NATURAL PHENOLICS IN THE PREVENTION OF UV-INDUCED SKIN DAMAGE. A REVIEW

UV skin exposure induces extensive generation of reactive oxygen species (ROS). These can react with DNA, proteins, fatty acids and saccharides causing oxidative damage. Such injuries result in a number of harmful effects: disturbed cell metabolism, morphological and ultrastructural changes, attack on the regulation pathways and, alterations in the differentiation, proliferation and apoptosis of skin cells. These processes can lead to photoaging and skin cancer development. One approach to protecting human skin against the harmful effects of UV irradiation is to use antioxidants as photoprotectives. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. In this review, we strive to summarize the findings of studies performed to date, regarding the photoprotective effects of plant phenolics on the skin damage induced by UV radiation.


INTRODUCTION
In recent years, the incidence of various diseases and disorders related to solar ultraviolet radiation has increased alarmingly and continues to grow.Chronic exposure of mammalian skin to UV radiation induces a number of biological responses, including development of erythema, edema, sunburn cell formation, hyperplasia, immune suppression, DNA damage, photoaging and melanogenesis.These alterations are directly or indirectly involved in the development of skin cancer [1][2][3] .
UV radiation is a very potent initiator of photochemical reactions through excitation of electrons and this can result in energy transfer or chemical modification of the exposed molecule.After absorbing the UV light, the molecule may become damaged and affect other molecules, e.g. by producing reactive oxygen species (ROS).In biological systems, the absorbed light can interact with endogenous photosensitive molecules or/and with exogenous photosenzitizers originating from drugs or cosmetic ingredients.Consequently, these interactions can directly or indirectly produce deleterious, cytotoxic and genotoxic effects 4 .

UV RADIATION AND ITS EFFECTS ON THE SKIN
UV radiation forms a part of the electromagnetic spectrum with wavelengths between 200 nm and 400 nm.It is divided into three categories dependent on wavelength, long wave UVA (320-400 nm), medium wave UVB (280-320 nm), and short wave UVC (200-280 nm) [5][6][7] .
Between 1970 and 1987, substantial damage to the protective ozone layer resulted in an increased amount of UV radiation reaching the earth's surface 7 .
Of this, more than 90 % of solar radiation that reaches us is UVA.This longer wavelength, considered as the "aging ray" penetrates deep into the epidermis and dermis of the skin.Compared to UVB, UVA is about 1000 times more effective in the production of an immediate tanning effect which is caused by darkening of the melanin in the epidermis.Intense or extensive exposure to UVA can burn sensitive skin, and if prolonged, it can damage underlying structures in the corium and cause premature photoaging of the skin.It mainly causes skin sagging rather than wrinkling and it may suppress some immunological functions.UVA-induced responses in cells happen mainly because of oxidative processes initiated by endogenous photosensitization.After UVA exposure, singlet oxygen, H 2 O 2 and hydroxyl free radicals are generated.These can cause damage to cellular proteins, lipids, and saccharides.UVA injury tends to cause necrosis of endothelial cells, thus damaging the dermal blood vessels.UVA can produce structural damage to the DNA, impair the immune system, and lead to cancer.It has been linked to 67 % of malignant melanoma 2,6,8,9 .
UVB radiation is regarded as the "burning ray" and it makes up 4 to 5 % of UV light.UVB is a minor but the most active constituent of solar light.UVB is 1000 times more capable of causing sunburn than UVA.UVB is also more genotoxic than UVA.UVB acts mainly in the epidermal basal cell layer of the skin.It induces direct and indirect adverse biological effects, including the formation of pyrimidine photoproducts, isomerization of trans-to cis-urocanic acid, induction of ornithine decarboxylase activity, stimulation of DNA synthesis, free radical production in the skin, cell cycle growth arrest, photoaging and photocarcinogenesis.It significantly decreases antioxidants in the skin, impairing the skin's ability to protect itself against the free radicals generated by exposure to sunlight.It is considered to be responsible for inducing skin cancer (squamous and basal cell carcinoma) due to DNA damage.It is also suspected of lowering the skin's immune defense system 4,6,8,9 .
UVC is very dangerous to all forms of life, even with only very short exposures.It is extremely damaging to the skin.Fortunately, UVC radiation from the sun is completely absorbed by molecular oxygen and ozone in the earth's atmosphere and no solar radiation of wavelengths below 290 nm reaches the surface of the earth 4,6 .
To exert its biological effects, UV must be first absorbed by cellular chromophore, which transforms the energy into a biochemical signal.Subsequent photobiochemical reactions provoke changes in cell and tissue biology resulting in increased photoaging and skin cancer occurrence.Nucleic acids and proteins are the major cellular chromophores absorbing radiation in the UVB wavelength range.If DNA absorbs energy within the UVB region of the spectrum this may result in DNA lesions.The main lesions induced by UVB are cyclobutane-pyrimidine dimers and pyrimidine-pyrimidone photoproducts.Blockade of RNA transcription that occurs as a result of DNA photoproduct formation leads to activation of the p53 protein that induces apoptosis of irradiated keratinocytes.Repair of photolesions is the primary response to DNA photodamage in surviving cells.However, if the damage persists into the S phase of the cell cycle, other repair mechanisms might lead to mutagenesis resulting mainly in characteristic cytosine to thymine substitution.When such mutations occur in the p53 gene, keratinocytes lose their ability to undergo the apoptotic process following high-dose UV exposure.Tryptophan and tyrosine are the main amino acids that absorb UVB.Other biomolecules, acting as radiation absorbents within the UVB range, are NADH, quinones, flavins, porphyrins, 7-dehydrocholesterol, and urocanic acid 6,9,10 .UVA-absorbing cellular molecules in the initiation of UVA-induced photosensitization are still largely unknown, only transurocanic acid was reported 9 .
Damage to skin epidermal cells becomes evident as early as 2 h after UV irradiation.The initial indicator of damage is a decrease in keratinosomes, which results in the formation of dyskeratotic cells.Intracellular edema can be seen 16-18 h after exposure, followed at 30-48 h by intercellular edema that develops around damaged keratinocytes 6 .The sunburn cells were proposed as one of the earliest examples of apoptosis.UV-induced apoptotic cells are rapidly phagocytized by the surrounding keratinocytes.Macrophages are also known to bind and phagocytize apoptotic cells and their number in the skin increases dramatically after UVB treatment 6 .
The degenerative changes in keratinocytes include mitochondrial swelling and rupture, condensation of the cytoplasm and the appearance of pyknotic nuclei.The observed cellular damage is maximal at 48-72 h for the total UV range 6 .
UV exposure to the skin results in generation of reactive oxygen species 11,12 .ROS are constantly generated in keratinocytes and fibroblasts, and are rapidly removed by nonenzymic and enzymic antioxidant substances.These prevent harmful effects of ROS and maintain a prooxidant/antioxidant balance, thus resulting in cell and tissue stabilization.ROS comprise a number of active metabolites including hydroxyl radical, superoxide anion and peroxyl radical and their active precursors namely singlet oxygen, hydrogenperoxide and ozone.Nitric oxide and nitric dioxide, reactive nitrogen species (RNS), are also generated.Excess of free radicals results in a cascade of events mediating progressive deterioration of cellular structure and function, and this can lead to a loss of cellular integrity by modification of DNA and also to abnormal expression of cellular genes.UV-generated ROS affect mitogen-activated protein kinase (MAPK) signalling cascades.These have been shown to activate nuclear factor kappa B (NF-κB), as well as c-Jun N-terminal and p38 MAP kinases followed by activation of transcription factor AP-1 (activation protein 1).Both may contribute to the induction of heme oxygenase-1 (HO-1) and matrix metalloproteinases (MMPs) in the skin.Increased level of HO-1 may elevate cellular levels of iron that can promote further ROS generation.MMPs induction leads to enhanced degradation of extracellular matrix proteins that favor wrinkle formation and metastases.ROS damage cell membranes by peroxidation of fatty acids within the phospholipid structure of the membrane.During this process, lipid peroxide radicals, lipid hydroperoxides and other fragmentation products, that are themselves active oxidizing agents, are formed.The lipid peroxides are comparatively longer-lived species and can initiate the chain reactions that enhance oxidative damage 12 .
Although the skin possesses an elaborate antioxidant system to deal with the UV-induced oxidative stress, extensive and chronic exposure to UV can exceed the cutaneous antioxidant capacity, leading to oxidative damage that may result in skin disorders, immunosuppression and premature skin aging 13 .
One approach to protecting humans from the harmful effects of UV irradiation is to use active photoprotectives.In recent years, naturally occurring compounds have gained considerable attention as protective agents.Vitamins C, E, and β-carotene have been incorporated into many skin care products for instance.Another approach is afforded by the antioxidative properties of phenolics.These substances can be used as ingredients in human diet or added to preparations for topical application 1,5,8 .
The three important groups for humans are phenolic acids, flavonoids, and high-molecular weight polyphenols 22,23 .Naturally occurring phenolic acids contain two distinguishing constitutive carbon frameworks: the hydroxycinnamic and hydroxybenzoic acid structures 22 .The flavonoids consist of a large group of low-molecular weight polyphenolic substances, benzo-γ-pyrone derivatives that are diverse in chemical structure.High-molecular weight polyphenols, commonly known as tannins, are polymer compounds.They are divided into two groups: condensed (polymers of catechines or epicatechines) and hydrolysable (polymers of gallic or ellagic acids) 23 .The phenolics, particularly polyphenols exhibit a wide variety of beneficial biological activities in mammals, including antiviral, antibacterial, immune-stimulating, antiallergic, antihypertensive, antiischemic, antiarrhytmic, antithrombotic, hypocholesterolemic, antilipoperoxidant, hepatoprotective, anti-inflammatory, and anti-carcinogenic actions.They are powerful antioxidants in vitro 14,18,19,[24][25][26][27] .In a structure-dependent manner, flavonoids and phenolic acids are capable of scavenging ROS, RNS and chelating transition metal ions such as iron and copper, which play vital roles in the initiation of free radical reactions 19,[28][29][30] .Several studies have shown the flavonoids to act as scavengers of superoxide anions, singlet oxygen, hydroxyl radicals, and lipid peroxyl radicals 31,32 .There are also reports of flavonoids inhibiting the activities of many enzymes, including lipoxygenase, cyclooxygenase, monooxygenase, xantinoxidase, mitochondrial succinate dehydrogenase and NADH-oxidase, phospholipase A 2 , protein kinases, and nuclear transcription factor (NF-κB) 33,34 .
Phenolics are believed to be capable of acting in redoxsensitive signalling cascades to inhibit DNA damage 19 .In contrast to their beneficial effect, some phenolics however have also been found in vitro to be mutagenic.These harmful effects are suspected to result from the prooxidant rather than antioxidant action of these compounds.Therefore it is necessary to investigate their toxic effects before human use 33 .
In the past decade, the antioxidant activity of herbal phenolics, namely phenolic acids and flavonoids has been given much attention.Many flavonoids such as quercetin, luteolin and catechins are better antioxidants than the nutrients vitamin C, vitamin E and β-carotene 25 .Therefore, the phenolics may be beneficial in preventing UV-induced oxygen free radical generation and lipid peroxidation, i.e. events involved in pathological states such as photoaging and skin cancer.
This review is a summary of the findings of the photoprotective effects of some naturally occurring herbal polyphenols and phenolic rich extracts in studies of the skin damage induced by UV irradiation.
These two acids have been demonstrated to protect phospholipidic membranes from UV-induced peroxidation by inhibiting propagation of the lipid peroxidative chain reaction and to react with nitrogen oxides 36 .Caffeic acid and, at a greater degree, ferulic acid proved effective in protecting human skin from UVB-induced erythema.Ferulic acid, shown to be a strong UV absorber, is employed as a photoprotective agent in a number of skin lotions and sunscreens 37 .
As a powerful antioxidant and metal ion chelator, quercetin is believed capable of preventing the harmful effects of UV light or at least of reducing the damage 38 .Inal et al. showed that quercetin protected skin antioxidant systems, namely glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase activities, against UVA irradiating damage in rats to a considerable degree 11 .Oral intake of quercetin prevented UVB-induced immunosuppression in SKH-1 hairless mice 39 .In vitro, quercetin and its semisynthetic derivatives (quercetin 3-O-acetate, quercetin 3-O-propionate, quercetin 3-Opalmitate) were found to inhibit UVC radiation-induced peroxidation in liposomal membranes 40 .
Apigenin was found to be effective in the prevention of UVA/B-induced skin carcinogenesis in SKH-1 mice.When applied topically it inhibited UV-mediated induction of ornithine decarboxylase activity, reduced tumour incidence and increased tumour free survival 41,42 .Several studies have provided evidence that apigenin may prevent UV-induced skin tumorigenesis by inhibiting the cell cycle and cyclin-dependent kinases (cdk).Apigenin treatment of mouse keratinocytes induced G2/M cell cycle arrest, accumulation of the p53 tumor suppressor protein and expression of its downstream effector (a cdk inhibitor p21/WAF1) 41 .This arrest was also accompanied by inhibition of p34/cdk2 kinase protein level and activity, which was found independent of p21/WAF1(ref. 8).In human diploid fibroblasts apigenin produced G1 cell-cycle arrest by inhibiting cdk2 kinase activity and inducing p21/WAF1 (ref. 43).hairless mice skin substantially inhibited the UVB-induced H 2 O 2 production, contact hypersensitivity and reduced the inflammatory edema reaction.Equol was the most effective of them 48 .

Genistein
Genistein (5,7,4'-trihydroxyisoflavone) occurs in plants.In particular, it is the major component of soybeans 44 .Genistein is also able to modulate cell cycling and to prevent cancer in many organ systems 45,46 .
Genistein inhibited UVB-induced protooncogene expression and skin tumorigenesis in hairless mice 47 .Topical application of genistein and its gastrointestinal metabolites such as equol, isoequol and dehydroequol to

Resveratrol
Resveratrol (trans-3,5,4'-trihydroxystilbene) is a naturally occurring polyphenolic phytoalexin amply present in the skin and seeds of grapes.Other plant sources include peanuts, red wine and berries 49 .Resveratrol is an effective antioxidant with strong anti-inflammatory and antiproliferative activity.It also shows inhibitory effects on diverse cellular processes associated with tumour initiation, promotion and progression 5,8 .
Topical application of resveratrol to SKH-1 hairless mice resulted in significant inhibition of UVB-induced skin edema.Resveratrol pre-treatment caused a decrease in UVB-induced generation of hydrogen peroxide and infiltration of leukocytes 5 .In addition, topical application of resveratrol substantially reduced UVB-induced lipid peroxidation, cyclooxygenase and ornithine decarboxylase activities, and protein expression of the latter enzyme 50 .In normal human epidermal keratinocytes, resveratrol blocks UVB-mediated activation of NF-κB in a dose-and time-dependent manner 51 .
Nordihydroguaiaretic acid (NDGA) significantly inhibited UVB-induced c-fos and AP-1 transactivation in the HaCaT keratinocyte cell line.In addition, NDGA was found to reduce the activity of phosphatidylinositol 3-kinase which is the UVB-inducible enzyme involved in the expression of AP-1 and its component proteins c-Fos 52 .Natural phenolics in the prevention of UV-induced skin damage.A review

Carnosic acid
This is the major constituent of rosemary (Rosmarinus officinalis) and sage (Salvia officinalis), and it has powerful antioxidant action 53 .Chemoprotective effects against carcinogens have been identified when this acid is tested in animals 54 .
Pretreatment of human fibroblasts with carnosic acid resulted in suppression of metalloproteinase-1 mRNA elevation caused by UVA irradiation 55 .
These polyphenols have been shown to function as anti-inflammatory or anticarcinogenic agents in various biological systems.Of these substances, EGCG has been shown to be the most effective chemoprotective agent against cutaneous inflammatory or carcinogenic responses 63 .
In recent years, a wide range of studies using several tumour bioassay protocols have demonstrated that topical application of polyphenolic fraction isolated from green and black tea show significant chemoprevention effects against each stage of skin carcinogenesis in the mouse skin model 62 .In hairless mice, both chronic oral feeding and topical application of green tea polyphenols (GTP) was found to result in significant protection against UVBinduced cutaneous edema and erythema, lipid peroxidation, depletion of epidermal antioxidant-defence enzyme system and formation of prostaglandin metabolites 13,64 .Using in vitro system, Wei at al. have shown that aqueous extracts of green and black tea scavenge H 2 O 2 and inhibit UV-induced oxidative DNA single strand damage 5,64 .Topical application of GTP prior to UVB irradiation resulted in reduced production of cyclobutane-pyrimidine dimers in epidermis and dermis of human skin.This reduction is probably due to protection of DNA repair enzymes from inactivation by ROS and due to absorption of UV energy by EGCG (I max 270-273 nm) 5 .Green tea polyphenols (GTP) induce apoptosis in human epidermal carcinoma cells and human carcinoma keratinocytes 63 .Recently, topical application of EGCG before exposure has been shown to significantly reduce UVB-induced development of erythema, myeloperoxidase activity, H 2 O 2 and NO production, and epidermal lipid peroxidation in human skin 63,65 .It was also found to block UV-induced leukocyte infiltration.The addition of EGCG to tumour cells results in G0-G1 cell cycle arrest.It has been concluded that GTP may reduce tumour development by arresting transformed cells in the G0-G1 phase and removing them by augmenting apoptosis 65 .

Silymarin
Silymarin is a standardized extract of flavonolignans from the seeds of the milk thistle, Silybum marianum (L.) Gaertner.The main components of silymarin include silybin, silidianin, silychristin and isosilybin.Silybin is considered to be the principal biologically active constituent with regard to its antioxidant and anti-inflammatory properties.Silymarin has been widely used in traditional European medicine for two thousand years, especially for the treatment of liver diseases.Several papers have also reported its skin cancer chemoprotective action 5,[56][57][58] .
Topical application of silymarin was found to result in significant inhibition of UVB-induced skin edema, formation of sunburn and apoptotic cells.It also caused depletion of catalase, induction of cyclooxygenase and ornithine decarboxylase in mouse models 59 .Topical application of silymarin resulted in protection against UVBinduced formation of cyclobutane-pyrimidine dimers in mouse skin 5 .Treatment with silymarin prevented UV-induced infiltration of inflammatory leukocytes, which are responsible for induction of UV-induced oxidative stress in the skin.Application of silymarin to mouse skin also resulted in significant reduction in the number of UVBinduced hydrogen peroxide producing cells and inducible nitric oxide synthase expressing cells 60 .Silymarin showed a dose dependent protective effect against UV-induced damage in human keratinocytes via inhibition of NF-κB activation 61 .cancer and premature aging.HTs and CTs plant samples administered topically or injected intraperitoneally have been shown to reduce H 2 O 2 production, decrease tumor incidence or delay their appearance in the skin of hairless mice.In addition, they inhibit induction of ornithine decarboxylase and stimulation of epidermal DNA synthesis, to a remarkable extent 66,67 .

Tannins
Tannins are polyphenolic compounds widely distributed in the plant kingdom and are believed to provide in plants a chemical defence against predators and ultraviolet radiation.They are classified into two major categories, hydrolysable tannins (HTs) which include gallotannins and ellagotannins, and condensed tannins (CTs), proanthocyanidins 66,67 .
These plant polyphenols are potent antioxidants that may protect against free radical damage caused by exposure to UV light and, in turn, reduce the risk of skin

Capparis spinosa extract
The flower buds of C. spinosa have been used for several purposes since ancient times.These plants are widely distributed in tropical or subtropical as well as arid areas of the world 68 .The major constituents of lyophylized extract of C. spinosa (LECS) have been identified as kaempferol and quercetin derivatives and caffeic, ferulic, p-cumaric, and cinnamic acids.LECS show significant antioxidant effect 69 .
Topically applied LECS reduces UVB-induced skin erythema in healthy human volunteers 69 .

Culcitium reflexum H.B.K. leaf extract
C. reflexum H.B.K is a herbaceous plant grown in South America, especially in Ecuador and Columbia.The local folk used it for the treatment of some skin inflammatory conditions.C. reflexum leaves contain a large amount of phenolic compounds, especially flavonols.The main constituents have been identified as rutin, kaempferol, quercetin and its glucosylated derivates and some cinnamic acid derivates.Ethanolic extract of C. reflexum possesses a strong antioxidant or free radical scavenging effect.
Topical application of C. reflexum extract in the form of a gel has proven to be a significant in vivo protection against UVB-induced skin erythema in healthy human volunteers 70 .
Pycnogenol® has been found to have excellent free radical scavenger properties by enhancing the production Natural phenolics in the prevention of UV-induced skin damage.A review of antioxidative enzymes 72 .It has been found to inhibit UV-induced NF-κB-dependent gene expression in a concentration dependent manner in HaCaT keratinocytes 71 .Topical application of a gel containing pycnogenol significantly prevented UV-induced erythema in rat 73 .Same effect was observed in human after oral intake 71 .

Ginkgo biloba extract
G. biloba extract (EGb 761) is a well-defined product prepared from the green leaves of the G. biloba tree.This is a natural mixture containing flavone glycosides (33 %), mostly quercetin and kaempferol derivatives, and terpenes (6%).In man, EGb 761 is used or experimented on for the treatment of pathologic conditions like stroke, aging, and some drug induced toxicities.It has been demonstrated to stop lipoperoxidation by quenching the peroxyl radical 74,75 .
EGb 761 has been also found to decrease the number of UVB-induced sunburn cells in mice skin 75 .Oral administration of G. biloba extract leads to increased superoxide dismutase activity in UVB-irradiated mice skin 76 .

Grape seed extract
Grapes are one of the most consumed fruits in the world.Grapes are rich in polyphenols and 60-70 % of grape polyphenols are found in grape seeds.Grape seed polyphenols (GSP) include flavan-3-ol derivatives -catechin, epicatechin and oligomeric proanthocyanidins 77 .GSP exert anti-inflammatory, anti-apoptotic, anti-necrotic and anticarcinogenic activities, and have beneficial effects against several diseases, including skin aging and cancer 78 .GSP have been shown to exert a much stronger oxygen free radical scavenging effect than vitamin C and E and to prevent UVB-and UVC-induced lipid peroxidation 77,79 .Dietary feeding of GSP to SKH-1 hairless mice resulted in prevention of UVB-induced photocarcinogenesis in terms of reduced tumor incidence, tumor multiplicity and tumor size.It also resulted in reducing malignant transformation of UVB-induced papillomas to carcinomas 79 .

Krameria triandra root extract
Rhatany, the dried roots of K. triandra Ruiz and Pavon, are used in herbal preparations for a variety of systemic and topical disorders.The extract contains phenolic constituents, low molecular weight neolignans and medium high molecular weight oligomeric proanthocyanidins.
Extract of K. triandra has shown protective effects against UVB-induced photodamage in human keratinocyte cells 80 .

Prunus persica flower extract
The flowers of P. persica have been used for skin disorders in East Asia from ancient times.They contain four kaempferol glycoside derivatives (multiflorin B, trifolin, afzelin, and astragalin) 81 .
P. persica extract has been demonstrated to possess protective activity against UV-induced cytotoxicity in keratinocytes and fibroblasts 82 .It inhibits UVB/ UVCinduced DNA damage and lipid peroxidation in skin fibroblasts 83 and, the quantity of 14C-arachidonic acid/ metabolites released from UVB-irradiated human keratinocytes 81 .Both the extract and multiflorin B inhibit dose dependently UVB-induced erythema formation in guinea pigs when topically applied 81 .The extract was also shown to delay tumour development after UVB-induced skin carcinogenesis in SKH-1 hairless mice.It also reduces UVB-induced ear edema in IRC mice 83 .Sanguisorba officinalis L. root extract S. officinalis L. is found in China, Korea, Japan Siberia and Europe 84 .Hydrolysable tannins are reported as characteristic constituents of S. officinalis roots and are considered to be partially responsible for the therapeutic effects of this crude drug 85 .
Topical application of S. officinalis L. extract following UVB exposure inhibited wrinkle formation, maitained skin elasticity and prevented the decrease of dermal elastic fiber linearity in the rat hind limb skin in a dose dependent manner 86 .

Sedum telephium L. leaf extract
The leaves or fresh juice of S. telephium L. were widely used in antiquity to cure many types of inflammatory skin diseases.S. telephium L. leaves contain polysaccharides, gallic acid, and flavonol glycosides (quercetin and kaempferol).
Gel formulations of both the total lyophilised juice and, to a greater degree, the lyophilised flavonolic fraction appear to possess potent protective effects against UV-induced skin erythema in human volunteers 87 .

CONCLUSION
Human skin is constantly exposed to the UV irradiation present in sunlight.This may induce a number of pathobiological cellular changes.The development of novel preventive and therapeutic strategies depends on our understanding of the molecular mechanism of UVdamage.
Plant phenolics are one candidate for prevention of the adverse effects of UV radiation on the skin and evaluation of their clinical efficacy is awaited.