Summary

Long-term exposure to UV radiation leads to skin ageing and may initiate carcinogenesis. In both cases immunosuppressive activity of UV radiation plays an important role. The aim of the study is to present polyphenols commonly seen in flora and their properties protecting the skin from the damaging influence of UV rays. Polyphenols are a group of compounds which are present in plants. Their common features are: the ring structure of a molecule, hydroxyl groups in the rings and a conjugated double bond system. Such structure makes polyphenols active antioxidants. They also demonstrate anti-immuno­suppressive properties.

Key words:UV • skin • polyphenols • antioxidants • anti-immunosuppression • polyphenols • UV radiation• flavonoids • phenolic acids • immunosuppression

Long-term exposure to UV radiation leads to skin ageing and may initiate carcinogenesis. In both cases immuno­suppressive activity of UV radiation plays an important role [4,12,13,29].

In physiological conditions, in cell mitochondria, a pro­cess of oxidative phosphorylation takes place. As a con­sequence, a certain number of reactive oxygen species (ROS) appear. They are deactivated by mechanisms of antioxidative barrier. UV radiation considerably en­hances generation of ROS. They, in turn, increase se­cretion of the cytokine interleukin 10 (IL-10), which is characterized by strong immunosuppressive activity [2,23,29].

ROS can also damage tissues and DNA structure as well as enhancing migration of Langerhans cells from the epider­mis to the dermis and then to surrounding lymph nodes. It contributes to a decrease in the number of Langerhans cells in the epidermis, which leads to local immunosup­pression. That condition may be directly connected with skin carcinogenesis [3,6,13,24,25].

In order to prevent any potential UV radiation-induced changes, the skin develops self-repair mechanisms, i.e. pigmentation and absorption of UV radiation by mela­nocytes or removal of damaged fragments of DNA by particular enzymes. Applying sun protection filters, ab­sorbing or reflecting UV radiation, is not usually suf­ficient protection against UVA radiation, which also contributes to the development of free radicals as it penetrates to deeper layers of the skin than UVB radia­tion [13,14].

Therefore, scientists are constantly trying to create new, more effective compounds which can be administered not only topically but also systemically. The aim of the study is to present polyphenols commonly seen in flora and their properties protecting the skin from the harm­ful influence of UV rays.

Absorption of UV radiation by skin chromophores leads to excitation, ionization and disintegration of cells and de­velopment of free radicals. UV radiation also contributes to breaking down of oxygen molecules (a radical which has paramagnetic properties) into atomic oxygen, which having reacted with other oxygen molecules turns into a molecule of ozone, O₃. It is a substrate in reactions which result in forming ROS such as singlet oxygen, but it also is a strong oxidant [30].

Some chemical compounds, called photosensitizers, can intensify ROS generation. Such structures are ca­pable of absorbing ultraviolet radiation, which leads to the occurrence of adverse skin reactions (phototoxic and photoallergic reactions). Both cell metabolites (en­dogenous photosensitizers) and substances which are externally applied (exogenous photosensitizers) can serve as photosensitizers. Substances from the other group can be found in some herbs (e.g. in St. John’s wort (Hypericum)), cosmetics (e.g. perfumes) and drugs (e.g. hormonal).

A highly reactive and excited state of the photosensiti­zer molecule can undergo single-electron reduction. The reduced photosensitizer molecule reacts with an oxygen molecule, becomes oxidized and forms a superoxide anion radical. The superoxide anion radical, in the course of further modifications, might be a source of other reacti­ve oxygen species.

The excited photosensitizer molecule in a triplet state (with unpaired electrons) can react with oxygen whose basic state is also a triplet state. As a result of this reac­tion two molecules in a singlet state, including singlet oxygen, are formed.

Usually, during the exposure to UV radiation, ozone, a superoxide anion radical and singlet oxygen appear si­multaneously [22].

Polyphenols are a group of compounds which are present in plants. Their common features are: the ring structure of a molecule, hydroxyl groups in the rings and a conju­gated double bond system. Such structure makes poly­phenols active antioxidants. The compounds easily beco­me oxidized and they turn into quinones. Intermediate forms are highly reactive phenoxyl radicals, stabilized by delocalization of unpaired electrons in the aromatic ring [8,21].

Natural polyphenols are substances which are characte­rized by reducing properties. These properties protect lipids in intracellular cements from oxidation and posi­tively influence collagen synthesis [21]. They also bind free radicals, starting with, among others, hydroxyl ra­dicals and superoxide anion radicals and finishing with lipid radicals. They can stabilize or delocalize an unpa­ired electron or modify ROS into less reactive systems, by hydrogenating or complexing them. These substances often serve as agents chelating metal ions of enzymes ca­talyzing oxidation reactions, oxidase inhibitors or termi­nants breaking radical chain reactions. In the dermis the substances influence the condition of blood vessels and stimulate skin microcirculation. They are natural filters protecting against solar rays, especially UVA rays, which damage the dermis [19,21].

Polyphenols, including phenolic acid (benzoic and cin­namic acid) derivatives and flavonoids, demonstrate an­tioxidative properties.

Ferulic and caffeic acids as well as their derivatives make up the most important phenolic acids which act as antio­xidants. They are compounds whose structure is compo­sed of an aromatic ring and hydroxyl and carboxyl groups. A different level of antioxidative activity of phenolic acids results from their chemical structure and depends on the number and position of hydroxyl groups. The presented properties are enhanced if esterification of particular hydroxyl groups takes place. Caffeic acid, which is a di­hydroxy acid, demonstrates antioxidative properties that are comparable to those of monohydroxy ferulic acid. The activity of the latter is enhanced by an electron-donating (methoxy) group in the ortho position in comparison to a hydroxyl group.

The presented phenolic acids are often called inhibitors of neoplastic diseases. Great amounts of these substances can be found in many plants, e.g. coneflower (Echinacea) or Polypodium leucotomos. They efficiently bind radical oxygen, and neutralize superoxide anion radical, hydro­xyl radical and singlet oxygen which are induced by UV radiation. In that way they inhibit the course of free ra­dical reaction, prevent the process of skin ageing and development of neoplasms [5,15,16,28].

ROS contribute to intermolecular cross-link formation of collagen III. It loses its water solubility and elasticity. The skin loses its firmness, which results in the forma­tion of wrinkles. Phenolic acids protect collagen against degradation by accelerating regeneration of cells. They are therefore used as agents against photodamage of the skin induced by UVA and UVB radiation.

Moreover, ferulic and caffeic acids inhibit glutathione (GSH) oxidation and generation of its oxidized form, glu­tathione disulfide (GSSG), which forms in the reaction of GSH and hydrogen peroxide. Thanks to that it is possible to maintain quantitative balance between these substan­ces in the body. Glutathione disulfide is a dangerous sub­stance for a cell as it might lead to protein deactivation. The thiol group of GSH readily reacts with free radicals of organic substances, which leads to the repair of damaged molecules and formation of a free radical of glutathio­ne. The main function of GSH is to maintain a reduced number of protein thiol groups and maintain functional activity of these structures [16,17].

Additionally, phenolic acids prevent Langerhans cells from migrating from the epidermis to neighbouring lymph nodes, and thus they provide an immunoprotec­tive effect. They also prevent morphological changes to Langerhans cells, such as the loss of dendritic processes or granular atrophy [1,16,26].

Another polyphenol group which is characterized by hi­ghly antioxidative properties, and therefore anti-immu­nosuppressive ones, is the flavonoids. Their molecule con­sists of two benzene rings (A and B), between which there is a heterocyclic ring of pyran or pyrone (C).

In molecules of the majority of natural flavonoids ring A contains two hydroxyl groups at positions 5 and 7 and ring B contains a hydroxyl group at position 3 (catechol group). In a flavonoid molecule at the carbon atom at position 2 of the heterocyclic ring there is usually a hy­droxyl group or phenyl substituent. In isoflavonoids they are located at the carbon atom at position 3.

The level of antioxidative activity of flavonoids depends on the number and location of hydroxyl groups. A large number of hydroxyl groups may enhance that activity. Two OH groups in ring B in the ortho position and one hydroxyl group at position 5′ appear to be of high im­portance. Hydroxylation of benzene rings at positions 5 and 7 might decrease the antioxidative properties of flavonoid.

A methoxy group in a flavonoid molecule, because of its size and blocking a hydroxyl group, decreases antioxida­tive properties of the compound. Some findings indicate that methylation of the hydroxyl group of C7 carbon atom in isoflavonoids does not reduce the ability to inhibit the peroxidation process.

In plants flavonoids take the form of saccharides. A sac­charide residue is usually bound to the carbon atom at position 3 or 7. Owing to the blockage of hydroxyl groups by the sugar residue, glycosides show weaker antioxidati­ve properties in comparison to corresponding aglycones. Differences in antioxidative properties also depend on the kind of saccharide residue present in the molecule.

Glycosidation of the hydroxyl group at the carbon atom at position 3 of the monosaccharide molecule does not reduce the antioxidative capability of flavonoids; antio­xidative activity is significantly lower than in the case of glycosidation with a disaccharide residue.

Antioxidative activity of flavonoids includes the inhibi­tion of enzymes responsible for producing superoxide anion radicals (such as xanthine oxidase, protein kinase C), decrease in the activity needed to generate the su­peroxide anion radical of membrane NADPH oxidase, chelating transition metals, „scavenging” free radicals and stimulation and protection of other antioxidative factors.

Flavonoids not only inhibit the generation of ROS but also deactivate already existing oxygen radicals. Becau­se of their low redox potential flavonoids are thermo­dynamically capable of reducing most free radicals by donating a proton:

The radical which comes from a flavonoid molecule (FL-O.) reacts with another similar radical and forms a quinone structure. Superoxide anion radical, sin­glet oxygen, hydroxyl radical and lipid radicals are the easiest to capture. Neutralizing superoxide anion radi­cal and singlet oxygen leads to turning flavonoids into stable products. Capture of other radicals results in the formation of unstable products which undergo further radical reactions. Reaction of flavonoids with a hydro­xyl radical, readily reacting with aromatic compounds, is particularly effective. Catechins, which constitute one group of flavonoid compounds, demonstrate an ability to capture hydrogen peroxide and superoxide anion radical.

Iron and copper ions enhance the development of ROS by the reduction of hydrogen peroxide and generation of hydroxyl radicals or by catalyzing oxidation of low­-density lipoproteins (LDL).

By chelating transition metals ions, including iron and copper ions, flavonoids play an important role in oxygen metabolism [7].

Various kinds of flavonoids, which act as photoprotec­tive antioxidants, can be found in many plant extracts. These substances prevent, or at least reduce, negative effects of UVA and UVB radiation, including damage to DNA (e.g. fragmentation) and mtDNA structure. They also reduce the development of pyrimidine dimers, ke­ratinocyte apoptosis or gene mutations. They do not allow UV radiation to initiate isomerization of uroca­nic acid. Urocanic acid is an endogenous substance, a histidine derivative, which in the horny layer of the epidermis appears in a slightly soluble trans form and in that form is a main component that absorbs UV ra­diation. After absorption the component undergoes isomerization, which results in the formation of a re­adily soluble cis form. This form acts immunosuppres­sively and inhibits the antigen presentation process by Langerhans cells. The cis isomer does not only act topically. It is also spread throughout the body and it leads to systemic immunosuppression by reducing the number of T lymphocytes and making the processes connected with antigen presentation less intensive. Such processes may lead to increased exposure to in­fections and carcinogenesis. On the other hand, the cis form influences epithelial cells of blood vessels and reduces TNF-α secretion, which has a direct effect on Langerhans cells. TNF-α is a factor attracting Langer­hans cells. Decrease of the amount of this factor leads to a decrease in the number of Langerhans cells and weakening of processes of antigen presentation. It was scientifically proved that long-term exposure to UVB radiation results in thymus atrophy and thus systemic immunosuppression [13,20,23].

Application of cosmetic products having extracts of gre­en tea (Camellia sinensis), which contain flavonoids from a catechin group, leads to a decrease in the number of signs of ageing. It was proved that 3% extract from green tea is sufficient protection against photoageing and pho­toimmunosuppression, owing to the fact that it prevents the reduction of the number of Langerhans cells in the epidermis [9,10,13,18,27,29,31].

Another interesting flavonoid is silymarin, found in milk thistle (Silybum marianum). It contains the isomers sily­bin, isosilybin, dihydrosilybin, silydianin and silychristin. These compounds have been proven to inhibit photocar­cinogenesis by a decrease in oxidative stress and „repair” the damage to DNA induced by UV radiation. If such repa­ir is possible, silymarin prevents apoptosis of keratinocy­tes and fibroblasts which contain the damaged fragment of DNA. The number of pyrimidine dimers is reduced, too. The dimers are molecules formed as a consequence of DNA damage. They exert an immunosuppressive effect and even a carcinogenic effect [11,18].

Researchers constantly attempt to counteract the harm­ful effects of UV radiation. The methods implemented so far do not fully protect the skin against antioxidative and immunosuppressive processes. Sun protection filters do not appear to be entirely effective. Other findings indicate that even preparations with a maximum sun protection factor (SPF) will not help to avoid carcinogenesis. Bearing all this in mind, researchers are constantly seeking plants that contain compounds from polyphenol groups and that demonstrate antioxidative and anti-immunosuppressive properties. There are also attempts to find some ways of relieving signs of ageing.

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The authors have no potential conflicts of interest to declare.

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