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Review Article

Journal of Cosmetic Dermatology, 0, 1--17

Natural products as photoprotection


Nisakorn Saewan, PhD & Ampa Jimtaisong, PhD
School of Cosmetic Science, Mae Fah Luang University, Muang, Chiangrai, Thailand

Summary The rise in solar ultraviolet radiation on the earth’s surface has led to a depletion of
stratospheric ozone over recent decades, thus accelerating the need to protect human
skin against the harmful effects of UV radiation such as erythema, edema,
hyperpigmentation, photoaging, and skin cancer. There are many different ways to
protect skin against UV radiation’s harmful effects. The most popular way to reduce
the amount of UV radiation penetrating the skin is topical application of sunscreen
products that contain UV absorbing or reflecting active molecules. Based on their
protection mechanism, the active molecules in sunscreens are broadly divided into
inorganic and organic agents. Inorganic sunscreens reflect and scatter UV and visible
radiation, while organic sunscreens absorb UV radiation and then re-emit energy as
heat or light. These synthetic molecules have limited concentration according to
regulation concern. Several natural compounds with UV absorption property have
been used to substitute for or to reduce the quantity of synthetic sunscreen agents. In
addition to UV absorption property, most natural compounds were found to act as
antioxidants, anti-inflammatory, and immunomodulatory agents, which provide
further protection against the damaging effects of UV radiation exposure. Compounds
derived from natural sources have gained considerable attention for use in sunscreen
products and have bolstered the market trend toward natural cosmetics. This adds to
the importance of there being a wide selection of active molecules in sunscreen
formulations. This paper summarizes a number of natural products derived from
propolis, plants, algae, and lichens that have shown potential photoprotection
properties against UV radiation exposure-induced skin damage.
Keywords: natural product, photoprotection, sunscreens, UV radiation

into the following three categories: short wavelengths


Introduction
UVC (200–280 nm), medium wavelengths UVB (280–
The level of ultraviolet (UV) radiation reaching the 320 nm), and long wavelengths UVA (320–
earth’s surface has increased dramatically in recent 400 nm).3,4 UVC radiation is completely absorbed by
years.1 This phenomenon, in addition to the skin’s the oxygen and ozone molecules in the earth’s atmo-
overexposure to UV radiation, has contributed to a sphere.3 Although UVB radiation constitutes only 4–5%
steady increase in skin-related disorders in humans.2 of the total UV radiation,3 it is considered to be the
UV radiation, depending on its wavelength, is divided most active solar light component with skin sunburn
potency a thousand times greater than UVA radiation.
Thus, it is known as the “burning rays”. It penetrates
Correspondence: Nisakorn Saewan, School of Cosmetic Science, Mae Fah
Luang University, 333 Thasud, Muang, Chiangrai 57100, Thailand. E-mails: into skin’s epidermis layer and induces direct and indi-
nisakorn@mfu.ac.th; saewan.n@gmail.com rect adverse biological effects.5–8 UVA radiation typi-
Accepted for publication August 15, 2014
cally represents >90% of the total UV radiation

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Natural products as photoprotection . N Saewan & A Jimtaisong

reaching the earth’s surface.2 It is known to penetrate and urocanic acid (UCA), while UCA alone absorbs
deeper into the epidermis and dermis and advance the UVA radiation.12 The main lesions induced by UVB
generation of reactive oxygen species (ROS).9 Chronic radiation are cyclobutane pyrimidine dimers (CPDs)
exposure to UVA can damage underlying structures in and 6-4 pyrimidine pyrimidone (6-4PP). These photo-
the dermis and cause premature photoaging of the products block RNA transcription leading to activation
skin, such as skin sagging and wrinkles.10,11 Hence, it of p53 gene that induces apoptosis of irradiated kerati-
is known as the “aging rays”. nocytes.13 Photosensitization mechanism, on the other
The first defense against the sun is production of hand, endogenous and/or exogenous sensitizers absorb
melanin.2 This pigment absorbs dangerous UV rays UV light and then change from a ground state to an
and thus protects skin cells from the detrimental effects excited state, resulting in further reactions leading to
of UV exposure. In certain circumstances, the amount formation of ROS and reactive nitrogen species (RNS).
of melanin produced is not sufficient to protect the The predominant ROS produced upon UV radiation are
skin, resulting in development of sunburn.2 Therefore, hydroxyl radical, superoxide anion, and peroxyl radical
the protection of skin from UV radiation by some other and their active precursors, namely singlet oxygen,
method is an urgent concern. Multiple photoprotective hydrogen peroxide, and ozone. The major RNS
methods can be utilized to provide protection against produced by UV radiation are nitric oxide and nitric
harmful effects of UV exposure. Physical barriers such dioxide.14,15 ROS is constantly generated in keratino-
as clothing and sunglasses can serve as an effective cytes and fibroblasts, and it is rapidly removed by non-
way to shield UV rays from the skin and eyes, respec- enzymatic (ascorbic acid, tocopherol, ubiquinol, and
tively. Topical application with sunscreen products is a glutathione [GSH]) and enzymatic antioxidants (cata-
strategy for protecting the skin from UV radiation by lase [CAT], superoxide dismutase [SOD], thioredoxin
blocking the UV radiation exposed on the epidermis.2,3 reductase, glutathione peroxidase [GPx], and glutathi-
Nowadays, there is a worldwide trend to develop high one reductase) to maintain a balance between prooxi-
UV protection sunscreens using low concentrations of dant and antioxidant, resulting in cell structure
chemical sunscreens. Naturally occurring compounds stabilization. However, the presence of excess free radi-
have gained considerable attention as protective agents cals leads to loss of cellular integrity, due to modifica-
because of their broad biological activities such as UV tion of DNA and abnormal expression of cellular genes.
absorption, antioxidant, and anti-inflammatory.2,3,5 UV-generated ROS affect mitogen-activated protein
Several studies demonstrated that phenolic acids and kinase (MAPK) pathway, followed by nuclear factor
flavonoids derived from propolis, tea, grape, fern, and kappa B (NF-jB) and activator protein 1 (AP-1) fami-
milk thistle provide photoprotection through reduction lies of transcription factor,16 which may both contrib-
oxidative stress, inflammation, and immunosuppres- ute to induction of heme oxygenase-1 (HO-1) and
sion. Topical application of flavonoids from caper matrix metalloproteinases (MMPs) in the skin. HO-1
shows effective inhibition of erythema on the healthy induction may elevate cellular iron levels that may
human. The protection efficacy of mycrosporine-like promote further ROS generation. An increase in MMPs
amino acids (MAAs) from marine red alga and liche- results in the extracellular matrix protein degradation,
nized ascomycete against UV radiation damage is well causing wrinkle formation and metastases.16 Further-
established. The following section deals with the more, ROS damages cell membranes by peroxidation of
adverse effects of UV radiation on skin and its protec- fatty acids within the phospholipid structure of the
tion by natural compounds. membrane.15
Extensive and chronic exposure to UV radiation asso-
ciated with abundant ROS/RNS generation lead to oxi-
Mechanism of UV-induced biological damage
dative damage that may result in inflammation as well
UV photons are known to mediate skin damage via as local and systemic immunosuppression.17,18 Altera-
two different mechanisms: direct absorption and photo- tions in the morphology and function of antigen-pre-
sensitization. In the direct absorption mechanism, the senting Langerhans cells, release of immunosuppressive
cellular chromophores absorb UV radiation and trans- cytokines, and enhanced prostaglandin synthesis have
form the absorbed energy into a biochemical signal,12 all been reported in the existing literature.19–21 After
triggering the subsequent biological responses. The cel- exposure to UV radiation, it may trigger the upregula-
lular chromophores absorbing UVB radiation are tion of the tumor necrosis factor-alpha (TNF-a), which
known to be the nucleic acids, amino acids (such as represents an important skin inflammatory cascade22
tryptophan and tyrosine), quinines, flavins, porphyrins, and release of pro-inflammatory cytokines, interleukin

2 © 2015 Wiley Periodicals, Inc.


Natural products as photoprotection . N Saewan & A Jimtaisong

(IL-1).23–25 This may subsequently trigger the synthe-


Natural products as photoprotection
sis of other proinflammatory cytokines, IL-6 and IL-
8.23,26–28 This release of proinflammatory cytokines is Natural products are secondary metabolites produced
believed to be due to DNA lesions characteristic to UV by living organisms found in nature. The production
radiation exposure, CPDs, and 6-4 PP.29–31 UVB radia- of these metabolites is often a specific response of pro-
tion, in addition, induces the cytokine IL-10 and IL-12. ducing organisms to their environment, which has
However, UVA radiation induces only the IL-10, a key contributed to their success in growth and continuity
mediator of UV radiation-induced immunosuppres- of their species.40 Several natural organisms, especially
sion.10,32 On the contrary, IL-12 has been shown to those exposed to intense radiation, have evolved a
repair UV-induced DNA damage in the skin.33 Depend- variety of photoadaptive mechanisms including pro-
ing on the severity of the skin’s DNA damage following duction of antioxidant and UV-absorbing secondary
UV exposure, the keratinocytes in the skin can pro- metabolites.40 The common feature of UV screening
gress to either apoptosis or DNA repair pathways.34,35 molecule is its p-electron system, which is primarily
If DNA damage is irreparable, then the cell cycle is found in conjugated bond structures that may be rep-
arrested and keratinocyte is transformed into a sun- resented both in linear chained molecules with alter-
burn cell, which is an early morphologic indicator of nating single and double bonds and in many aromatic
epidermal cell apoptosis.33–35 and cyclic compounds containing electron reso-
nance.40 The important secondary metabolites act as
UV blockers including phenolic acids, nonflavonoids,
Sunscreens for photoprotection flavonoids, lichen polyphenols, terpenoids, and my-
Topical application of sunscreen products can protect cosporine-like amino acids. The structures of these
the skin from the harmful effects of solar UV radia- compounds are shown in Figures 1–4. These com-
tion by absorbing or reflecting UV radiation at the pounds can prevent penetration of radiation into the
skin’s surface. Based on their protective mechanism, skin, resulting in the reduction of inflammation, oxida-
sunscreen agents can be classified into two broad cat- tive stress, and DNA damaging effects.41 In addition to
egories: inorganic and organic.36 Inorganic com- UV radiation absorption ability, some natural com-
pounds are inert particles reflecting the photons of pounds were also found to reduce inflammation, oxi-
both UVA and UVB radiations away from the skin.36 dative stress and affect multiple signaling pathways to
These inert particles are often visible on the skin’s protect the skin against UV radiation inflicted dam-
surface and were found to have a cosmetically unde- age.41 Hence, the naturally occurring substances have
sirable visual effect. A typical inorganic sunscreen gained considerable attention for their use as effective
includes zinc oxide and titanium dioxide. The chemi- photodamage reductants in humans via various mech-
cally inert property of these agents does not cause anisms due to their involvement in multiple phototox-
allergic sensitization.37 Organic sunscreens are gener- icity pathways. Subsections below present a review of
ally aromatic compounds conjugated with carbonyl the protection properties of various natural com-
group that allows the molecule to absorb UV rays pounds, derived from the propolis, plants, alga, and
and release lower energy rays, thereby preventing the lichen, to UV radiation.
skin from damaging effects of UV radiation.38 Organic
sunscreens, being invisible on the skin’s surface, have
Propolis
more cosmetic appeal.38 Examples of commercial
absorbing ingredients are oxybenzone, sulisobenzone, Propolis is a natural product derived from plant resins
and octylmethoxycinnamate. However, these mole- and collected by honeybees, which is typically used as
cules have limited use because they may be activated a glue and draught extruder for beehives.42 Its chemi-
by UV radiation and produce photosensitizer mole- cal composition, color, aroma, and biological activities
cules which may consequently interact with cutane- are complex, which depend on plant resin collection
ous molecules, causing adverse skin reactions.39 location, time, and plant source.43 It has been used in
Therefore, these compounds have limited concentra- traditional medicine as an antioxidant, immune-stimu-
tion in sunscreen formula. It is difficult to achieve lating, anti-inflammatory, antiseptic, antimycotic, bac-
high sun protection using only synthetic UV filters teriostatic, astringent, spasmolytic, anesthetic, and
from a regulatory list. Naturally occurring substances anticancer agent.44–46
become increasingly important to incorporate in sun- Due to its UV-absorbing property, the photoprotec-
screen formulation. tion of the propolis has been studied by many

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Natural products as photoprotection . N Saewan & A Jimtaisong

O O O

OH OH O

HO HO HO
1,1-dimethylallylcaff eate
OCH3 R R = H; p-Coumaric acid OH
Vanillic acid R = OH; Caff eic acid
R = OCH3; Ferulic acid

O O
OH
O OH

HO HO
OH OH HO C OH
Caf f eic acid phenethyl ester Chlorogenic acid O

OH HO OH

R1 R2
OH O OH

HO Bisdesmethoxycurcumin; R1 = H: R2 = H
Desmethoxycurcumin; R1 = H: R2 = OCH3
Resveratrol Curcumin; R1 = OCH3: R2 = OCH3

Figure 1 Nonflavonoid polyphenols as photoprotection compounds.

researchers. Soares dos Reis et al.47 have demonstrated known to be effective antioxidants and have a high
photoprotective effect of the green propolis from Vale rate of UV absorption. Moreover, the Italian propolis
do Acßo, Brazil, by in vitro measurement of the sun pro- extract inhibited lipid peroxidation of linoleic acid (LA)
tection factor (SPF) of topical formulations, gels, and in sodium dodecyl sulfate (SDS) micelles. The photopro-
oil-in-water emulsion. The formulations containing tection, including SPF, UVA/UVB ratio and critical
40% of the hydroalcoholic propolis extract possessed wavelength values of the Italian propolis extract, and
SPF value of 10.47 Later, Fonseca et al.48 have investi- isolated compounds were evaluated compared to the
gated the chemical constituents and potential use of commercial UV filters, tinosorb S, oxybenzone, octinox-
green and brown Brazilian propolis extracts for pre- ate, and padimate O. The results revealed that the Ital-
venting UV irradiation-induced oxidative stress in the ian propolis extract and its components protected
skin. The results illustrated that the green propolis against UV radiation, better than those of commercial
extract contained greater amounts of active com- UV filters.50 Recently, Bolfa et al.51 have investigated
pounds, such as coumaric acid, drupanin, baccharin, the antioxidant, anti-inflammatory, antiapoptotic, and
and artepillin C, resulting in higher antioxidant activ- antigenotoxic effects of Romanian propolis extract. The
ity. Also, topical pretreatment on the animals with major compounds isolated from Romanian propolis
both Brazilian propolis extracts has shown 14% GSH were coumaric acid, ferulic acid, and quercetin. Topi-
depletion recovery and promising antioxidant activity cally administered, the Romanian propolis extract in a
against the oxidative stress in the skin.48 The protec- Swiss mouse model significantly attenuated the mal-
tive effects of Sydney propolis against photodamage ondialdehyde (MDA) formation, restored GPx activity,
were tested on hairless mice.49 Topical application of a decreased IL-6 levels, reduced the epidermal hyperpla-
crude ethanolic extract of Sydney propolis was found sia and dermal inflammation, and reduced sunburn
to effectively reduce cutaneous inflammation, immuno- cell formation along with the inhibition of CPDs forma-
suppression, and lipid peroxidation induced by UV tion.51
exposure.49 In other work, reported by Gregoris and
coworker,50 the chemical constituents of the ethanolic
Red clover
extract from Italian propolis were found to be three
caffeic acids (caffeic acid, caffeic acid phenethyl ester, Red clover (Trifolium pratense L.) is an important peren-
and 1,1-dimethylallyl-caffeate) and three flavonoids nial forage legume that is commonly grown through-
(kaempferol, quercetin, and galangin), which are out the world.52 It is one of the botanical dietary

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Natural products as photoprotection . N Saewan & A Jimtaisong

OH OH
B OH
HO O HO O
A C HO O
OH

OH O O EGCG
OH O
OH OH
Crysin Apigenin O

OH OH
OH
OH OH
OH
HO O
HO O
HO O HO OH
O
O OH
OH OH O
OH O
O
OH O Rutin HO O
OH HO
Quercetin Genistein HO
OH

HO O
HO O HO O

HO
O
OCH3 O O
OH OCH3
Formononetin Daidzein Biochanin A

b CH OH CH2OH
2
H B D H
HO O OCH3 HO O OCH3
a
A C E
OH OH OH OH
H Silibin A H Silibin B
OH O OH O

OH OCH3

OH OH

HO +
HO O+ O
OCH3

O HO
O HO
OH
OH O OH
O OH
Malvidin 3-glucoside
OH
OH
OH
Cyanidin 3-glucoside OH

Figure 2 Flavonoids as photoprotection compounds.

supplements used by women for menopausal hot UV radiation.54,55 Moreover, equol protected immuno-
flashes.53 Red clover contains high amounts of estro- suppression by inactivation of the downstream action
genic isoflavones, daidzein, genistein, formononetin, of cis-UCA, a major UV-induced immunesuppressive
and biochanin A.53 After UV exposure, topically photoproduct produced in the skin.54
applied isoflavonoids derived from red clover and some
metabolically related compounds in hairless mice
Soybean
resulted in the primary isoflavones, daidzein, biochanin
A, and formononetin were inactive, whereas lotions of Soybean (Glycine max L.), due to its high nutritional
genistein and its metabolites, equol, isoequol, and de- value from such vitamins as A, B, C and minerals, is
hydroequol were found to have increased potential in an important crop for human and animal consump-
reducing the inflammatory edema reaction and the tion.56 It consists of more than 36% protein, 30%
photoimmune suppression of contact hypersensitivity carbohydrates, and is an excellent source of dietary
(CHS) induced by moderate doses of solar-simulated fiber. It also consists of 20% oil, which makes it an

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Natural products as photoprotection . N Saewan & A Jimtaisong

O O
O

Sargaquinoic acid
Plastoquinones
O O

O
O

Sargachromenol HO
O O

O
C

O
O
HO OH
Fucoxanthin
O
OH

HO Astaxanthin
O
HO
HO
CO2H
CO2H
N
N
MeO OH
MeO
OH
OH
HN
HN
OH OH
HO2C OH OH O
Shinorine HO2C
Porphyra O OH
HO OH
OH
O O
OH HO OH OH
HO OH HO OH
HO OH
OH O
O O

OH
HO OH HO OH
Phlorotannins Dieckol

Figure 3 Polyphenols, mycrosporine-like amino acids, and terpenes as photoprotection compounds from algae.

important crop for producing edible oil. Soybean cake, liferating cell nuclear antigen (PCNA) expression in
a by-product of soybean oil processing, contains a high response to UVB exposure.60
amount of isoflavones.57,58 The photoprotection of soy-
bean cake which contains 12 soy isoflavones has been
Caper
demonstrated by Chiang et al.59 The extract inhibited
UVB radiation-induced keratinocyte death, release of The use of caper (Capparis spinosa) dates to the Greek
hydrogen peroxide (H2O2), and MAPK phosphoryla- and the Roman times. It was used for medicinal pur-
tion.59 Later, the soybean cake extract was further poses.61 The whole extracts of the floral buttons of this
purified into subfraction by chromatography technique. plant is reported to possess hydrating properties on the
A fraction, which contains the aglycone group (daidz- dry, aged, and undernourished skin.62 The major con-
ein, genistein, and glycitein) and acetylglucoside group stituents of lyophilized extract of caper were identified
(acetyldaidzin, acetylgenistin, and acetylglycitin), pre- as kaempferol, caffeic, ferulic, coumaric, and cinnamic
vented human keratinocyte apoptosis, attenuated the acids.63 Topical application of sunscreen product con-
level of erythema and transepidermal water loss taining caper extract on the healthy human showed a
(TEWL), reduced epidermal thickness, increased CAT 59.6% inhibition of erythema, which is more effective
activity, inhibited cyclooxygenase 2 (COX-2), and pro- than tocopherol acetate (22%).63

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Figure 4 Polyphenols as photoprotection compounds from lichen.

Almond Milk thistle

Almonds (Prunus amygdalus Batsch) are one of the Milk thistle (Silybum marianum L.) is an important
most popular tree nuts and rank high in tree nut pro- medicinal plant that has volatile oils and other second-
duction.64 They are typically used as snacks and as ary metabolites, known as silymarin.70 The principal
ingredients in a variety of processed foods, especially components of silymarin include the diastereoisomers
in bake goods.64 The seeds are rich in polyphenolic silibinin A and silibinin B in a roughly 1:1 ratio, the
compounds, especially flavonoids and phenolic diastereoisomers isosilibinin A and isosilibinin B, silicri-
acids.65,66 The UV protection property of almond stin, and silidianin.71 The main chemical constituents
extract was estimated in mice skin.67 Topical treat- of silymarin are silibinin A and silibinin B, and repre-
ment of extract prior to UV radiation exposures sent 50–60% of the components of silymarin, which
showed a strong antioxidant activity via significantly are the most active components.72,73 Silymarin exhib-
decreased levels of lipid peroxidation and increased its a high antioxidant capability owing to the polyphe-
levels of GSH.67 nol hydroxyls and the ability to form complexes with
transition and other metal ions in 3,4- or 4,5-posi-
tions.74 Topical application of silymarin protected
Flame of the forest
mouse skin against UVB-induced suppression of CHS
Flame of the forest (Spathodea campanulata), also known response to contact sensitizer dinitrofluorobenzene and
as the Fountain Tree, African Tulip Tree, or Nandi infiltration of inflammatory leukocytes, which are
Flame, is an ornamental plant that grows along the responsible for the generation of oxidative stress.75,76
roadsides.68 The flowers of this plant consist of flavo- The treatment also resulted in significant reduction of
noids that absorb UV radiation with maximum absor- UVB-induced immunosuppressive cytokine IL-10 pro-
bance at 200–240 nm, while good absorbance at ducing cells and their production.75,76 Moreover,
240–325 nm. The author suggested that the strong to silymarin was found to decrease UV radiation-induced
moderate absorption of this plant makes it a better and apoptotic cell death of epidermal cells through repair of
safer alternative to classical organic sunscreens.69 damaged DNA.77 Therefore, silymarin inhibited photo-

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Natural products as photoprotection . N Saewan & A Jimtaisong

carcinogenesis via inhibition of UVB-induced oxidative Pomegranate


stress, inflammation, and suppression of immune sys-
Pomegranate (Punica granatum) is a tropical fruit
tem.5,78,79
lauded in ancient times (as part of the Old
Testament of the Bible, Jewish Torah, and Babylo-
Tea nian Talmud) as a sacred fruit conferring powers of
fertility, abundance, and good luck.97 Pomegranate
Tea is among the most consumed beverages around
extract is a source of anthocyanins and hydrolyzable
the world, and it is currently cultivated in at least 30
tannins with potent antioxidant and anti-inflamma-
countries. Freshly harvested tea leaves are processed
tory properties. The protection of skin against the
differently to produce oolong tea (2%), green tea
adverse effects of UVA and UVB radiation of the
(20%), and black tea (78%).80 Green tea is prepared
pomegranate extract has been established.98,99 Treat-
from fresh tea leaves, and is widely consumed in Japan
ment of reconstituted human skin (EpiDerm) with
and China. Western cultures favor black tea, which is
pomegranate extract before UVB irradiation inhibited
prepared through oxidation curing process of macera-
the induction of CPD, 8-dihydro-2-deoxyguanosine
tion and exposure to atmospheric oxygen.81,82 Tea is
(8-OHdG), protein oxidation, cell proliferation, and
popular, not only for its taste, but also for its high lev-
synthesis of MMPs (MMP-1, MMP-2, MMP-3, MMP-
els of antioxidants, specifically, catechins. () Epigallo-
7, MMP-9, and MMP-12).98 In normal human epi-
catechin-3-gallate (EGCG), the most abundant catechin
dermal keratinocytes, the treatment with pomegran-
in green tea, accounts for approximately 65% of total
ate extract reduced UVA radiation-induced cell
catechin content. These polyphenolic compounds are
damage by inhibition of keratinocyte proliferation
capable of scavenging free radicals such as lipid free
and apoptosis.99
radicals,83,84 superoxide radicals,85 hydroxyl radi-
cals,86 hydrogen peroxide,87,88 and singlet oxygen.89,90
The photoprotection property of green tea polyphenols Red orange
was demonstrated in several studies.91–94 In the ani-
Red oranges (Citrus sinensis varieties: Moro, Tarocco
mal model, topical pretreatment of green tea polyphe-
and Sanguinello), also known as blood oranges typi-
nolic on the skin prior to UV irradiation was found to
cally grown in Italy, are an important dietary source
increase the protection against UVB-induced immune
of anthocyanins, such as cyanidin-3-glucoside and
suppression and photocarcinogenesis.91,92 In the
cyanidin-3-(6-malonyl)-glucoside, which are responsi-
human model, topical pretreatment with green tea
ble for their brilliant red color.100–102 Topical appli-
extract before UV exposure resulted in reduced DNA
cation of the extract immediately after skin exposure
damage and erythema formation. This is due to the
to UV radiation was found to provide an efficient
protection of DNA repair enzymes via the inactivation
protection against photooxidative skin damage,
of ROS and UVB radiation absorption ability of the
including protective effect on the DNA cleavage, free
green tea polyphenolic.93,94
radical scavenging capacity, inhibition of xanthine
oxidase activity, and antilipoperoxidative capacity.103
Grape

Grapes (Vitis vinifera) are among the most commonly Bilberry


consumed fruits around the world. Grape seeds are a
Bilberry (Vaccinium myrtillus L.), commonly known as
rich source of polyphenols (60–70%), that is, cate-
blueberry, is a rich source of anthocyanins. It is widely
chin, epicatechin and oligomeric proanthocyanidins.95
reported for their antioxidant activities such scaveng-
The excellent antioxidant, strong anti-inflammatory,
ing superoxide, reducing hydrogen peroxide radicals,
and antiproliferative activity of the grape seeds come
and inhibiting of lipid peroxidation.104,105 Photoprotec-
from the polyphenolic phytoalexin namely resveratrol.
tion of bilberry fruit extract was investigated in HaCaT
Topical application of resveratrol to SKH-1 hairless
keratinocytes. Pre- (1 h) or post-treatment (4 h) of the
mice before exposure to UVB radiation resulted in sig-
extract containing 25% anthocyanins in the cells
nificant inhibitions of UVB-mediated skin edema,
resulted in the reduction of UVA radiation-stimulated
inflammation, cyclooxygenase (COX) and ornithine
ROS formation, attenuation of UVA radiation-caused
decarboxylase (ODC) induction, and generation of
peroxidation of membrane lipids, and depletion of
hydrogen peroxide (H2O2) and lipid peroxidation in
intracellular GSH.106
the skin.96

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Natural products as photoprotection . N Saewan & A Jimtaisong

Bog blueberry
disorders, although with variable success.119 The
hydrophilic extract of the leaves of P. leucotomos con-
Bog blueberry (Vaccinium uliginosum L.) is rich in an- sists of coumaric acid, ferulic acid, caffeic acid, vanillic
thocyanins, that is, cyanidin-3-glucoside, petunidin-3- acid, 3-caffeoylquinic acid, and chlorogenic acid.120
glucoside, malvidin-3-glucoside, and delphinidin-3-glu- This extract provided antioxidant activities, inhibiting
coside. Bog blueberry anthocyanins have been effective of ROS generation, scavenging the superoxide anion,
against UVB radiation-induced toxicity accompanying and SOD.121–123 At a cellular level, the extract showed
the production of ROS. The extract effectively protected a significant reduction in UV radiation-mediated cellu-
the skin and reduced the photoaging process by block- lar apoptosis and necrosis and a profound inhibition of
ing collagen destruction through modulation of the extracellular matrix remodeling.119 The important role
NF-jB responsive and MAPK-dependent pathways.107 in photoprotection of fernblock is inhibiting skin ery-
thema, preventing damage to DNA, inhibiting UV-
Strawberry
induced AP-1 and NF-jB, and protecting endogenous
skin natural antioxidant systems.119
Strawberry (Fragaria 9 ananassa) is an important die-
tary source of natural antioxidants. Anthocyanin
Turmeric
extract of strawberry shows strong anti-inflamma-
tory,108 antioxidant,109 antimutagenic,110 and anticar- Turmeric (Curcuma longa L.) is a rhizomatous herba-
cinogenic111 properties. The photoprotective properties ceous perennial plant of the ginger family, Zingibera-
of strawberry have been demonstrated in human der- ceae. It is native to South Asia, but is now widely
mal fibroblasts.112 The extract exhibited ability to block cultivated in tropical and subtropical regions of the
the collagen destruction and inflammatory responses world. It is commonly used as a spice and as a medi-
via transcriptional mechanisms of the NF-jB and cine, particularly in Asia. It is primarily used for the
MAPK signals. Additionally, the extract increased cel- treatment of inflammatory-related conditions in ayurv-
lular viability and diminished DNA damage on UVA edic medicine and in addition also used as a stimulant,
radiation-induced skin damage.112 aspirant, carminative, cordeal, emmenagogue, astrin-
gent, detergent, diuretic, and martirnet in traditional
Foti
Chinese medicine.124–126 Three curcuminiods, bisde-
methoxycurcumin, demethoxycurcumin, and curcu-
The root of foti (Polygonum multiflorum Thunb) is used min, have been identified as the active principle of
in traditional medicine and is officially listed in the turmeric rhizomes. Turmeric has been reported to exert
Chinese Pharmacopoeia.113 It was found to have anti- pharmacological activities such as anticancer,127,128
bacterial, antifungal, and anti-aging properties, which antidiabetes,129 oxidation,130 and treatment of Alzhei-
are typically associated with cellular antioxidant activ- mer’s disease.131 Curcumins have an anti-inflamma-
ity.114 The main active constituents in the foti’s roots tory effect by inhibiting the NF-jB and MAPK
were characterized as polyphenolic compounds, includ- signaling pathways, reducing the expression of induc-
ing hydroxyl anthraquinones, stilbenoids, and proanth- ible nitric oxide synthase (iNOS) and COX-2.132,133
ocyanidins,115,116 which are responsible for radical Jang et al. have evaluated the antiwrinkle effects of the
scavenging activity.117 The antioxidant effects of foti three turmeric curcuminoids in keratinocytes and
extract against skin damage induced by UVB irradia- fibroblasts. All curcuminoids inhibited UVB radiation-
tion have been established by Hwang et al.118 in induced TNF-a mRNA expression. Specifically, the
female SKH-1 hairless mice models. Topical application demethoxycurcumin and bisdemethoxycurcunim inhib-
of the extract following UV irradiation showed strong ited UVB radiation-induced NF-jB activation in the
inhibition of oxidative stress, specifically, the destruc- HaCaT keratinocytes and reduced the expression of
tion of the SOD enzyme.118 MMP-1 in both keratinocytes and fibroblasts.134

Fernblock Ginseng
Fernblock (Polypodium leucotomos) is a tropical fern Ginseng (Panax ginseng), also known as Korean or
plant belonging to a Polypodiaceae family. It is com- Chinese ginseng, is a widely used traditional herbal
monly used as a traditional medicine in South America medicine having multifunctional activities, anti-
to make poultices and treat psoriasis and other skin inflammatory, antioxidant,135 antitumor promoting,136

© 2015 Wiley Periodicals, Inc. 9


Natural products as photoprotection . N Saewan & A Jimtaisong

and anti-aging137 activities. Commercially available Coffee


ginseng is classified into white, red, and sun ginseng.
Coffee is one of the most popular beverages consumed
White ginseng is made by peeling the fresh ginseng
in the world. Two species of coffee have been commer-
roots and drying them without the following steaming
cial importance: Arabica coffee (Coffea arabica) and
process. Red and sun ginsengs are made by steaming
Robusta coffee (Coffea canephora).145 Coffee stands out
and drying the fresh ginseng to preserve them for an
as a dietary source of potential antioxidants, such as
extended period of time.138,139 Sun ginseng is steamed
caffeine, chlorogenic acid, and hydroxycinnamic acids.
at a higher temperature compared to red ginseng.139
In 1988, L’oreal researcher discovered sun filter com-
Photoprotection of red and sun ginseng has been dem-
pound in coffee bean oils that was obtained as a resi-
onstrated by Lee and coworker on mice model.139,140
due from aqueous extraction of the roasted coffees.
The red ginseng-treated mice showed a significant
This oil promoted natural browning of skin, while at
decreased wrinkling score, minimal epidermal hyper-
the same time also protected skin against solar radia-
plasia, slightly increased dermal cellularity, and lack of
tion and development of skin burns.146 In other work,
proliferation of cysts.140 Sun ginseng exerted an
the SPF of lipid fraction of green coffee beans from 10
anti-inflammatory activity by reducing the nitric oxide
species was investigated.147 The results showed signifi-
production and iNOS mRNA synthesis in HaCaT kerati-
cant variability for SPF ranges from 0.0 to 4.1 and
nocytes and human dermal fibroblasts. Sun ginseng
C. arabica species showed high SPF (1.50), which made
inhibited UVB-induced COX-2 expression and TNF-a
it a choice for applications in cosmetics. Caffeine is a
transcription in HaCaT cells.139
natural compound in coffee with UV absorption prop-
erty, and it has been reported to inhibit ROS-mediated
English ivy lipid peroxidation.148 The radiation protection ability of
caffeine in an animal model has also been reported by
English ivy (Hedera helix) is well known for its ability
George et al.149 Only a low concentration of caffeine
to climb onto and strongly adhere to a variety of solid
was required to suppress DNA cross-linking.149 Topical
substrates by secreting an adhesive composed of poly-
application of caffeine 0.5 h before a high dose of UVB
saccharide and spherical nanoparticles.141 Based on
radiation decreased UVB-induced thymine dimer for-
four criteria including the ability to absorb and scatter
mation and sunburn lesions.150
ultraviolet light, toxicity to mammalian cells, biode-
gradability, and potential for diffusion through the
skin, the potential use of ivy nanoparticles in sun- Basil
screen was evaluated comparison to TiO2 nanoparti-
cles. The results showed that the ivy nanoparticles Basil (Ocimum basilicum, Linn.) belongs to Lamiaceae
were more efficient in blocking UV light, less toxic to plant family and is native to the subtropics, especially,
HeLa cells, easily biodegradable through several diges- existing throughout the Mediterranean region and
tive techniques, and had a limited potential to pene- India. Basil is widely used as traditional medicine for
trate through human skin in a mathematical model the treatment of several ailments. The SPF value of
compared to TiO2 nanoparticles.141,142 sunscreen cream containing essential oil of basil as an
active ingredient was found to be 1.19, with ultra boot
star rating value of 1.151
Broccoli

Broccoli (Brassica oleracea var italica) is a cruciferous


Alga
vegetable, a member of the cabbage family (Crucife-
rae).143 This vegetable is a rich source of sulforaphane Algae is found wherever there is a light to carry out
and has anticarcinogenic, antidiabetic, and antimicro- photosynthesis in places such as in the sea, rivers,
bial properties.143 Topical application of sulforaphane- and lakes, on soil and walls, and in animals and
rich extracts of broccoli sprouts upregulated phase 2 plants (as symbiotic partners collaborating together).
enzymes in mice and human skin was found to protect Based on their pigmentation, Harvey was the first,
against UV radiation-induced inflammation and edema who divided the algae into four categories including
in the mice, and reduced susceptibility to erythema in red algae (Rhodophyta), brown algae (Hetero-
humans.144 This effect was attributed to the produc- kontophyta), green algae (Chlorophyta), and diatoma-
tion of protective intracellular enzymes that defended ceae.152 In recent years, a wide range of studies have
the cells against UV radiation-induced damage.144 demonstrated photoprotective effect of several groups

10 © 2015 Wiley Periodicals, Inc.


Natural products as photoprotection . N Saewan & A Jimtaisong

of multicellular algae. Methanol extract of a red alga intestinal Caco-2 cells.158 These algal extracts have
(Corallina pilulifera) showed a potent antioxidant acti- depicted a tremendous alteration in antioxidants, such
vity, protective effect on UVA radiation-induced oxi- as SOD and GSH, and also have shown a protective
dative stress, and prominent reduction of the effect against UVA radiation-induced DNA damage.158
expression of UV radiation-induced MMP-2 and MMP-
9 in a dose-dependent manner.153 Two MAAs, por-
Lichens
phyra-334 and shinorine, were isolated from the red
alga Porphyra rosengurttii, which was evaluated in the Lichens are symbiotic organisms of fungi and algae,
mice skin model.154 Topical application of the gel con- which are the earliest colonizers of terrestrial habitats
taining the combination of porphyra-334 and shino- on earth. They are widely distributed around the
rine demonstrated that it protected against UV world, from the Arctic to tropical regions, and from
radiation-induced sunburn cell formation, as well as the plains to the highest mountains. Over 800 second-
corneum stratum, malpighian, dermal and hypoder- ary metabolites, which are present in the lichens such
mal thickening and other structural and morpho- as aliphatic, cycloaliphatic, aromatic, and terpenic
logical alterations, contributing to maintain the compounds, were isolated and showed interesting bio-
antioxidant defense mechanism of the skin as well as logical and pharmacological activities.159,160 Usnic
Hsp70 expression, a potential biomarker for acute UV acid, depsides, and depsidones are prominent secondary
damage. Three marine algal polyphenol, phloroglucin- lichen metabolites. Usnic acid is used in pharmaceuti-
ol, eckol, and dieckol, were isolated from Ecklonia cava, cal preparations against infections, bacterial eczema,
an edible marine brown alga species. The photopro- mastitis, furunculosis, and polydermy.161,162 Depsides
tective effect of these isolated compounds against UVB and depsidones exhibit anti-inflammatory, analgesic,
radiation-induced photooxidative stress was examined antipyretic, antibacterial, antifungal, and anticancer
by 20 ,70 -dichlorodihydrofluorescein diacetate (DCFH- properties.159,163,164 According to the absorption in
DA), 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazoli- UV region and antioxidant power, lichen extracts were
um bromide (MTT), comet assay, and morphological considered as potential sunscreens.165 Rancan et al.
changes in fibroblast.155 The prominent inhibitory isolated five compounds, usnic acid, 1-chloropannar-
activity against melanogenesis and effectively reduced ine, epiphorelic acid I and II, and calicin, from chilean
UVB radiation-induced cellular damage were found in lichen extract. The photoprotection factors were ana-
phlorotannins and dieckol. Phlorotannins showed the lyzed against the references, Nivea sun Spray LSF 5,
highest reduced intracellular ROS due to UVB radia- octylmethoxycinnamate (OMC), and butyl meth-
tion and increased cell viability. Dieckol showed oxydibenzoylmethane (BM-DBM). Most of the single
strong protective properties against UVB radiation- compounds were found to provide UV protection fac-
induced DNA damage via damaged tail intensity and tors similar to that of the reference compounds, and
morphological changes in fibroblast.155 Plastoquinon- usnic acid was found to be the best UVB filter.166 Col-
es, sargaquinoic acid, and sargachromenol are the lemin A, a mycosporine isolated from the lichenized
major components of a brown alga (Sargassum sagami- ascomycete (Collema cristatum), prevented UVB-induced
anum). The therapeutic effect in the protection against cell destruction in a dose-dependent manner, partially
UVB of these compounds was investigated in the Ha- prevented CPDs formation in cultured human keratino-
CaT cells and hairless mice.156 These plastoquinones cytes, and completely prevented UVB-induced ery-
showed a reduction of UVB radiation-induced apopto- thema on human skin.167 Russo et al.165 isolated
sis due to the activation of caspases.156 The protective sphaerophorin from Sphaerophorus globosus and panna-
effect of fucoxanthin, a natural carotenoid isolated rin from different species of the genus Psoroma (Psoro-
from brown alga Sargassum siliquastrum, was investi- ma reticulatum, Psoroma pulchrum, Psoroma palladium)
gated in the human fibroblast via DCFH-DA, MTT, and evaluated for their protection of DNA damage and
and comet assays.157 The results suggested that fuco- inhibition the growth of melanoma. Both compounds
xanthin had the ability to protect against oxidative showed a protective effect on plasmid DNA damage,
stress induced due to UVB radiation and had exhibited a SOD-like effect, and inhibited the growth of
increased the cell survival rate.157 The ability of an melanoma cells, inducing an apoptotic cell death,
algal extract that contains a high level of astaxanthin demonstrated by the fragmentation of genomic DNA
to protect against UVA-induced DNA damage was and by a significant increase of caspase-3 activity.165
investigated using single cells, human skin fibroblasts Recently, Millot et al.168 have performed preliminary
(1BR-3), human melanocytes (HEMAc), and human screening UV absorption properties of twelve lichens

© 2015 Wiley Periodicals, Inc. 11


Natural products as photoprotection . N Saewan & A Jimtaisong

using high-performance thin-layer chromatography. Acknowledgment


Among all lichens, the compounds absorbing UVA or
The authors are grateful to Mae Fah Luang University,
UVB ranges were found in Diploicia canescens. After
Chiangrai, Thailand for supporting of this manuscript
phytochemical investigation of this lichen, five depsi-
preparation.
dones (diploicin, dechlorodiploicin, 4-O-methyldiploicin,
O-ethyldechlorodiploicin, and scensidin), one dipheny-
lether (buellin), and two bisxanthones (secalonic acids
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