin-3-gallate treatment of human
skin inhibits ultraviolet radiation-induced oxidative stress,
Carcinogenesis, vol. 22, no. 2, pp. 287–294, 2001.
[57] V. Muthusamy and T. J. Piva, “The UV response of the skin:
a review of the MAPK, NFκB and TNFαsignal transduction
pathways,Archives of Dermatological Research, vol. 302, no. 1,
pp. 5–17, 2010.
[58] F. Afaq, N. Ahmad, and H. Mukhtar, “Suppression of
UVB-induced phosphorylation of mitogen-activated protein
8Oxidative Medicine and Cellular Longevity
kinases and nuclear factor kappa B by green tea polyphenol
in SKH-1 hairless mice,Oncogene, vol. 22, no. 58, pp. 9254–
9264, 2003.
[59] J. Y. Bae, J. S. Choi, Y. J. Choi et al., “(-)Epigallocatechin gallate
hampers collagen destruction and collagenase activation in
ultraviolet-B-irradiated human dermal fibroblasts: involve-
ment of mitogen-activated protein kinase,Food and Chemical
Tox i c o lo g y , vol. 46, no. 4, pp. 1298–1307, 2008.
[60] D. Peus, A. Meves, R. A. Vasa, A. Beyerle, T. O’Brien, and M. R.
Pittelkow, “H2O2is required for UVB-induced EGF receptor
and downstream signaling pathway activation,Free Radical
Biology and Medicine, vol. 27, no. 11-12, pp. 1197–1202, 1999.
[61] S. K. Katiyar, F. Afaq, K. Azizuddin, and H. Mukhtar,
“Inhibition of UVB-induced oxidative stress-mediated phos-
phorylation of mitogen-activated protein kinase signaling
pathways in cultured human epidermal keratinocytes by green
tea polyphenol ( - )-epigallocatechin-3-gallate,Tox i c ol o g y a nd
Applied Pharmacology, vol. 176, no. 2, pp. 110–117, 2001.
[62] S. H. Kim, C. D. Jun, K. Suk et al., “Gallic acid inhibits
histamine release and pro-inflammatory cytokine production
in mast cells,Tox ic olo gi cal Sci ences , vol. 91, no. 1, pp. 123–131,
2006.
[63] M. J. Glade, “Food, nutrition, and the prevention of cancer:
a global perspective,Nutrition, vol. 15, no. 6, pp. 523–526,
1999.
[64] Y. D. Jung and L. M. Ellis, “Inhibition of tumour invasion
and angiogenesis by epigallocatechin gallate (EGCG), a major
component of green tea,International Journal of Experimental
Pathology, vol. 82, no. 6, pp. 309–316, 2001.
[65] J. A. Nichols and S. K. Katiyar, “Skin photoprotection
by natural polyphenols: anti-inflammatory, antioxidant and
DNA repair mechanisms,Archives of Dermatological Research,
vol. 302, no. 2, pp. 71–83, 2010.
[66] H. Fujiki, “Green tea: health benefits as cancer preventive for
humans,” Chemical Record, vol. 5, no. 3, pp. 119–132, 2005.
[67] S. K. Katiyar, A. Perez, and H. Mukhtar, “Green tea polyphenol
treatment to human skin prevents formation of ultraviolet
light B-induced pyrimidine dimers in DNA,Clinical Cancer
Research, vol. 6, no. 10, pp. 3864–3869, 2000.
[68] S. K. Katiyar and H. Mukhtar, “Green tea polyphenol (-)-
epigallocatechin-3-gallate treatment to mouse skin prevents
UVB-induced infiltration of leukocytes, depletion of antigen-
presenting cells, and oxidative stress,JournalofLeukocyte
Biology, vol. 69, no. 5, pp. 719–726, 2001.
[69] L. Z. Ellis, W. Liu, Y. Luo et al., “Green tea polyphenol
epigallocatechin-3-gallate suppresses melanoma growth by
inhibiting inflammasome and IL-1beta secretion,Biochemical
and Biophysical Research Communications, vol. 414, no. 3, pp.
551–556, 2011.
... The results presented in Figure 1 show that PEx, PG, and PN are cytotoxic at concentrations of 80 µg/mL and higher, whereas the cytotoxicity of EA started from the concentration of 20 µg/mL. The cytotoxic IC 50 Different concentrations of PEx, PG, PN, and EA, ranging from 1-320 µg/mL were applied in PBMC cultures and cytotoxicity was determined by the MTT test. The results presented in Figure 1 show that PEx, PG, and PN are cytotoxic at concentrations of 80 µg/mL and higher, whereas the cytotoxicity of EA started from the concentration of 20 µg/mL. ...
... The polyphenols present in blueberry inhibited the production of a number of proinflammatory cytokines, including IL-12 (a key IFN-g-inducing cytokine), in LPS-stimulated RAW264.7 macrophages [49]. Some studies also showed that IL-12 could be a target of polyphenols action and polyphenols-impaired inflammation could be due to the down-regulation of IL-12 production [50]. However, some opposing results have been published. ...
Article
Full-text available
Background: Our recent study has shown that pomegranate peel extract (PEx) showed significant immunomodulatory activity, which might be caused by ellagitannins. The aim of this work was to test the hypothesis that ellagitannin components act synergistically in the modulation of cytokine production. Methods: Human peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with phytohemagglutinin and treated with different concentrations of PEx or punicalagin (PG), punicalin (PN), and ellagic acid (EA), alone or with their combinations. Cytotoxicity, cell proliferation, and cytokine production were determined. Results: Non-cytotoxic concentrations of all compounds significantly inhibited cell proliferation. IC50 values (μg/mL) were: EA (7.56), PG (38.52), PEx (49.05), and PN (69.95). PEx and all ellagitannins inhibited the levels of TNF-α, IL-6, and IL-8, dose-dependently, and their combinations acted synergistically. PEx and all ellagitannins inhibited Th1 and Th17 responses, whereas the lower concentrations of PEx stimulated the production of IL-10, a Treg cytokine, as did lower concentrations of EA. However, neither component of ellagitannins increased Th2 response, as was observed with PEx. Conclusions: The combination of PG, PN, and EA potentiated the anti-inflammatory response without any significant synergistic down-modulatory effect on T-cell cytokines. The increased production of IL-10 observed with PEx could be attributable to EA, but the examined ellagitannins are not associated with the stimulatory effect of PEx on Th2 response.
... It is estimated that an average of about 120 mL of tea is consumed by a person per day, with higher amounts (about 540 mL per day) in Great Britain, which represents one of the largest consumers worldwide [1]. This interest arises from its nutritional and healing properties, which stimulate research to exploit tea for nutraceutical and pharmaceutical purposes [2]. ...
... In recent years, many studies have suggested beneficial properties of both topical and systemic application of green tea to ameliorate skin illness ( Figure 3). Preclinical studies highlighted the ability of green tea polyphenols to protect skin towards UV-induced damage and immunosuppression [2]. Moreover, GTPs have been shown to possess antimelanogenic properties, mediated by tyrosinase inhibition, and antiphotoaging and antiwrinkle ones [18], likely ascribed to their antioxidant power and to the ability to stimulate collagen and elastin production, while hindering degrading enzymes [19]. ...
Article
Full-text available
Green-tea-based products and their polyphenols, especially epigallocatechin-3-gallate, have attracted great attention over the years as possible nutraceuticals, due to their promising bioactivities, especially antioxidant and anti-inflammatory, which could be exploited in several diseases, including skin ailments. In this context, the present study aimed at reviewing clinical evidence about the benefits of the oral administration of green tea preparations and its polyphenols to relieve skin disorders, to point out the current knowledge, and to suggest possible novel strategies to effectively exploit the properties of green tea, also managing safety risks. To this end, a systematic review of the existing literature was carried out, using the PRISMA method. Few studies, including five focused on UV-induced erythema and skin alterations, three on photoaging, two on antioxidant skin defenses, and one on acne and genodermatosis, were retrieved. Despite several benefits, clinical evidence only supports the use of oral green tea preparations to protect skin from damage induced by ultraviolet radiation; in other cases, conflicting results and methodological limits of clinical trials do not allow one to clarify their efficacy. Therefore, their application as adjuvant or alternative sunscreen-protective interventions could be encouraged, in compliance with the safety recommendations.
... For instance, resveratrol has low bioavailability due to its nature of rapid metabolism in human body, resulting in inadequate role at the acting sites [7,21]. Moreover, effective and safe dose range of tea polyphenols is not yet determined, and vitamin C and E are potentially unstable due to the inherent instability and low penetrability of micronutrients to skin layers [19,22]. Photoelectric technologies, such as lasers and light-based treatments, are also employed to treat skin aging by promoting fibroblast proliferation and collagen synthesis [23]. ...
Article
Full-text available
Skin aging is a currently irreversible process, affected by increased oxidative stress, activated cellular senescence, and lacked regeneration of the dermal layer. Mesenchymal stem cells (MSCs), such as human umbilical cord-derived MSCs (hucMSCs), have pro-regeneration and anti-aging potencies. To explore whether hucMSCs can be used to treat skin aging, this study employed skin-aging model of nude mice to conduct in vivo assays, including biochemical analysis of superoxide dismutase (SOD) and malondialdehyde (MDA), gross observation, histopathological observation, and immunohistochemical analysis. To clarify how hucMSCs work on skin aging, this study employed skin-aging model of human dermal fibroblasts (HDFs) to conduct in vitro assays by applying conditional medium of hucMSCs (CMM), including wound healing assay, senescence staining, flow cytometric oxidative detection, real time PCR, and western blot analysis. The in vivo data demonstrated that hucMSCs dose-dependently removed wrinkles, smoothed skin texture, and increased dermal thickness and collagen production of aged skin by reversing SOD and MDA levels and up-regulating Col-1 and VEGF expressions, indicating anti-oxidative and pro-regenerative effects against skin aging. The in vitro data revealed that hucMSCs significantly reversed the senescence of HDFs by promoting cell migration, inhibiting ROS production, and restoring the overexpressions of oxidative and senescent markers through paracrine mode of action, and the paracrine mechanism was mediated by the inhibition of autophagy. This study provided novel knowledge regarding the anti-aging efficacy and paracrine mechanism of hucMSCs on skin, making hucMSCs-based therapy a promising regime for skin aging treatment. Graphical Abstract
... In addition, GT has shown positive effects in skin diseases and carcinogenesis. All these results have caused becoming a popular trend of GT consumption in western cultures in today (Gupta et al. 2009;OyetakinWhite et al. 2012;Mohabbulla Mohib et al. 2016). ...
Article
Full-text available
In this study, the toxic effects of paraquat, one of the most commercially sold herbicides in the world, and the protective role of green tea leaf extract (GTLE) against these effects were investigated. Allium cepa L. bulbs (n = 16) were used as test material. One hundred milligrams per liter dose of paraquat and 190 and 380 mg/L doses of GTLE were preferred. Paraquat toxicity was investigated with the help of physiological (percent germination, root length, and weight gain), cytogenetic (mitotic index = MI, micronucleus = MN, and chromosomal damages = CAs), biochemical (superoxide dismutase = SOD, catalase = CAT, malondialdehyde = MDA), and anatomical (meristematic cell damages) parameters. A. cepa bulbs were divided into 6 groups as 1 control and 5 applications. The control group was germinated with tap water, and the application groups were germinated with paraquat and two different doses of GTLE. Germination was carried out at room temperature for 72 h. At the end of the period, A. cepa bulbs were prepared for physiological, cytogenetic, biochemical, and anatomical analyzes using routine preparation techniques. As a result, paraquat application caused a decrease in physiological parameters and an increase in cytogenetic (except MI) and biochemical parameters. Compared to the control (group I), the germination percentage decreased by 38%, root length 12.5 times, and weight gain 5 times decreased in group IV treated with paraquat. MDA level increased 2.58 times, SOD activity 2.48 times, and CAT activity 4.51 times increased. Paraquat application caused a decrease in the percentage of MI and an increase in the number of MN and CAs. Paraquat application caused CAs in the form of fragment, sticky chromosome, unequal distribution of chromatin, bridge, nucleus with vacuoles, nucleus bud, and reverse polarization. In the meristematic cells of the root tips applied paraquat, unclearly vascular tissue, flattened cell nucleus, epidermis, and cortex cell deformation were observed. The application of GTLE together with paraquat caused an increase in the physiological parameter values and a decrease in the cytogenetic (except MI) and biochemical parameter values. An improvement in the severity of damages induced by paraquat was also observed in root tip meristematic cells. It was determined that the improvements observed in all these parameters were related to the dose of GTLE applied. The 380 mg/L dose of GTLE provided more protection than the 190 mg/L dose. Compared to group IV in which paraquat was applied, the germination percentage increased by 21%, root length 5.83 times, and weight gain 2.92 times increased in group VI administered 380 mg/L dose of GTLE. In addition, MDA level decreased 1.78 times, SOD activity 1.59 times and CAT activity 1.65 times. In conclusion, paraquat administration at a dose of 100 mg/L caused physiological, cytogenetic, biochemical, and anatomical toxicity in A. cepa bulbs. GTLE application, on the other hand, resulted in improvements in the severity of this toxicity induced by paraquat, depending on the dose. Therefore, GTLE can be used as an effective nutritional supplement to reduce or prevent the toxicity caused by environmental agents such as pesticides.
... The human immune system has developed defensive components possessing functions specialized for mucosal areas, such as mucus and its constituents, secretory immunoglobulins, and unique subsets of leukocytes localizing to or maturating in mucosal regions [1]. Mucosal surfaces are the interfaces between the external and internal environments, through which gases, nutrients, waste products, and other materials can move [2]. At the same time, mucosal surfaces also provide ideal sites for the entry of pathogens. ...
Article
Full-text available
Green tea and its bioactive components, especially polyphenols, possess many health-promoting and disease-preventing benefits, especially anti-inflammatory, antioxidant, anticancer, and metabolic modulation effects with multi-target modes of action. However, the effect of tea polyphenols on immune function has not been well studied. Moreover, the underlying cellular and molecular mechanisms mediating immunoregulation are not well understood. This review summarizes the recent studies on the immune-potentiating effects and corresponding mechanisms of tea polyphenols, especially the main components of (–)-epigallocatechin-3-gallate (EGCG) and (–)-epicatechin-3-gallate (ECG). In addition, the benefits towards immune-related diseases, such as autoimmune diseases, cutaneous-related immune diseases, and obesity-related immune diseases, have been discussed.
Article
Full-text available
The physiological and morphological aspects of skin suffer from frequent change. Numerous internal and external factors have direct impact on inducing various skin problems like inflammation, aging, cancer, oxidative stress, hyperpigmentation etc. The use of plant polyphenols as a photo-ecting agent is gaining popularity nowadays. Polyphenols are known to enhance endogenic antioxidant system of skin thereby preventing various skin diseases. The biological activity of plant polyphenols is dependent on their physicochemical properties for overcoming the epidermal barriers to reach the specific receptor. Several evidences have reported the vital role polyphenols in mitigating adverse skin problems and reverting back the healthy skin condition. The interest in plant derived skin care products is emerging due to the changing notion of people to shift their focus towards use of plant-based products. The present review draws an attention to uncover the protective role of polyphenols in prevention of various skin problems. Several in vitro and in vivo studies have been summarized that claims the efficacious nature of plant extract having dermatological significance.
Article
Full-text available
Daun teh hijau (Camellia sinensis (L.) Kuntze) diketahui mengandung polifenol yang mampu bertindak sebagai fotoprotektif, antipenuaan, antioksidan, antiinflamasi, dan antikarsinogen. Penggunaan daun teh hijau agar mudah diaplikasikan ke kulit dapat dibuat menjadi sediaan krim. Penelitian ini dilakukan untuk mengetahui pengaruh penggunaan emulgator perpaduan asam stearat dan trietanolamin terhadap sifat fisik krim dan mengetahui formula terbaik krim ekstrak etanol daun teh hijau. Krim diformulasi dengan kombinasi asam stearat dan trietanolamin, yaitu F1 (7% : 2%), F2 (10% : 3%), F3 (13% : 4%). Ekstrak daun teh hijau diperoleh melalui ekstraksi metode maserasi dengan etanol 70%. Hasil penelitian ini menunjukkan bahwa perpaduan asam stearat dan trietanolamin memengaruhi bentuk sediaan, viskositas, daya sebar, dan pH sediaan krim. Semua formula menunjukkan warna hijau kecoklatan, bentuk setengah padat, bau khas, dan homogen sebelum dan sesudah penyimpanan dipercepat. Viskositas berkisar antara 7383–9116 cps sebelum penyimpanan dan 7100–9500 cps setelah penyimpanan, daya sebar berkisar antara 5,50–7,23 cm sebelum penyimpanan dan 5,33–7,00 cm setelah penyimpanan, pH berkisar antara 6,60–7,20 sebelum penyimpanan dan 7,30–7,70 setelah penyimpanan. Formulasi terbaik yang diperoleh adalah F3 (asam stearat 13% dan trietanolamin 4%).
Article
Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including skin cancers, acne, photoaging, cutaneous wounds, scars, alopecia, psoriasis, atopic dermatitis, and microbial infection. In particular, there has been an increasing interest in the discovery of cosmetic applications using catechins as the active ingredient because of their antioxidant and anti-aging activities. However, active molecules with limited lipophilicity have difficulty penetrating the skin barrier, resulting in low bioavailability. Nevertheless, topical application is a convenient method for delivering catechins into the skin. Nanomedicine offers an opportunity to improve the delivery efficiency of tea catechins and related compounds. The advantages of catechin-loaded nanocarriers for topical application include high catechin loading efficiency, sustained or prolonged release, increased catechin stability, improved bioavailability, and enhanced accumulation or targeting to the nidus. Further, various types of nanoparticles, including liposomes, niosomes, micelles, lipid-based nanoparticles, polymeric nanoparticles, liquid crystalline nanoparticles, and nanocrystals, have been employed for topical catechin delivery. These nanoparticles can improve catechin permeation via close skin contact, increased skin hydration, skin structure disorganization, and follicular uptake. In this review, we describe the catechin skin delivery approaches based on nanomedicine for treating skin disorders. We also provide an in-depth description of how nanoparticles effectively improve the skin absorption of tea catechins and related compounds, such as caffeine. Furthermore, we summarize the possible future applications and the limitations of nanocarriers for topical delivery at the end of this review article.
Article
The potential role of plant-based foods in the promotion of skin health is an emerging area of nutrition research. Plant-based foods are rich in bioactive compounds, including vitamin C, vitamin E, beta-carotene, polyphenols, and phenolic acids, which can contribute to oxidant defense, lower inflammation, and promote structural support of the skin. Epidemiological studies have associated higher intakes of select fruits and vegetables with positive skin health.1,2 Beneficial effects of certain fruits, vegetables, nuts, legumes, and polyphenolic-rich beverages on the skin have been reported, with each of these providing a unique phytochemical composition. While most studies use extracts, this review will focus on data from whole foods and minimally processed products. Collectively, the evidence to date suggests a promising future for plant-based dietary interventions that promote skin barrier health and function. However, additional research is required to address issues such as the optimal quality and duration of intake as well as potential mechanisms. Studies in the above areas will help formulate specific targeted dietary recommendations.
Article
Full-text available
Skin disease is one of the top 15 groups of medical conditions for which prevalence and health care spending increased the most between 1987 and 2000, with approximately 1 of 3 people in the United States with a skin disease at any given time. Even so, a national data profile on skin disease has not been conducted since the late 1970s. This study closes the gap by estimating the prevalence, economic burden, and impact on quality of life for 22 leading categories of skin disease. The estimated annual cost of skin disease in 2004 was $39.3 billion, including $29.1 billion in direct medical costs (costs of health services and products) and $10.2 billion in lost productivity costs (defined as costs related to consumption of medical care, costs associated with impaired ability to work, and lost future earning potential because of premature death). Based on a methodology of willingness to pay for symptom relief, the additional economic burden of skin disease on quality of life amounted to an estimated $56.2 billion. Including the economic burden on quality of life, the total economic burden of skin disease to the US public in 2004 was approximately $96 billion.
Article
Full-text available
Melanoma is the most serious type of skin disease and a leading cause of death from skin disease due to its highly metastatic ability. To develop more effective chemopreventive agents for the prevention of melanoma, we have determined the effect of green tea catechins on the invasive potential of human melanoma cells and the molecular mechanisms underlying these effects using A375 (BRAF-mutated) and Hs294t (Non-BRAF-mutated) melanoma cell lines as an in vitro model. Employing cell invasion assays, we found that the inhibitory effects of green tea catechins on the cell migration were in the order of (-)-epigallocatechin-3-gallate (EGCG)>(-)-epigallocatechin>(-)-epicatechin-3-gallate>(-)-gallocatechin>(-)-epicatechin. Treatment of A375 and Hs294t cells with EGCG resulted in a dose-dependent inhibition of cell migration or invasion of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2, prostaglandin (PG) E(2) and PGE(2) receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, also inhibited melanoma cell migration. EGCG inhibits 12-O-tetradecanoylphorbol-13-acetate-, an inducer of COX-2, and PGE(2)-induced cell migration of cells. EGCG decreased EP2 agonist (butaprost)- and EP4 agonist (Cay10580)-induced cell migration ability. Moreover, EGCG inhibited the activation of NF-κB/p65, an upstream regulator of COX-2, in A375 melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, also inhibited cell migration. Inhibition of melanoma cell migration by EGCG was associated with transition of mesenchymal stage to epithelial stage, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin, cytokeratin and desmoglein 2) and a reduction in the levels of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in A375 melanoma cells. Together, these results indicate that EGCG, a major green tea catechin, has the ability to inhibit melanoma cell invasion/migration, an essential step of metastasis, by targeting the endogenous expression of COX-2, PGE(2) receptors and epithelial-to-mesenchymal transition.
Article
The effect of pretreatment of skin of Sencar mice with topically applied tannic acid, quercetin and green tea polyphenols (GTP) on the skin tumor initiating activity of (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-2) has been evaluated. The animals were pretreated with the plant phenols (tannic acid and quercetin (3000 nmol) or GTP 24 mg/mouse) for 7 days after which they received a single topical application of 200 nmol of BPDE-2 as the initiating agent. Beginning 7 days following initiation animals received twice weekly applications of 3.24 nmol of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Tannic acid and GTP afforded significant protection against skin tumor induction. These inhibitory effects were verified both by prolongation of the latency period and subsequent development of tumors. Quercetin, on the other hand, afforded only moderate protection. Each phenolic compound was found to be highly effective in accelerating the disappearance of BPDE-2 from aqueous medium. Our results suggest that tannic acid and GTP have substantial potential for protecting against the skin tumorigenic response to BPDE-2 and the mechanism of inhibition may involve inactivation of the reactive carcinogenic moiety.
Article
The following article critiques a report on the link between diet and cancer recently prepared by an expert panel and sponsored and published by the American Institute for Cancer Research and the World Cancer Research Fund. The report can be found on the Web at http://www.aicr.org/report2.htm.
Article
Abstract— The significance of the pyrimidine(6-4)pyrimidone photoproduct in mammalian cell killing is considered. Photochemical data indicate that the(6–4) photoproduct is induced at a substantial frequency compared to the cyclobutane dimer and that the action spectra for the induction of both lesions are equivalent. The repair of(6–4) photoproducts in various normal and UV-hypcrsensitive mammalian cell lines, including several recently derived somatic cell hybrids and transformants, is presented. The sensitivity of these cells to ultraviolet irradiation correlates better with the capacity to repair(6–4) photoproducts than cyclobutane dimers. These data are used to support that idea that the(6–4) photoproduct is one of the major cytotoxic lesions induced in DNA by ultraviolet light.
Article
Apoptosis or programmed cell death is a key function in regulating skin development, homeostasis and tumorigenesis. The epidermis is exposed to various external stimuli and one of the most important is UV radiation. The UVA and UVB spectra differ in their biological effects and in their depth of penetration through the skin layers. UVB rays are absorbed directly by DNA which results in its damage. UVA can also cause DNA damage but primarily by the generation of reactive oxygen species. By eliminating photodamaged cells, apoptosis has an important function in the prevention of epidermal carcinogenesis. UV-induced apoptosis is a complex event involving different pathways. These include: 1. activation of the tumour suppressor gene p53; 2. triggering of cell death receptors directly by UV or by autocrine release of death ligands; 3. mitochondrial damage and cytochrome C release. The extrinsic pathway through death receptors such as fibroblast-associated, tumour necrosis factor receptor and TNF related apoptosis inducing ligand receptor activate caspase cascade. The intrinsic or mitochondrial pathway of apoptosis is regulated by the Bcl-2 family of proteins, anti-apoptotic (Bcl-2, Bcl-xl, Bcl-w) and the pro-apoptotic (Bax, Bak, Bid). The balance between the pro-apoptotic and anti-apoptotic proteins determines cell survival or death. We discuss recent findings in the molecular mechanisms of UV induced apoptosis.
Article
Ultraviolet B (UVB) irradiation may induce the acceleration of skin aging. The purpose of this study was to develop an effective formulation containing tannase-converted green tea extract (FTGE) to inhibit UVB-induced oxidative damage. Significant (p<0.05) prevention of the reduced form of glutathione (GSH) depletion was observed in mice treated with FTGE. The hydrogen peroxide levels of mice treated with FTGE were similar to those of UVB non-irradiated mice. No significant difference was observed between No UVB control and FTGE mice. Also, mice treated with FTGE had significant (p<0.05) decreases in thiobarbituric acid-reactive substance levels by lipid peroxidation compared with No UVB control mice. Our data suggest that this formulation may be effective in protecting skin from UVB photodamage.