Content uploaded by Raimundo Gonçalves de Oliveira Junior
Author content
All content in this area was uploaded by Raimundo Gonçalves de Oliveira Junior on Feb 28, 2017
Content may be subject to copyright.
Vol. 10(47), pp. 848-864, 20 December, 2016
DOI: 10.5897/JMPR2016.6273
Article Number: C1278AB62177
ISSN 1996-0875
Copyright © 2016
Author(s) retain the copyright of this article
http://www.academicjournals.org/JMPR
Journal of Medicinal Plants Research
Review
Flavonoids as photoprotective agents: A systematic
review
José Marcos Teixeira de Alencar Filho1,2, Pedrita Alves Sampaio2, Emanuella Chiara Valença
Pereira2, Raimundo Gonçalves de Oliveira Júnior1,2, Fabrício Souza Silva1, Jackson Roberto
Guedes da Silva Almeida1,2, Larissa Araújo Rolim2, Xirley Pereira Nunes1,2 and
Edigênia Cavalcante da Cruz Araújo1,2*
1Núcleo de Estudos e Pesquisas de Plantas Medicinais (NEPLAME), Universidade Federal do Vale do São Francisco,
Brazil.
2Central de Análises de Fármacos, Medicamentos e Alimentos (CAFMA), Universidade Federal do Vale do São
Francisco, Brazil.
Received 13 October, 2016; Accepted 5 December, 2016
There is a growing need for research of photoprotective molecules from natural sources. Flavonoids
have shown significant absorption in ultraviolet A (UVA), ultraviolet B (UVB) region, due to their
chemical structure with conjugated double bonds, and may be used as ingredients in cosmetics
formulations for skin protection. This systematic review reports what has been researched over the
past decade on flavonoid and photoprotective activity, as well as some mechanisms of action by which
these metabolites act. The search was conducted in three databases (Science Direct, PubMed and
Scopus) using the descriptors “flavonoid”, “photoprotection” and “sunscreen” combined, published
between January 2006 and January 2016. Twenty-two articles were selected and 17 flavonoids were
cited. The data reviewed here indicate that flavonoids are potential in the fight against UVA and UVB
radiation and which may be used as adjuvants in photoprotective formulations.
Key words: Ultraviolet (UV), induced damage, natural products, flavonoids photoprotective activity, ultraviolet
radiation.
INTRODUCTION
Sunscreens are mainly used to prevent the formation of
erythema arising from exposure to sunlight. Reducing the
amount of ultraviolet (UV) radiation reaching the skin by
sunscreens may also reduce the risk of skin cancer
induced by sun. The UV spectrum is divided into three
groups based on wavelength: Ultraviolet C (UVC) that
ranges 100 to 290 nm, ultraviolet B (UVB), 290 to 320
nm, and ultraviolet A (UVA), 320 to 400 nm. UVA is
subdivided into UVA2 (320 to 340 nm) and UVA1 (340 to
400 nm). The solar UV radiation on Earth's surface is
approximately 90 to 99% UVA and 1 to 10% UVB
(Gardiner et al., 2006; Verschooten et al., 2006;
*Corresponding author. E-mail: edigenia.araujo@univasf.edu.br. Tel: (+55 87) 99966-2832.
Author(s) agree that this article remain permanently open access under the terms of the Creative Commons Attribution
License 4.0 International License
Faurschou and Wulf, 2007).
UVB radiation causes both erythema as
photocarcinogenesis. Photocarcinogenesis occurs mainly
due to their direct interaction with the cell DNA and
subsequent formation of dimers cyclobutane pyrimidine
and glycols thymine. However, there are several reasons
why the investigation of UVA role is also relevant. The
major consequence of UVA radiation buildup is the
generation of reactive oxygen species (ROS) that can
also cause cancer due to generation of derivatives of
nitrogenous bases of oxidized DNA such as 8-
hidroxidesoxiguanosina as well as tumor suppressor
genes modified as p53 (Seité et al., 2000; Heinrich et al.,
2004; Vielhaber et al., 2006).
In aerobic organisms, oxidation processes occur as a
result of natural oxygen consumption. The oxygen is
typically found in its most stable form, although in certain
situations such as the use of tobacco or alcohol,
inflammatory processes, ionizing radiation and in
particular, exposure to UV radiation can produce these
reactive species, which are highly unstable and can do
skin damage through oxidation. Free radicals are
particularly harmful, because the presence of an unpaired
electron makes them highly unstable and gives them a
tendency to react with other molecules, making it stable
(Gálvez, 2010).
Over the past three decades, with the depletion of the
ozone layer, which has become a major environmental
problem, the special role of flavonoids in the short
wavelength absorption of UVB solar radiation has been
strongly emphasized (Rozema et al., 1997; Burchard et
al., 2000).
The use of botanical agents to reduce the occurrence
of skin cancer by photochemoprotection has increasingly
gained attention. Photochemoprotection is the term that
defines the use of agents capable of ameliorating the
adverse effects of ultraviolet radiation on the skin, and
much has been appreciated as a viable way of reducing
the occurrence of skin cancer (F'guyer et al., 2003).
Studies show that this type of prevention is required in
daily life to avoid serious damage (Wu et al., 2011). In
recent years the use of agents, especially botanical
antioxidants, present in the common diet and in
beverages consumed by the population has received
considerable attention as photochemoprotection agents
for human use. Many of these agents have found a place
in skin care products (Afaq et al., 2005).
One of the trends of the market and of Cosmetic
Science is the development of products with a greater
number of components of natural origin, especially those
of vegetal origin, rationally exploiting biodiversity (Biavatti
et al., 2007). This is seen with great interest by the
international market, especially if the material presents
scientific studies proving the safety and efficacy, besides
the commitment with the sustainable development
(Franquilino, 2006).
There is a structural analogy between the synthetic
Filho et al. 849
sunscreens and the active ingredients of natural products
that present a protective action in the skin, since the
ultraviolet absorption has been verified when using
vegetal extract in pharmaceuticals and cosmetics
(Ramos et al., 1996). In this way, sunscreens are
substances capable of absorbing, reflecting or refracting
ultraviolet radiation and thus protect the skin from direct
exposure to sunlight (Giokas et al., 2005).
Flavonoids have shown several functions in
photoprotection routes (Agati and Tattini, 2010). This is
consistent with the flavonoid location in a wide range of
plant organs, and different cells and cell compartments
(Agati et al., 2012). These molecules have been
recognized to perform various functions in higher plants
responses in several environmental constraints (Winkel-
Shirley, 2002; Roberts and Paul, 2006).
Promising photoprotective activity of plant extracts from
Brazilian Caatinga Biome has been reported, such as
Neoglaziovia variegata (Oliveira-Junior et al., 2015),
Triplaris gardneriana (Macedo et al., 2015) and
Alternanthera brasiliana (Silva et al., 2014), and its
activity was associated to the phenolic compounds as
flavonoids. Thus, it was decided to carry out this
systematic review, where articles that related flavonoid
with photoprotective activity were researched and
analyzed.
METHODS
This systematic review was carried out through a literature search
performed in January 2016 and included articles published over a
period of 10 years (January 2006 to January 2016). This literature
search was performed through specialized search databases
(PubMed, Scopus and Science Direct) using several combinations
of the following keywords: flavonoid, photoprotection and
sunscreen. The manuscript selection was based on the inclusion
criteria: articles published in English and articles with keywords in
the title, abstract or full-text. 446 articles were identified: 83 from
PubMed, 67 from Scopus and 296 from Science Direct. However,
42 papers were indexed in two or more databases and were
considered only once, resulting in 404 articles. Out of this total, 22
articles were selected as the others did not meet the inclusion
criteria.
For the selection of the manuscripts, three investigators first
selected the articles according to title, then to abstract and then
through an analysis of the full-text publication. Any disagreement
was resolved through a consensus between the investigators. The
resulting articles were manually reviewed with the goal of identifying
and excluding the studies that did not fit the criteria described
above.
RESULTS AND DISCUSSION
Selection of articles
The primary search identified 446 articles, with 83 from
PubMed, 67 from Scopus and 296 from Science Direct.
However, out of this total, 42 were indexed in two or more
databases and were considered only once, resulting in
850 J. Med. Plants Res.
Figure 1. Flowchart of included studies.
404 articles. After initial screening of the titles, abstracts
or keywords, 22 articles were selected as the others did
not meet the inclusion criteria (n= 382) or referred to
studies with flavonoids and photoprotection. A flowchart
illustrating the progressive study selection is shown in
Figure 1.
Flavonoids with photoprotective activity
Table 1 shows the chemical structures, SPF-UVB, PF-
studies with
polyphenols.
Rutin
Rutin, also called rutoside and quercetin-3-O--
rutinoside, is a glycoside flavonoid of quercetin and
-L-rhamnopyranosyl---D-
glucopyranose) (Lucci et al., 2009).
The sun protection factor UVB (SPF-UVB) and
protection factor UVA (PF-UVA) were verified by several
authors, both in pharmaceutical formulations containing
only rutin as principle active ingredient as in association
with other photoprotective agents using a transmittance
method proposed by Diffey et al. (1989). Rutin
formulations presented SPF-UVB 4.72 ± 0.20 and FP-
UVA 4.92 ± 0.20. When associated to physical filters
such as titanium dioxide (TiO2) and zinc oxide (ZnO),
rutin showed an increase in the protective factor.
Formulations in the presence of rutin with TiO2, the SPF-
UVB were 34.29 ± 8.31, and PF-UVA 16.25 ± 2.71. For
formulations in the presence of rutin with ZnO, SPF-UVB
was 11.25 ± 3.31, and the PF-UVA 9.75 ± 2.81. The
authors considered that rutin act synergistically with TiO2
because there was a significant increase in the SPF-UVB
and PF-UVA values when associated. However, the
authors have considered the effect of rutin with ZnO only
an additive effect, because the increase was not
considered as significant. Also, it was found that
formulations containing rutin were photostable, varying
less than 10% the value of SPF-UVB and PF-UVA after 2
h of irradiation under controlled conditions (Choquenet et
al., 2008).
In another study, researchers found that rutin
incorporated in cosmetic photoprotective formulations
have presented biocompatibility with human skin. Rutin
formulations showed high antioxidant potential, with
increase of 75% to radical scavenging activity compared
to formulations containing only synthetic filters used
(ethylhexyl methoxycinnamate 3.75 and 7.5%, ethylhexyl
salicylate 2.5 and 5.0%, ethylhexyl dimethyl PABA 4.0
and 8.0%, octocrylene 5.0 and 10.0%). Rutin was
incorporated in a fixed concentration of 0.1%.
Furthermore, the synthetic filters and rutin association
significantly increased critical wavelength of the
Filho et al. 851
Table 1. Chemical structure, SPF-UVB, PF-UVA,
Molecule
name
Chemical structure
SPF-UVB and/or PF-
UVA
UVA/UVB
ratio and/or λc
In vitro and/or in vivo
studies
References
Rutin
O
O
O
OH OH
OH
O
OH
OH
OH
OH O
O
OH OH OH
CH3
SPF-UVB by Diffey et
al. (1989) method (in
formulation) = 4.72 ±
0.20
PF-UVA by Diffey et al.
(1989) method (in
formulation) = 4.92 ±
0.20
-
In vitro: association with
synthetic filters in
formulations to check
SPF-UVB and PF-UVA
by a spectral
transmittance method;
formulations with
nanostructured lipid
carriers; formulations
with gelatin
nanoparticles.
Choquenet et
al., 2008;
Peres et al.,
2015;
Oliveira et al.,
2015;
Oliveira et al.,
2016;
Kamel et al.,
2015;
Quercetin
O
O
OH
OH OH
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
10.3
SPF-UVB using the
method proposed by
Diffey et al. (1989) in
formulation = 4.52 ±
0.38
PF-UVA using the
method proposed by
Diffey et al. (1989) in
formulation = 5.77 ±
0.55
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.93
c by Diffey
(1994) method
= 385 nm
In vitro: association with
synthetic filters in
formulations to check
SPF-UVB and PF-UVA
by a spectral
transmittance method;
antioxidant activity;
tests with dermal
fibroblasts irradiated
with UVA; tests with
inflammatory cytokines
(IL-1, IL-6, IL-8 and
TNF-); tests NF-B,
p53 e p50 modulation.
Stevanato et al.,
2014;
Choquenet et
al., 2008;
Evans-Johnson
et al., 2013;
Vicentini et al.,
2011.
Crisin
O
O
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
18.6
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.6
c by Diffey
(1994) method
= 380 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c.
In vivo: damage to
keratinocytes induced
by UVB.
Stevanato et al.,
2014;
Gregoris et al.,
2011;
Wu et al., 2011.
852 J. Med. Plants Res.
Table 1.
Epigallocatechi
n-3-gallate
O
OH
OH
O
OH
OH
OH
OH
OH
OOH
-
-
In vitro:
immunosuppression
tests; UVB-induced
photocarcinogenesis;
formation of
cyclobutane pyrimidine
dimers; stabilizing
formulations containing
other antioxidants and
synthetic filters.
Meeran et al.,
2006;
Scalia et al.,
2013;
Bianchi et al.,
2011.
Luteolin
O
O
OH
OH
OH
OH
-
c by Diffey
(1994) method
= 370 nm
In vitro: tests with UVB-
irradiated keratinocytes;
antioxidant and anti-
inflammatory;
combination with
synthetic antioxidants.
In vivo: formation of
pyrimidine cyclobutane
dimers.
Wölfle et al.,
2011;
Wölfle et al.,
2013.
Genistein
O
O
OH
OH
OH
-
-
In vitro: photoprotection
in pigskin; model of
erythema and burns by
UV.
Lin et al., 2008;
Filho et al. 853
Table 1.
Equol
O
OH
OH
-
-
In vitro: photoprotection
in pigskin; model of
erythema and burns by
UV.
In vivo:
photoimunoprotection
against UV.
Lin et al., 2008;
Widyarini et al.,
2006.
Daidzein
O
O
OH
OH
-
-
In vitro: photoprotection
in pigskin; model of
erythema and burns by
UV.
Lin et al., 2008.
Biochanin A
O
O
OH
OCH3
OH
-
-
In vitro: photoprotection
in pigskin; model of
erythema and burns by
UV.
Lin et al., 2008.
Formononetin
O
O
OH
OCH3
-
-
In vitro: photoprotection
in pigskin; model of
erythema and burns by
UV.
Lin et al., 2008.
854 J. Med. Plants Res.
Table 1
Apigenin
O
O
OH
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
28.8
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.66
c by Diffey
(1994) method
= 380 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al.,
2014;
Gregoris et al.,
2011
Kaempferol
O
O
OH
OH
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
24.9
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.76
c by Diffey
(1994) method
= 385 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al.,
2014;
Gregoris et al.,
2011.
Catechin
O
OH
OH
OH OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
7.3
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.62
c by Diffey
(1994) method
= 385 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014;
Gregoris et al.,
2011.
Galangin
O
O
OH
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
16.2
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.71
c by Diffey
(1994) method
= 385 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014;
Gregoris et al.,
2011.
Filho et al. 855
Table 1
Naringenin
O
O
OH
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
12.3
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.54
c by Diffey
(1994) method
= 380 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014;
Gregoris et al.,
2011.
Pinocembrin
O
O
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
16.0
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.48
c by Diffey
(1994) method
= 380 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al.,
2014;
Gregoris et al.,
2011.
Epicatechin
O
OH
OH
OH
OH
OH
-
-
In vivo: minimal
erythemal dose model;
blood flow, density,
hydration and elasticity
of skin; measurement of
plasma concentration.
Heinrich et al.,
2006;
Williams et al.,
2009;
Mogollon et al.,
2014.
Coumaric
acid
OH
O
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
9.3
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.17
c by Diffey
(1994) method
= 335 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014.
856 J. Med. Plants Res.
Table 1.
Ferulic acid
OH
O
OH
O
CH3
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
11.9
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.27
c by Diffey
(1994) method
= 345 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014.
Caffeic acid
OH
O
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
28.0
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.43
c by Diffey
(1994) method
= 365 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014.
Caffeic acid
phenylethyl
ester
O
O
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
15.8
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.52
c by Diffey
(1994) method
= 370 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014.
Dimethyl
caffeic acid
OH
O
O
CH3
O
CH3
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
16.6
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.52
c by Diffey
(1994) method
= 370 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014.
Filho et al. 857
Table 1. .
Resveratrol
OH
OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
19.2
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.28
c by Diffey
(1994) method
= 340 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014.
Piceid
O
OH
OH
O
OH
OH OH
OH
SPF-UVB by Diffey et
al. (1989) method
(isolated flavonoid) =
9.9
UVA/UVB ratio
by Boots the
Chemist Ltd.
(1991) method
= 0.31
c by Diffey
(1994) method
= 345 nm
In vitro: SPF-UVB,
UVA/UVB ratio and c;
antioxidant activity.
Stevanato et al,
2014.
formulations, by a spectral transmittance method,
showing improved photoprotection, especially in
UVA region, which supports the use of this
flavonoid as adjuvant formulations (Peres et al.,
2015).
Rutin association with different other filters such
as benzophenone-3 (BF-3) and butyl
methoxydibenzoylmethane (BMDBM), resulted in
different profiles interaction. In general, rutin
provides antioxidant properties to the samples,
and all the formulations were considered safe for
human use, with good skin compatibility.
Surprisingly, the combination of rutin 0.1% and
BF-3 6.0% caused a SPF increase from 24.3 ±
1.53 to 33.3 ± 2.89, showing synergistic effect of
the flavonoid in this association, by Colipa
Guidelines method (2011). However, the same
result were not observed for the combination of
rutin and BMDBM, because there was a decrease
in the SPF value. However, the critical wavelength
values obtained were consistent with the BBM
profile, indicating that rutin was not effective when
coupled with this UVA filter, but did not affect the
filter absorption (Oliveira et al., 2015).
The encapsulation of natural products such as
rutin can offer improvements in the effectiveness
of sunscreen. This approach can provide
enhanced flavonoid content and a bioactive
compound produces improved with new functional
and physical characteristics (Oliveira et al., 2016).
Studies aimed at creating formulations with
nanostructured lipid carriers were performed with
rutin. A lipid based formulation Apifil® and rutin
(2%) reached the highest occlusive effect,
achieved higher encapsulation efficiency (96.96%
± 6.58) and release of flavonoid (82.23% ± 5.48)
in addition to the higher sun protection factor (2.72
± 0.20). Furthermore, different TiO2
concentrations were added to this formulation to
increase the SPF-UVB. The formulation
containing 5% TiO2 reached the highest value of
SPF-UVB (5.33 ± 0.20), larger area on the UV
absorption curve and critical wavelength above
370 nm, which demonstrated its high efficiency as
wavelength below which lies 90% of the area
under the absorbance curve. A higher critical
wavelength guarantees more UV protection,
especially protection from the rays with longer
wavelengths (UVA) (Kamel et al., 2015).
As an alternative to common synthetic
sunscreens, gelatin nanoparticles with rutin
encapsulated were formulated and associated
with ethylhexyl dimethyl PABA (EHDP), ethylhexyl
858 J. Med. Plants Res.
Methoxycinnamate (EHMC) and butyl
methoxydibenzoylmethane (BMDBM) in sunscreen
formulations. Gelatin nanoparticles with rutin promoted
an increasing of antioxidant activity by 74% in relation to
the free rutin. Furthermore, there was an increase in
SPF-UVB of 48%, by Colipa Guidelines method (2011),
indicating again the potential of natural sunscreens
(Oliveira et al., 2016).
Quercetin
In the study with quercetin (3,3',4',5,7-
pentahidroxyflavone), it was observed that this flavonoid
has absorption in both UVA and UVB regions, and its
further absorption into the UVA region. The SPF-UVB
checked was 10.3, by Diffey et al. (1989) method. The
Because there is not agreement upon a method to
measure the protection against UVA, the UVA/UVB ratio
(Boots The Chemist Ltd, 1991) and the critical
predictive values of absorption in the UV region. The
closer to 1 the value of the UVA/UVB ratio, the greater
the predictive value for absorption in UVA region, in the
s
spectrum in the UVA region (Stevanato et al., 2014).
The SPF-UVB and PF-UVA of quercetin were verified
in both formulations containing only the flavonoid as an
active principle ingredient as in association with other
filters using a transmittance method proposed by Diffey et
al. (1989). Quercetin presented SPF-UVB formulations of
4.52 ± 0.38 and FP-UVA 5.77 ± 0.55. Furthermore, the
prepared formulations were photostable, with
modification least 10% of SPF-UVB and PF-UVA after 2
h of controlled irradiation. In the same study, quercetin
showed an increase in protection when associated with
physical filters TiO2 and ZnO. For ZnO, the displayed
SPF-UVB was 29.70 ± 4.96, and PF-UVA 16.42 ± 1.67,
which configures a synergistic effect compared with the
effect of quercetin alone. For the zinc oxide SPF-UVB
was 9.97 ± 1.61, and PF-UVA 10.28 ± 1.63 showing a
purely additive effect compared to the effect of quercetin
alone (Choquenet et al., 2008).
Evans-Johnson et al. (2013) found that topical
application of a mixture of polyphenols derived from
almonds (isorhamnetin, catechin, epicatechin, kaempferol
and quercetin) in which quercetin was in higher
concentration than the others, significantly attenuates
apoptosis induced by UVA radiation in dermal fibroblasts,
keeping the skin morphology healthy as well as cell
differentiation, and tends to decrease the reducing
keratinocyte proliferation induced by UVA. The
mechanisms of action was not elucidated in this study,
however, the authors suggest that potential mechanisms
may include absorbance of UV radiation, elimination of
free radicals generated from this radiation, and
modulation of cell signaling and endogenous antioxidant
defenses.
Inflammatory cytokines, such as IL- -6, IL-8 and
TNF- -
induced inflammation and skin damage (Cho et al.,
2003). Thus, the effects of quercetin on expression of
inflammatory cytokines induced by UV irradiation in
primary human keratinocytes were investigated. The
pretreatment of keratinocytes in culture with different
concentrations of quercetin (2, 6 and 20 µg/ml) resulted
in a concentration-dependent inhibition of UV (50
mJ/cm2) irradiation-induced IL- n.
Maximum inhibition (80%) was observed in 20 µg/ml of
quercetin. Therefore, in subsequent experiments, 20
µg/ml of quercetin was used to pretreat keratinocytes
before they were subjected to UV irradiation. UV
irradiation induced marked increase of IL- , IL-6, IL-8
and TNF- -dependent
manner. Pretreatment with quercetin suppressed the
induction of all four cytokines: IL- -6 (80%),
IL-8 (76%) and TNF-
Since nuclear factor kappa B (NF-B) pathway plays an
essential role in induction of inflammatory cytokines
expression by UV irradiation, quercetin ability to inhibit
the activation of NF- was analyzed by UV irradiation.
UV irradiation of primary human keratinocytes enhanced
NF- tion by approximately 5-fold. Quercetin
pretreatment inhibited UV irradiation-induced NF-
binding activity by approximately 80%. In addition, protein
levels of p65, NF-
treatment with quercetin. Thus, it is believed that the
ability of quercetin to reduce the inflammatory action
induced by UV irradiation is mediated, at least in part, by
their inhibitory effects on the activation of NF-
inflammatory cytokine production (Vicentini et al., 2011).
The in vitro results cannot always be correlated with in
vivo results, and generally high SPF values are required
in vitro to achieve median or lower values in vivo. The
biological medium is too complex for the flavonoid easily
achieve high activity, because several factors may be
related to this reduction in efficacy, such as the area of
application, the amount of formulation used, the
individual's skin and its integrity or even the components
of the formulation.
Chrysin
Chrysin (5,7-dihidroxiflavon), a natural flavonoid
occurring in various plants and foods such as honey and
propolis, reportedly opposes inflammation and
carcinogenesis, but has rarely been applied in skin care
products (Wu et al., 2011). In a study with isolated
chrysin, it was found that this flavonoid presents
absorption spectrum in both regions (UVA and UVB). The
checked SPF-UVB by Diffey et al. (1989) method was
18.6. The UVA/UVB ratio was found to be 0.6, and
380 nm (Stevanato et al., 2014). To achieve SPF-UVB of
20, it was found that the concentration of chrysin (w/v) in
solution should be about 7.5% (Gregoris et al., 2011).
Studies with animals have shown that topical
application of chrysin was very efficient in percutaneous
absorption, with no skin irritation. The same study found
the effect of chrysin protect against damage to
keratinocytes induced by UV radiation. The results
showed that chrysin was able to reduce apoptosis, as
well as the production of reactive oxygen species and the
expression of the enzyme cyclooxygenase-2 (COX-2)
induced by UVA and UVB radiation. COX-2 is an enzyme
that participates of inflammatory processes which cleaves
membrane lipids in the presence of oxygen and produces
chemical mediators of inflammation such as prostanoids
(Wu et al., 2011).
Epigallocatechin-3-gallate
Green tea is produced from fresh leaves of Camellia
sinensis plant species (Yang and Wang, 1993). The
leaves undergo fermentation process, preventing
oxidation and polymerization of polyphenols contained in
the plant. This tea contains four main polyphenols: ()-
epicatechin (EC), ()-epicatechin-3-gallate (ECG), ()-
epigallocatechin (EGC) and ()-epigallocatechin-3-gallate
(EGCG), the latter being in a higher concentration,
reaching 50% of total catechins (Yusuf et al., 2007).
The first evidence that green tea polyphenols may have
a protective role in UV-induced skin cancer was
suggested by a study conducted by Wang et al. (1991)
who showed that green tea served in water (orally) to
mice, exhibited a prolonged dose-dependently in tumor
development time when they were subjected to a photo-
carcinogenesis protocol. Similar observations were noted
in relation to topical application of green tea polyphenols
(Wang et al., 1991).
EGCG prevent UVB-induced immunosuppression by
inducing interleukin-12 (IL-12). Because the
immunosuppression is a risk factor for
photocarcinogenesis, the possibility that EGCG also
prevents UVB-induced photocarcinogenesis through a
DNA repair mechanism, dependent on IL-12 was
investigated. To investigate this possibility, it was
determined the effects of EGCG on photocarcinogenesis
in IL-12 KO mice using the formation of cyclobutane
pyrimidine dimers (CPDs) as an extension indicator of
DNA damage induced by UVB. Topical application of
EGCG (1 mg/cm2 skin) prevented photocarcinogenesis in
wild-type (C3H/HeN) mice in terms of tumor incidence
and tumor multiplicity did but not prevent
photocarcinogenesis IL-12 KO mice. DNA damage, as
determined by the formation of CPDs and the number of
sunburn cells, were reduced faster in wild-type mice skin
treated with EGCG than the untreated control mice. In
contrast, the extent of UVB-induced DNA damage and
Filho et al. 859
the numbers of sunburn cells were not significantly
different in the EGCG-treated IL-12 KO mice and
untreated control group (Meeran et al., 2006).
In addition, treatment of XPA-proficient human
fibroblast cells with EGCG promoted repair of UVB-
induced CPDs in a dose-dependent manner but not in an
XPA-deficient cells, indicating that the nucleotide excision
repair mechanism is involved in EGCG-mediated DNA
repair. Taken together, these results indicate EGCG can
prevent photocarcinogenesis through an EGCG-induced
IL-12dependent DNA repair mechanism (Meeran et al.,
2006).
EGCG has a high sunscreen activity; however, this
catechin is highly unstable under sunlight. Thus, it was
found EGCG behavior in formulations with various co-
antioxidants such as vitamin E, butylated hydroxytoluene
(BHT), vitamin -lipoic acid for their potential to
protect the EGCG from photochemical degradation. The
-lipoic acid in the formulation
significantly reduced the decomposition of EGCG light-
induced from 76.9 ± 4.6 to 20.4 ± 2.7%, and from 12.6 ±
1.6%, respectively. Moreover, BHT had no effect,
showing loss of 78.1 ± 4.6% EGCG, and vitamin E
increased the EGCG photolysis to 84.5 ± 3.4%. The
functional stability of EGCG in the formulations exposed
to the solar simulator was evaluated by measuring the
antioxidant activity in vitro. After irradiation, the reduction
in the antioxidant capacity of the formulation with EGCG
was lower (21.8%) than degradation of extension
(76.9%), suggesting the formation of photoproducts with
antioxidant properties. Among the evaluated antioxidants,
-lipoic acid showed the most positive results, proving to
be an effective antioxidant co-agent for stabilization of the
()-epigallocatechin-3-gallate in dermatological products
for photoprotection of the skin because it reduced most
significantly the degradation of EGCG and stabilized
better antioxidant activity of the formulation, down only
1.4% of the activity (Scalia et al., 2013).
Another attempt to stabilize EGCG formulations was
performed, this time with commercial filters BMDBM,
ethylhexyl methoxycinnamate (EMC), benzophenone-4
(BP-4) and Tinosorb M results compared with the control
formulation (without adjuvants filters) showed a small
(11.5%) but significant reduction in the photodegradation
of EGCG, which was achieved by UVB-filter EMC while
the UVA-filter BMDBM was ineffective. In the presence of
BP-4, a more marked decrease in the light-induced
decomposition of EGCG was obtained (51.6 ± 2.7%)
compared to EMC. Tinosorb M produced stabilizing effect
comparable to that of BP-4, indicating that the
photosensitivity of EGCG is mainly caused by
wavelengths in the UVB region (Bianchi et al., 2011).
Luteolin
The flavonoid luteolin or luteol is a polyphenol with potent
860 J. Med. Plants Res.
antioxidant activity. The antioxidant and photoprotective
properties of luteolin were investigated in human
keratinocytes in vitro, ex vivo and in vivo. The
spectroscopy revealed maximum absorptions of luteolin
in the UVB region as both the UVA region, and less than
10% absorption was below 370 n
remained above this wavelength. In human skin, luteolin
effectively reduced the formation of CPDs induced by
UVB. The antioxidant activity was evaluated in several
trials with means and using cell-free media cells. In
DPPH radical scavenge assay, the effective
concentration to achieve 50% of maximal effect (EC50) of
luteolin was 12 µg/ml, comparable to Trolox (25 µg/ml)
and N-acetylcysteine (32 µg/ml), drugs used as positive
control in the assay. In contrast, in CM-H2DCFDA assay
performed with UVB-irradiated keratinocytes, luteolin was
much more effective (EC50 3 µg/ml) compared to Trolox
(EC50 of 12 µg/ml) and N-acetylcysteine (EC50 847
µg/ml). Luteolin also inhibit both the skin erythema
induced by UVB, the upregulation of cyclooxygenase-2
and prostaglandin E2 production in human skin via
interfering with the MAPK pathway. These data suggest
that luteolin may protect human skin against UVB
damage by a combination of UV-absorbing, DNA-
protection, antioxidant activity and anti-inflammatory
properties (Wölfle et al., 2011).
Another study found that the addition of ubiquinone and
tocopherol increase antioxidant activity and
photoprotection luteolin. The combination of luteolin with
ubiquinone and tocopherol in a ratio of 4:4:1 gave the
highest antioxidant efficacy than the equivalent
concentration of any of isolated individual antioxidants.
Luteolin greatly reduced the formation of 2',7'-
dichlorofluorescein by reactive oxygen species in a
concentration dependent manner, from 2 mg/ml.
Ubiquinone and tocopherol were not effective at
concentrations between 0 and 4 µg/ml. However, when
combined antioxidants, already at 0.25 mg/ml was
sufficient to completely neutralize the formation of ROS
induced by irradiation. In addition, the antioxidants
combined present sunscreens effects, and at
concentration of 2 mg/ml the combination was able to
completely protect cells against damage induced by UV.
Luteolin alone showed only partial photoprotective effect
at 2 mg/ml. Tocopherol and ubiquinone showed no
photoprotective effect when isolated (Wölfle et al., 2013).
The combination of luteolin with tocopherol and
ubiquinone is quite effective, because each antioxidant
has a different activity profile. Tocopherol is the
predominant antioxidant as physiological barrier to
human skin, which protects cell membranes and the
stratum corneum (Thiele et al., 2001). Ubiquinone is part
of the electron transport chain responsible for energy
production in every cell. Furthermore, the anti-apoptotic
and mitochondria protective properties of ubiquinone
have been described (Papucci et al., 2003). The
association luteolin-tocopherol-ubiquinone combines the
activities of ultraviolet absorption and DNA protection of
luteolin, with stratum corneum protection of tocopherol
and mitochondrial protection of ubiquinone. In summary,
the findings suggest that the potent antioxidant effects
and sunscreens such as flavonoids luteolin can be
enhanced by addition of low concentrations of other
antioxidants (Wölfle et al., 2013).
Isoflavonoids (genistein, equol, daidzein, biochanin A
and formononetin)
Isoflavones are a major group of phytoestrogens from
plants, with chemical characteristic of polyphenolic and
non-steroidal nature, presenting biological action similar
to estrogen (Lin et al., 2008).
For genistein, it was demonstrated its action in rat skin
protection against the oxidative stress, photodamage and
carcinogenesis induced by UVB (Wei et al., 2002;
Shyong et al., 2002). The topical administration of equol
effectively reduced the incidence of cancers induced by
chronic exposure to UV radiation, and UVA-induced lipid
peroxidation in mouse skin (Widyarini et al., 2005).
Administration of topical solutions containing 0.5% of
the isoflavones genistein, daidzein, biochanin A and
formononetin was able to exert photoprotective effect on
pig skin, reducing the number of sunburn cells by UV
radiation and/or erythema. Genistein, daidzein and
biochanin A were more significant as photoprotective.
The formononetin showed no effect in the prevention of
burns, however, proved to be very effective in reducing
erythema. Individual differences between percutaneous
absorption of various isoflavones may be responsible for
the difference of efficacy in protection revealed in the
study. It is also likely that the pharmacodynamics of the
isoflavones may be different. For example, genistein
inhibits the activity of tyrosine kinase receptor, and can
thereby reduce damage caused by UV radiation better
than isoflavones which do not inhibit the activity of this
receptor (Lin et al., 2008).
Equol, other isoflavonoid, was also able to significantly
reduce pork skin erythema, however with less activity
than the others isoflavones mentioned (Lin et al., 2008).
Another study showed that the photoimunoprotection of
isoflavonoids can result from interaction with a natural
skin antioxidant, known to modulate photodamage
induced by UV, the metallothionein (MT). In rats with a
mutation that inhibits the expression of two subtypes of
MT (I and II), it was noticed that the immune protection of
equol against simulated solar radiation of UV was
revoked. Equol administered in solution topically (10 µM)
did not enable the MT expression in the normal mouse
skin, but increases MT expression in the epidermis of the
animal after UV irradiation, demonstrating the
dependence photoimmunoprotection of equol on
induction of MT, as evidenced by immunohistochemistry
tests performed. Interestingly, equol incorporated in lotion
did not affect the MT expression in mice and also showed
no immunomodulatory effect. The data for the tests with
equol are consistent with the hypothesis that the
photoprotection is dependent of the level of skin MT
expression. This suggests that these isoflavonoid act as
exogenous antioxidants interacting with endogenous
cellular antioxidant activity of the skin (Widyarini et al.,
2006).
It is unclear how isoflavonoids can stimulate MT when
the cells are exposed to radiation. Some studies report
that the regulation of MT gene may involve metals,
steroid hormones, redox molecules and various cytokines
(Sciavolino and Vilcek, 1995; Nishimura et al., 2000;
Ablett et al., 2003).
Apigenin, kaempferol, catechin, galangine,
naringenin and pinocembrine
Flavonoids are important dietary components, and
consequently these molecules and their metabolites
rarely cause sensitization. From this, studies have
verified the possibility of using these compounds in
photoprotective formulations, correlating the antioxidant
power with its sun protection capacity (Stevanato et al.,
2014).
Among the flavonoids mentioned above (apigenin,
kaempferol, catechin, galangine, naringenin and
pinocembrine), UV spectra showed that kaempferol and
galangine are characterized by absorptions at
wavelengths relatively higher than the others. The
absorbance spectra of these two flavonoids revealed
absorption peak between 360 (galangine) and 365 nm
(kaempferol). Apigenin obtained its maximum absorption
at 330 nm, catechin at 290 nm, naringenin and
pinocembrine at 290 nm. Regarding the SPF-UVB by
Diffey et al. (1989) method, the UVA/UVB ratio and
Kaempferol (24.9
U
photoprotection data, it was verified the antioxidant
capacity against lipid peroxidation of these flavonoids.
Kaempferol, catechin and galangine presented lower IC50
values (in mM), 2.0 ± 0.2, 2.0 ± 0.2 and 3.0 ± 0.3,
respectively. The others showed IC50 values above 50
µM (84 ± 8 for apigenin, 56 ± 5 for naringenin and 110 ±
10 for pinocembrine (Stevanato et al., 2014; Gregoris et
al., 2011). Thus, a formulation with kaempferol, apigenin
and galangine could confer a broad spectrum of
protection in the UVA and UVB regions and confer high
levels of antioxidant activity for the skin.
Isolated flavonoids generally do not give good SPF
values, therefore, studies in the cosmetic field should
Filho et al. 861
always be conducted in the sense of associating these
polyphenols with synthetic filters to try to reduce their
concentrations from different combinations among them.
Even if the in vivo values of SPF are high, when added in
cosmetic formulations these values tend to reduce due to
dilution of the flavonoid in the formula, or loss of stability
of this formulation may still occur. Using the flavonoid
alone to provide photoprotection is apparently not an
advantageous option.
Flavanol cocoa (catechin and epicatechin)
Antioxidants present in diet may contribute to the
photoprotection and are important to maintain skin health.
Was investigated the influence of 12 weeks of chocolate
consumption with high flavanol content in skin sensitivity
to UV radiation, measured by minimal erythemal dose
(MED). Two groups of women have used a high dose of
flavanols (HF) (326 mg) or low dose of flavanols (LF) (27
mg) in the form of cocoa powder dissolved in 100 ml of
water for 12 weeks. Epicatechin and catechin were
flavanols used in smaller or larger amounts. The
photochemoprotection and indicators of the skin condition
were analyzed before and during the intervention. After
selected areas of skin exposure, the radiation MED
obtained from a solar simulator was calculated. The UV-
induced erythema was significantly reduced in the HF
group in 15 and 25%, after 6 and 12 weeks, respectively,
while no change occurred in LF group. The ingestion of
high flavanol dose led to an increase in blood flow of skin
and subcutaneous tissue, increased density, and skin
hydration. Skin thickness was increased and the
transepidermal water loss was reduced in the HF group,
although neither of these variables were modified in LF
group. The evaluation of the surface of the skin showed
significant reduction in roughness and scaling the HF
group compared with the LF group at 12 weeks. Thus, it
was concluded that cocoa flavanols contribute to the
endogenous photochemoprotection, improve blood
circulation and affect dermal surface of the skin variables,
as well as the hydration (Heinrich et al., 2006).
Another study was conducted with 30 healthy subjects
to verify similar results. Two groups of fifteen persons
each were randomly assigned to start HF or LF diet.
Each one consumed a 20 g portion of chocolate suitable
daily, with or without high dose of flavanols. The MED
was assessed at baseline and after 12 weeks under
standard conditions. In the HF group, MED the average
more than doubled after 12 weeks of chocolate
consumption, while in LF group DEM remained without
significant change, demonstrating, again, that regular
consumption of a rich chocolate flavonoids provides
photochemoprotection significant and may be effective in
protecting human skin from the harmful effects of UV
radiation (Williams et al., 2009).
Another study investigated the effect of 12 weeks of
862 J. Med. Plants Res.
chocolate consumption with high flavanol content in skin
sensitivity to UV radiation, measured by MED, as well as
the elasticity and skin hydration. The study only used
women, aged 20 to 65 years. Two groups were formed:
One received daily 30 g of chocolate with an HF and the
other group received the same amount, but a chocolate
with LF. DEM was assessed at baseline and at 6, 9, 12
and 15 weeks (three weeks after the daily consumption).
The curious fact is that in this new study, from initial time
to 12 weeks of time, the results for both groups showed
no significant differences for the MED, unlike the study
cited above. Age over 50 years was associated with
major changes in the MED, within the same group in 15
weeks. Both the elasticity and skin hydration increased
by six weeks in the HF group compared to the LF group.
Plasma concentrations of polyphenols were similar in
both groups at baseline. LF group showed a small
increase, but statistically significant, compared
epicatechin dosage in plasma at weeks 6, 9 and 12
compared to baseline. The HF Group was marked by
more considerable increases of epicatechin in plasma
(Mogollon et al., 2014).
Other polyphenols with photoprotective activity
Hydroxycinnamic acid derivatives (coumaric acid,
ferulic acid, caffeic acid, caffeic acid phenylethyl
ester and dimethyl caffeic acid)
Compounds derived from hydroxycinnamic acid and its
homologues and/or derivatives, found in fruits,
vegetables, coffee and wine, are considered good
candidates to provide photoprotection due to their
chemical structures. SPF-UVB by Diffey et al. (1989)
method, UVA/UVB ratio and critical wavelength were
evaluated for each of these compounds. The results
nm); caffeic acid phenylethyl ester (15.8 SPF, UVA/UVB
thyl caffeic acid (16.6 SPF,
caffeic acid showed better SPF-UVB (28.0), followed by
dimethyl caffeic acid (16.6). Best UVA/UVB ratio and
better critical wavelengths were checked for caffeic acid
phenylethyl ester and dimethyl caffeic acid (0.52 and 370
nm for both) (Stevanato et al., 2014). Thus, a formulation
containing a mixture of caffeic acid with caffeic acid
phenylethyl ester, or dimethyl caffeic acid, could provide
significant protection values in both the UVA region as in
UVB.
Resveratrol and piceid
Long term studies have shown that topical application of
resveratrol (pre and post treatment) results in inhibition of
tumor incidence induced by UVB, and delay in the onset
of tumor of the skin (Baumann, 2009). However, Regev-
Shoshani et al. (2003) demonstrated that resveratrol is
susceptible to enzymatic oxidation while piceid, its
glycosylated form, it is sturdy and retains its antioxidant
capacity and beneficial biological properties. SPF-UVB by
Diffey et al. (1989) method, UVA/UVB ratio and critical
wavelength were evaluated for each of these stilbenes.
The results follow: Resveratrol (19.2 SPF, UVA/UVB 0.28
containing the two stilbene could confer good protection
in the UVB region, although not as effective in the UVA
region due their low UVA/UVB ratio values and low
critical wavelength.
Conclusions
In this systematic review, different mechanisms involved
in the photoprotective potential of flavonoids were
discussed. One of the main mechanisms of action is the
absorption of UV light, a fact directly related to the
conjugated double bonds in the molecule of flavonoids.
Another mechanism involved is the ability of flavonoids to
stabilize ROS, due to the presence of hydroxyl groups
attached to aromatic rings, especially (Stevanato et al.,
2014).
Over the past decade, much has been researched on
flavonoids as photoprotective agents. Not satisfied only
with SPF-UVB values, some researchers sought to
investigate by what mechanism the molecule exerts the
effect. However, the mechanisms of most flavonoids still
are not completely elucidated and remains unknown,
making this an active and attractive field for basic and
clinical research, leaving it as a perspective for the next
decade, that is, the realization of new types of studies
that exceed their activity in vitro to in vivo so that their
sun protection factor values are maintained.
Conflicts of Interests
The authors have not declared any conflict of interests.
REFERENCES
Ablett E, Whiteman DC, Boyle GM, Green AC, Parsons PG (2003).
Induction of metallothionein in human skin by routine exposure to
sunlight: evidence for a systemic response and enhanced induction
at certain body sites. J. Invest. Dermatol. 120:318-324.
Afaq F, Adhami VM, Mukhtar H (2005). Photochemoprevention of
ultraviolet B signaling and photocarcinogenesis. Mutat. Res. 571(1-
2):153-73.
Agati G, Azzarello E, Pollastri S, Tattini M (2012). Flavonoids as
antioxidants in plants: location and functional significance. Plant Sci.
196:67-76.
Agati G, Tattini M (2010). Multiple functional roles of flavonoids in
photoprotection. New Phytol. 186:786-793.
Baumann L (2009). Antioxidants. Cosmetic Dermatology: Principle and
Practice, second ed. McGraw Hill Professional Inc., New York.
Bianchi A, Marchetti N, Scali -
epigallocatechin-3-gallate in topical cream formulations and its
photostabilization. J. Pharm. Biomed. Anal. 56:692-697.
Biavatti M, Marensi V, Leite SN, Reis A (2007). Ethnopharmacognostic
survey on botanical compendia for potential cosmeceutic species
from Atlantic Forest. Rev. Bras. Farmacogn. 17:640-653.
Boots the Chemist Ltd (1991). The Guide to Practical Measurement of
UVA/UVB Ratios. The Boots Co. PLC, Nottingham, England.
Burchard P, Bilger W, Weissenböck G (2000). Contribution of
hydroxycinnamates and flavonoids to epidermal shielding of UV-A
and UV-B radiation in developing rye primary leaves as assessed by
ultraviolet-induced chlorophyll fluorescence measurements. Plant
Cell Environ. 23:1373-1380.
Cho SY, Park SJ, Kwon MJ, Jeong TS, Bok SH, Choi WY, Jeong WI,
Ryu SY, Do SH, Lee CS, Song JC, Jeong KS (2003). Quercetin
suppresses proinflammatory cytokines production through MAP
kinases and NF- -stimulated
macrophage. Mol. Cell. Biochem. 243:153-160.
Choquenet B, Couteau C, Paparis E, Coiffard LJM (2008). Quercetin
and rutin as potential sunscreen agents: determination of efficacy by
an in vitro method. J. Nat. Prod. 71(6):1117-1118.
Colipa Guidelines: The European Cosmetic Association (2011). In vitro
of sunscreen products. Brussels, p. 28.
Diffey BL (1994). A method for broad spectrum classification of
sunscreens. Int. J. Cosmet. Sci. 16:47-52.
Diffey BL, Robson J (1989). A new substrate to measure sunscreen
protection factors throughout the ultraviolet spectrum. J. Soc.
Cosmet. Chem. 40:127-133.
Evans-Johnson JA, Garlick JA, Johnson EJ, Wanga XD, Chen CYO
(2013). A pilot study of the photoprotective effect of almond
phytochemicals in a 3D human skin equivalent. J. Photochem.
Photobiol. B. 126:17-25.
Faurschou A, Wulf HC (2007). The relation between sun protection
factor and amount of sunscreen applied in vivo. Br. J. Dermatol.
156(4):716-719.
F'guyer S, Afaq F, Mukhtar H (2003). Photochemoprevention of skin
cancer by botanical agents. Photodermatol. Photoimmunol.
Photomed. 19(2):56-72.
Franquilino E (2006). In expansion. Cosmet. Toiletries 18:7-10.
Gálvez MV (2010). Antioxidants in Photoprotection: Do They Really
Work? Actas Dermosifiliogr. 101:197-200.
Gardiner J, Bailey P, Makino T, Heerink B (2006). Colipa guidelines:
International sun protection factor (SPF) Test method. Eur. Cosmet.
Assoc. 1:1-9.
Giokas DL, Sakkas VA, Albanis TA, Lampropoulou DA (2005).
Determination of UV-filter residues in bathing waters by liquid
chromatography UV-diode array and gas chromatography-mass
spectrometry after micelle mediated extraction-solvent back
extraction. J. Chromatogr. A. 1077:19-27.
Gregoris E, Fabrisa S, Bertelle M, Grassato L, Stevanato R (2011).
Propolis as potential cosmeceutical sunscreen agent for its combined
photoprotective and antioxidant properties. Int. J. Pharm. 405:97-101.
Heinrich U, Neukam K, Tronnier H, Sies H, Stahl W (2006). Long-term
ingestion of high flavanol cocoa provides photoprotection against UV-
induced erythema and improves skin condition in women. J. Nutr.
136:1565-9.
Heinrich U, Tronnier H, Kockott D, Kuckuk R, Heise HM (2004).
Comparison of sun protection factors determined by an in vivo and
different in vitro methodologies: a study with 58 different
commercially available sunscreen products. Int. J. Cosmetic Sci.
26:79-89.
Kamel R, Mostafa DM (2015). Rutin nanostructured lipid cosmeceutical
preparation with sun protective potential. J. Photochem. Photobiol. B.
153:59-66.
Lin JY, Tournas JA, Burch JA, Monteiro-Riviere NA, Zielinski J (2008).
Topical isoflavones provide effective photoprotection to skin.
Photodermatol. Photoimmunol. Photomed. 24:61-66.
Lucci N, Mazzafera P (2009). Rutin synthase in fava
Filho et al. 863
and influence of stressors. Can. J. Plant Sci. 89(05):895-902.
Macedo SKS, Almeida TS, Ferraz CAA, Oliveira AP, Anjos VHA,
Siqueira-Filho JA, Araújo ECC, Almeida JRGS, Silva NDS, Nunes XP
(2015). Identification of flavonol glycosides and in vitro
photoprotective and antioxidant activities of Triplaris gardneriana
Wedd. J. Med. Plants Res. 9(7):207-215.
Meeran SM, Mantena SK, Elmets CA, Katiyar SK (2006). (-)-
Epigallocatechin-3-gallate prevents photocarcinogenesis in mice
through interleukin-12-dependent DNA repair. Cancer Res. 66:5512-
5520.
Mogollon JA, Boivin C, Lemieux S, Blanchet C, Claveau J, Dodin S
(2014). Chocolate flavanols and skin photoprotection: a parallel,
double-blind, randomized clinical trial. Nutr. J. 13:1-12.
Nishimura N, Reeve VE, Nishimura H, Satoh M, Tohyama C (2000).
Cutaneous metallothionein induction by ultraviolet B irradiation in
interleukin-6 null mice. J. Invest. Dermatol. 114:343-8.
Oliveira CA, Peres DD, Graziola F, Chacra NAB, Araújo GLB, Flórido
AC, Mota J, Rosado C, Velasco MVR, Rodrigues LM, Fernandes AS,
Baby AR (2016). --
Eur. J. Pharm. Sci. 81:1-9.
Oliveira CA, Peres DD, Rugno CM, Kojima M, Pinto CASO, Consiglieri
VO, Kaneko TM, Rosado C, Mota J, Velasco MVR, Baby AR (2015).
Functional photostability and cutaneous compatibility of bioactive
UVA sun care products. J. Photochem. Photobiol. B. 148:154-159.
Oliveira-Junior RG, Souza GR, Guimarães AL, Oliveira AP, Araújo CS,
Silva JC, Pacheco AGM, Lima-Saraiva SRG, Rolim LA, Neto PJR,
Castro RN, Almeida JRGS (2015). Photoprotective, antibacterial
activity and determination of phenolic compounds of Neoglaziovia
variegata (Bromeliaceae) by high performance liquid
chromatography-diode array detector (HPLC-DAD) analysis. Afr. J.
Pharm. Pharmacol. 9(22):576-584.
Papucci L, Schiavone N, Witort E, Donnini M, Lapucci A, Tempestini A,
Formigli L, Zecchi-Orlandini S, Orlandini G, Carella G, Brancato R,
Capaccioli S (2003).
J. Biol. Chem. 278:2822028228.
Peres DA, Oliveira CA, Costa MS, Tokunaga VK, Mota JP, Rosado C,
Consiglieri VO, Kaneko TM, Velasco MVR, Baby AR (2015). Rutin
increases critical wavelength of systems containing a single UV filter
and with good skin compatibility. Skin Res. Technol. 1:1-9.
Ramos MFS, Santos EP, Bizarri CHB, Mattos HA, Padilha MRS, Duarte
HM (1996). Preliminary studies towards utilization of various plant
extracts as antisolar agents. Int. J. Cosmet. Sci. 18:87-101.
Regev-Shoshani G, Shoseyov O, Bilkis I, Kerem Z (2003).
Glycosylation of resveratrol protects it from enzymatic oxidation.
Biochem. J. 374:157-163.
Roberts MR, Paul ND (2006). Seduced by the dark side: integrating
molecular and ecological perspectives on the influence of light on
plant defence against pests and pathogen. New Phytol. 170:677-699.
Rozema J, van de Staaij J, Björn LO, Caldwell MM (1997). UV-B as an
environmental factor in plant life: stress and regulation. Trends Ecol.
Evol. 12:22-28.
Scalia S, Marchetti N, Bianchi A (2013). Comparative evaluation of
different co-antioxidants on the photochemical- and functional-
stability of epigallocatechin-3-gallate in topical creams exposed to
simulated sunlight. Molecules 18:574-587.
Sciavolino PJ, Vilcek J (1995). Regulation of metallothionein gene
expression by TNF- - s. Cytokine
7:242-50.
Seité S, Moyal D, Verdier M-P, Hourseau C, Fourtanier A (2000).
Accumulated p53 protein and UVA protection level of sunscreens.
Photodermatol. Photoimmunol. Photomed. 16:3-9.
Shyong EQ, Lu Y, Lazinsky A, Saladi RN, Phelps RG, Austin LM,
-
trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A
radiation (PUVA)-induced photodamage. Carcinogenesis 23:317-321.
Silva EES, Alencar-Filho JMT, Oliveira AP, Guimarães AL, Siqueira-
Filho JA, Almeida JRGS, Araújo ECC (2014). Identification of glycosil
flavones and determination in vitro of antioxidant and photoprotective
activities of Alternanthera brasiliana L. Kuntze. Res. J. Phytoch.
8(4):148-154
864 J. Med. Plants Res.
Stevanato R, Bertelle M, Fabris S (2014). Photoprotective
characteristics of natural antioxidant polyphenols. Regul. Toxicol.
Pharm. 69:71-77.
Thiele JJ, Schroeter C, Hsieh SN, Podda M, Packer L (2001). The
antioxidant network of the stratum corneum. Curr. Probl. Dermatol.
29:26-42.
Verschooten L, Declercq L, Garmyn M (2006). Adaptive response of the
skin to UVB damage: role of the p53 protein. Int. J. Cosmet. Sci.
28:1-7.
Vicentini FTMC, He T, Shao Y, Fonseca MJV, Verri Jr WA, Fisher GJ,
Xu Y (2011). Quercetin inhibits UV irradiation-induced inflammatory
cytokine production in primary human keratinocytes by suppressing
NF--168.
Vielhaber G, Grether-Beck S, Koch O, Johncock W, Krutmann J (2006).
-
---
Photochem. Photobiol. Sci. 5:275-282.
Wang Z, Agarwal R, Bickers D, Mukhtar H (1991). Protection against
ultraviolet B radiation-induced photocarcinogenesis in hairless mice
by green tea polyphenols. Carcinogenesis 12:1527-1530.
Wei H, Zhang X, Wang Y, Lebwohl M (2002). Inhibition of ultraviolet
light-induced oxidative events in the skin and internal organs of
hairless mice by isoflavone genistein. Cancer Lett. 185:21-29.
Widyarini S, Allanson M, Gallagher NL, Pedley J, Boyle GM, Parsons
PG, Whiteman DC, Walker C, Reeve VE (2006). Isoflavonoid
photoprotection in mouse and human skin is dependent on
metallothionein. J. Invest. Dermatol. 126:198-204.
Widyarini S, Husband AJ, Reeve VE (2005). Protective effect of the
isoflavonoid equol against hairless mouse skin carcinogenesis
induced by UV radiation alone or with a chemical cocarcinogen.
Photochem. Photobiol. 81:32-37.
Williams S, Tamburic S, Lally C (2009). Eating chocolate can
significantly protect the skin from UV light. J. Cosmet. Dermatol.
8:169-173.
Winkel-Shirley B (2002). Biosynthesis of flavonoids and effect of stress.
Curr. Opin. Plant Biol. 5:218-223.
Wölfle U, Esser PR, Simon-Haarhaus B, Martin SF, Lademann J,
Schempp CM (2011). UVB-induced DNA damage, generation of
reactive oxygen species, and inflammation are effectively attenuated
by the flavonoid luteolin in Free Radic. Biol. Med.
50:1081-1093.
Wölfle U, Haarhaus B, Schempp CM (2013). The photoprotective and
antioxidative properties of luteolin are synergistically augmented by
tocopherol and ubiquinone. Planta Med. 79:963-965.
Wu NL, Fang J-Y, Chen M, Wu C-J, Huang C-C, Hung C-F (2011).
Chrysin Protects Epidermal Keratinocytes from UVA- and UVB-
Induced Damage. J. Agric. Food Chem. 59:8391-8400.
Yang C, Wang Z (1993). Tea and cancer. J. Natl. Cancer Inst. 85:1038-
1049.
Yusuf N, Irby C, Katiyar SK, Elmets CA (2007). Photoprotective effects
of green tea polyphenols. Photodermatol. Photoimmunol. Photomed.
23:48-56
