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SKIN WhiteningGroup VIISkin ColourThe colour of human skin is influenced by both internal and external factors but is primarily due to pigments, is melanin, produced by melanocytes of the basal layer of the dermis.A secondary contributor to skin color is the hemoglobin located in the blood capillaries of the dermis.Although increased epidermal pigmentation results in a darker skin phenotype, there are actually more distinct ultrastructural characteristics that correlate with skin color. Specifically, the distribution of melanosomes in the keratinocytes correlates with skin color. In white skin, melanosomes are small and aggregated in complexes. In black skin, there are larger melanosomes, which are singly distributed within keratinocytes.It appears as a representative of blood perfusion and depends on the amount of oxygenated (red) and deoxygenated (blue) blood which can be influenced by temperature and emotions.2Skin and MelaninSkin is made up of cells which all have the basic structure of a nucleus, which contains the genes, surrounded by cytoplasm, which has a different composition depending on the cell type.The skin pigment melanin is made in specialised cells called melanocytes that remain at the base of the epidermis. Melanin is packaged into tiny bundles called melanosomes, which are transferred to adjacent skin cells, via the melanocytes arm-like projections.Skin and MelaninThese melanosome particles become arranged like an umbrella over the nucleus giving protection to the DNA against ultraviolet rays from the sun.When epidermal cells travel towards the skins surface, they carry their melanin with them, and it remains even after the nucleus is lost. It is this melanin which is mainly responsible for the colour of an individuals skin.MelaninTwo types of melanin are produced, namely eumelanin which is a dark brown/black pigment and pheomelanin which is a lighter reddish/yellow pigment.Changes in the amount of each pigment produced is also under genetic control and the ratio of eu- to pheo-melanin is responsible for variations in both skin and hair colour.Thus the melanocytes of pale-skinned redheads produce lots of pheomelanin, whilst those of people with a range of skin colours from beige to black and with hair from blonde to brown to black produce more eumelanin than pheomelaninA striking variation in skin colour is seen in people with albinism; here small genetic changes that cause an interruption in any one of the many steps that control melanin production result in failure to produce the pigment and the person has extremely pale skin.5MelaninMelanin protects the skin from the harmful rays of sunlight, which is made up of visible and invisible light.It is UVA and UVB that cause damage to the skin, but melanin protects the skin from damage by reflecting and absorbing some of the UV energy.In the absence of melanin, UV energy penetrates deep into the skin where it can cause small amounts of damage to the DNA in the nucleus of the still living epidermal cells.Although small amounts of such damage can be spontaneously fixed by the cells repair machinery, unrepaired, accumulated damage can cause cells to multiply uncontrollably, resulting in skin cancers. People with skins in which there is little or no eumelanin, or which predominantly contain pheomelanin, are all at increased risk of developing skin cancers. Thus people with albinism or very pale skin generally suffer sun-burn easily without tanning when exposed to the sun and are at greatest risk. It is not only the suns rays that damage the skin, sun beds used for salon and home tanning are just as dangerous.6Skin ColourIn areas where UV radiation was highest, peoples skins were darkest and vice versa.UV exposure does not only induce skin cancer but has other consequences which may have contributed to the development of skin colour variation over long periods of time.UV rays are also known to break down folate (vitamin B6) in the blood vessels just beneath the skin.Folate is essential for dividing cells and therefore the developing foetus is most vulnerable to the effects of low folate levels, which is why pregnant women are advised to take folate supplements. A shortage of folate can result in abnormalities of the spine and brain of the baby. It is thought that melanin offers protection from folate damage in the same way that it lessens DNA damage.7Skin WhiteningSkin-whitening products have been widely used in the cosmetic field and clinic therapyWhitening agents, such as hydroquinone, kojic acid, and ascorbic acid derivatives have shown efficacy in a variety of hyperpigmentary disordersThe ideal depigmentating compound should have a potent, rapid, and selective bleaching effect on hyperactivated melanocytes, carry no short- or long-term side effects, and lead to a permanent removal of undesired pigmentThey are supposed to either lighten skin (individuals who wish to change or modify their skin color) or depigment skin (treatment for abnormal-hyperpigmentation skin such as melasma, freckles, and senile lentigines).8DepigmentationThe transcription and activity of tyrosinase, TRP-1, TRP-2, and/or peroxidaseThe uptake and distribution of melanosomes in recipient keratinocytesMelanin and melanosome degradation and turnover of pigmented keratinocytesTRP = Tyrosinase Related Protein9Tyrosinase InhibitionTyrosinase is a copper enzyme, which catalysis both the hydroxylation of monophneols to o-diphenols and the oxidation of o-diquinones to o-quinones.Most whitening agents act spesifically to reduce the function of this enzyme by means the following mechanisms : interference with this transcrription and/or glycosylation, inhibition by different modalities, reduction by products and post-transcriptional controlEx: hydroquinone, kojic acid, azelaic acid, paper extract mulberry, arbutin, licorice extract, ellagic acid10Product Reduction and Reactive Oxygen Species (ROS)Compound with redox properties can have depigmenting effects by interacting with o-quinones, thus avoiding the oxidative polimerative of melanin intermediate or with copper at the active site. Therefore, that melanin cannot be formed by action of tyrosinase until all ascorbic acid is oxidizedEx: ascorbic acid, magnesium L-ascorbyl-2-Phosphate (VC-PMG), thioctic acid, alpha tocopherol11Inhibition of Melanosomes TransferThe activation of protease-activated receptor-2 (PAR2), a seven transmembrane G-protein coupled receptor, which is expressed in keratinocytes and not in melanocytes, was found to activate keratynocytes phagocytosis, enhancing melanosome transferInhibition of Par-2 cleavage by serine protease inhibitor, such us RWJ-50353, completely avoids the UVB-induced pigmentation of epidermal analogsEx : niacinamides, RWJ-50353, soybean tripsin inhibitor,12Skin Turnover AccelerationThe capacity of several compounds to disperse melanin pigment and/or accelerate epidermal turnover can result in skin lighteningTopical apllication has beenshown to reduce the visibility of age spots without reducing their size or number, and can be useful in the tretment of melasmaex: alpha hydroxy acids, linoleic acid13Traditional Chinese MedicineCinnamic AcidA naturally occuring aromatic fatty acid of low toxicity, has a long history of human exposure.the cinnamic acid was found to induce cells differentiation as evidenced by morphological changes and increased melanin production in melanoma cellsSophocarpidineSophocarpidine function as an uncompetitive inhibitor, compared to aloin and cinnamic acid, which are mixed-typed inhibitorSophocarpidine, aloin, and cinnamic acid, can not only bind to the enzyme, but also to the enzyme-subtrate complex as well14HydroquinoneHydroquinone inhibits the conversion of dopa to melanin by inhibiting the tyrosinase enzyme.Inhibition DNA and RNA synthesis, degradation of melanosomes, and destruction of melanocytes.Concentration 2%-10%Side effects : allergic contact dermatitis, irritant contact dermatitis, and post-inflammatory hyperpigmentation and nail discolorationThey are supposed to either lighten skin (individuals who wish to change or modify their skin color) or depigment skin (treatment for abnormal-hyperpigmentation skin such as melasma, freckles, and senile lentigines).15Kojic AcidA fungal metabolic product, is incresingly being used as a skin-lightening agent in skincare products marketed in Japan since 1988The mode of action of kojic acid is to suppres free tyrosinase, mainly attributable to chelation of its copper.Kaand its derivate have better inhibitory effect on tyrosinase than any other skin whitening agentIt has been used alone in concentration 2-4% and it has also been combined with HQ 2% in an AHA gel base16Ascorbic AcidInterferes with different steps of melanization, by interacting with copper icons at the tyrosinase active site and reducing dopaquinone and DHICA oxidation. Melanin can be changed from jet black to light tan by the reduction of oxidized melaninQuickly oxidised and decomposes in aqueous solution and is thus not generally useful as a depigmenting agentMagnesium-L-ascorby-2-phosphate (VC-PMG) is a vitamin C derivative that is stable in water, especially in neutral or alkaline solution containing boric acid or it salt17NiacinamideNiacinamide has no effect on tyrosinase activity, melanin synthesis, or cell number in melanocyte monoculture system, and no effect on the proliferation of keratinocytes.Niacinamide downregulated the amount of melanosomes transferred from melanocytes to surrounding keratinocytes in a coculture system by approximately 3568%.a niacinamide moisturizer was effective in reducing hyperpigmentation and in increasing lightness of basal skin color compared with control moisturizer.The efficacy of topical niacinamide for decreasing facial hyperpigmentation and lightening skin color in vehicle-controlled protocols was evaluated.Niacinamide or nicotinamide is a biologically active form of niacin (vitamin B3)18Alpha Hydroxy AcidIn low concentrations, AHAs decreased corneocyte cohesion, leading to sloughing of dead cells and stimulation of new cell growth in the basal layer. In higher concentrations, they cause epidermilysis.AHAs have been reported to be effective in treating pigmentary lesions such as melasma, solar lentigines, and post-inflammatory hyperpigmentation.The mechanism of this effect might be due to epidermal remodeling and accelerated desquamation, which would result in quick pigment dispersion. GA and LA might work on pigmentary lesions not only by accelerating the turnover of the epidermis but also by directly inhibiting melanin formation by inhibiting tyrosinase in melanocytes.Niacinamide or nicotinamide is a biologically active form of niacin (vitamin B3)19Thank You