Skin Health Properties of Lycopene and Melatonin

Page 26 of 29 Skin Health Properties of Lycopene and Melatonin Lourdes Franco1*, Ana M Marchena2, Ana B Rodríguez2 1Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Medicine, University of Extremadura, Badajoz, Spain. 2Department of Physiology (Neuroimmunophysiology and Chrononutrition Research Group), Faculty of Science, University of Extremadura, Badajoz, Spain.


Review
Skin plays an important role in the thermoregulation of the body, as it regulates the interchange of water and electrolytes with the environment 1 . It also acts as a barrier: a physical filter that absorbs ultraviolet (UV) radiation, a mechanical anti-trauma obstacle and a biological hurdle against microorganisms 2 UV radiation is a strong component that is capable of generating ROS at the skin level. There are several types of ROS and their generation depends on the UV wavelength. Type B UV radiation produces the production of O2 a by activating NADPH oxidase and respiratory chain reactions, while type A UV radiation produces O2 a because it performs a photosensitizing reaction with internal chromophores such as riboflareactio porphyrin 3 . In a specific cell type, ROS stimulates cell growth. A high level of superoxide anion is required for phorbol ester-induced tumor promotion. Various external stress-inducing stimuli (eg, UV radiation, vanadate, and silica) lead to the release of ROS in cells, resulting in the activation of AP-1 via the MAP kinase pathway 4 . Furthermore, photoaging, i.e. aging induced by UV radiation exposure, depends primarily on the degree of sun exposure and skin pigment. People who do not have an outdoor lifestyle, but live in sunny climates have less melanin. In consequence, they will experience a greater degree of photoaging 5 .
However, skin can be damaged; it suffers from progressive morphologic and physiologic disorders with time. The factors causing skin damage can be environmental due to the fact that it is constantly exposed to air, solar radiation and other environmental agents. Mechanical and chemical damage can induce the generation of free radicals and reactive oxygen species (ROS), leading to an imbalance in favour of pro-oxidant systems causing oxidative stress with pathological implications 5 .
The above-mentioned free radicals are chemical species possessing an unpaired electron that can be considered as fragments of molecules which are generally highly reactive. They are continuously produced in cells either as accidental by-products of metabolism or deliberately during phagocytosis, for example. Oxygen and its radical derivatives are some of the most harmful chemical reagents in terms of the damage they can produce in aerobic cells 1 .
Thus, in a person´s daily life, their skin is constantly being damaged by reactive species derived from endogenous processes, as well as environmental agents. This damage is repaired by cellular mechanisms, but if the frequency of injurious events surpasses the rate of repair, damage may turn into permanent and irreversible 1,2 . One of the most damaging environmental factors for the integrity of the skin, as hinted above, is UV radiation, which promotes skin aging, as it leads to formation of free radicals, which ultimately causes a loss of skin elasticity and reduces the ability of the skin to retain water 6 . Therefore, avoiding sun exposure and making use of sunscreen reduces the risk of cancer and skin aging.
Not only does skin reveal the signs of aging caused over time, but also the physiological aging due to environmental factors. Dryness, irregular pigmentation, redness appearance, loss of elasticity and deep wrinkles are some of the visible signs on aged skin. During the last years, substantial progress has been made in understanding cellular and molecular mechanisms that bring about chronological aging and photoaging. The latest research reveals that chronological aging and photoaging share fundamental molecular pathways 5,7 .
As it is known, the exogenous antioxidants are substances contained in food that favor the oxidationreduction reactions balance in cell metabolism. Among these, there are three phytochemicals widely mentioned in the literature: carotenoid lycopen, resveratrol stilbene and vitamin C. The chemical structure of carotenoids determines their physical properties, chemical reactivity and biological activity; on the other hand, their nine or more conjugated bonds make them function as efficient ROS scavengers 8 . Lycopen is typically found in tomato, as well as other red fruits and nutritional supplements 9 .
The skin dermal extra-cellular matrix consists of collagen type I and III, hyaluronan and chondroitin dermatan sulfate as major components. Among them, chondroitin dermatan sulfate appeared to be a possible marker for the tissue fibrosis, which is a characteristic of the photodamage acid has both radical scavenging activity and iron chelating activity. Reactive oxygen species are thought to be associated with the wrinkling due to photodamages of the skin induced by exposure to UV irradiation. Especially the hydroxyl radical is very damaging to a variety of biological substances 10 .
Since the effectiveness of endogenous antioxidant systems decreases during aging, the exogenous supplementation of antioxidants, both from dietary intake and topical application, might be a protective strategy against age-associated skin oxidative damage 4 . This, together with the fact that life expectancy has increased to unexpected limits and, therefore, more and more people are concerned about their appearance and looking younger, has brought a revolution in the current cosmetic industry.
The latest cosmetic generation combines natural or synthetic antioxidants with innovative formulae 11 . Most promising topical treatments for skin aging prevention include herbal extracts, vitamins and antioxidants food supplement, which have been widely accepted to scavenge free radicals from skin cells and to restore skin conditions. The studies about development of cosmetic products against skin aging involve making use of antioxidant substances capable to prevent and treat skin damage 12,13 .
Melatonin is produced mainly by pinealocytes in the pineal gland, which is located in the medline of the brain, just above the posterior commissure at the dorsal ventricle. Is also produced by neuroendocrine cells in the retinan harderian glands, gastrointestinal tract and pancreas edge of the third ventricle 14 and the cosmetic industry tests a large number of this substance with sunscreen properties 15 . Among these substances, we find melatonin and lycopene 16 , which showed a clearly efficacy in the improvement of skin elasticity and pronounced hydration effects on human skin. Lycopene is an effective antioxidant, and this is clearly a major important mechanism of lycopene action. In that sense, lycopene can trap singlet oxygen and reduce mutagenesis in the Ames test. Evidence is accumulating for other mechanisms as well. Lycopene in physiological concentrations is capable of inhibiting the growth of human cancer cells because it interferes with the signals of the growth factor receptor and the cell cycle in prostate cancer cells without evidence of toxic effects or apoptosis of the cells 17 . The hormone melatonin is a highly conserved molecule, it has a crucial role in the maintenance of the skin. As the skin has functional melatonin receptors and also acts as a complete system capable of producing and regulating melatonin synthesis, melatonin is a promising candidate for its maintenance and protection 18 . Physiologically, the best known role of melatonin is that of a chronobiotic factor or zeitgeber, which is capable of regulating the oscillations of the internal biological clock. It is thought to act in the control of seasonal and circadian rhythms. This is based on the fact that melatonin secretion is related to ambient light and normally exhibits a strictly regulated diurnal pattern. In this sense, melatonin is sometimes called "the hormone of darkness" 14 .
Firstly, melatonin is a hormone synthesized mainly by the pineal glandule. It is also produced in other parts of the body, like by chromaffin cells in the intestines. The main function of melatonin in the body involves the control of circadian and seasonal rhythms 19 , but it is also implicated in skin functions, such as hair growth cycling or fur pigmentation and has an important role in melanoma control [20][21][22][23] . Many studies report anti-oxidative properties of melatonin as a free radical scavenger 24,25 , due to the fact that it suppresses ultraviolet (UV)-induced damage to skin cells and shows strong antioxidant activity in UV exposed cells 26 . Melatonin could neutralize environmental or internal stresses to preserve the integrity of the organism and to maintain its homeostasis 27 . Melatonin increased collagen accumulation in the cultures molecular mechanism of melatonin promotion of self-renewal of NSCs in which a chain reaction in the ERK and TGF-β/ Smad pathways promotes self-renewal and transcription of nestin 28 . Tamura H et al. 29 , reported that melatonin has an important function in the complex endogenous control of HF biology, not only as an antioxidant function, but also inhibit keratinocyte apoptosis in the short-term on mice skin 30 .
Secondly, lycopene is a pigment from carotenoids family that lacks provitamin A activity; however, it has potent antioxidant properties 31 . It is responsible for the red colour in several fruits and vegetables, such as tomato or watermelon, and it is also synthesized by some microorganisms. Some studies have shown that lycopene has anticancer properties against certain tumours like colon, prostate, lung or breast [32][33][34] . Moreover, its chemopreventive effects against photo-induced tumours in mice models have also been reported. In other studies, topical application of lycopene before UV radiation exposure reduced photodamage in a dose-dependent relationship 35,36 . Most of the reported health benefits of lycopene are attributed to its ability to protect cells against oxidative damage. Despite the fact that the amount of research focused on lycopene has not been as large as that focused on other carotenoids, on in-vitro studies lycopene appears to be a very efficient quencher of singlet oxygen and a potent scavenger of oxygen radicals 37,38 . The chemopreventive effect of lycopene against photoinduced cell damage has been proved in several studies. For this reason, this carotenoid is already included in diets and numerous dermatological products [39][40][41] .
Some studies reported the benefits of consuming virgin lycopene-enriched olive oil for the antioxidant capacity 11,41 , highlighting how this compound could be a valuable tool to have in mind. Therefore, including lycopene in our daily intake could be a good way for health promotion against multiple disorders in which oxidative stress plays an important function. Adding up, lycopene is being widely employed in cosmetic formulations due to its protective properties against photodamage and skin aging 24 .
As for melatonin, also known chemically as N-acetyl-5-methoxytryptamine, it is a natural compound found in animals, plants and microorganisms. In humans, melatonin signal forms part of the system that regulates the circadian rhythm and the sleep-wake cycle by chemically causing drowsiness and lowering the body temperature 25,26 . Besides its function as a synchronizer of the biological clock, melatonin also exerts a powerful antioxidant activity. Melatonin is implicated in skin functions such as hair growth cycling, fur pigmentation, melanoma control. Melatonin receptors are expressed in several skin cells including normal and malignant. It is also able to suppress ultraviolet induced damage to skin cells and shows strong antioxidant activity in UV exposed cells. The evidence suggests that melatonin could be a significant contributor to regulation of the local system that preserves the physical and functional integrity of the skin 19 .
In another study, Franco said the resveratrol treatment can prevented the increase in oxo8dG induced by KBrO3, with the resveratrol treatment and the control group. The antioxidants melatonin and vitamin E and the spintrapping compound PBN also decreased the level ofoxo8dG in the kidney with respect to the KBrO3 group, although the protection was partial in this case since oxo8dG was significantly lower than in the KBrO3 group, but it was still significantly higher than in the control group 42 .
In the study conducted by Marchena, a cream was formulated containing both antioxidants under study in a separate manner. The results show us that the cream significantly increases the stratum corneum elasticity and enhances the hydration conditions of the skin after the 8-week period application, when compared with the control values. The formulation containing lycopene increased pigmentation index values, so it seems to be an excellent tool to avoid skin photodamage due to its photoprotective effect on skin 16 .
According to the results obtained by Marchena, it can be concluded that melatonin and lycopene could be used as effective antioxidant agents, and they should be considered in the formulation of skincare products to avoid skin aging and promote skin appearance 16,43 .
In this sense, antioxidant cosmetics including melatonin and lycopene could be employed as useful products in formulations for hydration, protective and antiaging purposes 44,45 .