SKIN WHITENING AGENT By: Hala shindi Maysam manasrah Instructor: Yassen Qwassmi What that gives skin its color: Skin color results from the synthesis and distribution of melanin in the skin , and produced by specialized cells, termed melanocytes in the epidermis layer. The melanins can be of two basic types: 1)Eumelanins, which are gives brown or black skin color. 2)Phaeomelanins, which are gives red or yellow skin color. Synthetic of melanin Melanocytes synthesize melanin within discrete organelles, termed melanosomes, which can be produced in varying sizes, numbers, and densities. The melanosomes are then passed on, in skin to keratinocytes, where the final distribution patterns of the pigment are determined. This distribution plays an important role in determining color. Skin color is due to the type of pigments called melanin granules cells called Almilanossit called melanin production process on behalf of melanogenesis. •This is the production of melanin in the inner layers of the skin layer and in the dermis layer and then paid to the surface layer of skin to skin to gain its distinctive color • The occurrence or the beginning of melanin synthesis due to the presence of amino acid called tyrosine and tyrosine synthesis begins in the liver through the conversion of phenylalanine to tyrosine phenylalanine by the enzyme phenylalanine hydroxylase,. What causes darkening of the skin The main physiological stimulus of melanogenesis is the UV radiation of solar light, which can act directly on melanocytes or indirectly through the release of keratinocyte-derived factors stimulating hormone). Increased production and accumulation of melanins characterize number of skin diseases, which include hyperpigmentation such as melanoma, post-inflammatory melanoderma, solar lentigo, etc. Several modalities of treatment for these problems are available including chemical agents or physical therapies. Skin whitening agent: Skin whitening products are commercially available for cosmetic purposes in order to obtain a lighter skin appearance.. Whitening agents act at various levels of melanin production in the skin. Many of them are known as competitive inhibitors of tyrosinase, the key enzyme in melanogenesis. Others inhibit the maturation of this enzyme or the transport of pigment granules (melanosomes) from melanocytes to surrounding keratinocytes. skin whitening agents work by depigmenting activity : Depigmentation can be achieved by: (i) regulating the transcription and activity of tyrosinase. (ii) regulating the uptake and distribution of melanosomes in recipient keratinocytes. (iii) interference with melanosomes maturation and transfer. However, as a result of the key role played by tyrosinase in the melanin biosynthesis, most whitening agents acts specially to reduce the function of enzyme by mean of several mechanisms Therefore, tyrosinase inhibitors have become increasingly important in the cosmetic and medicinal products used in the prevention of hyperpigmentaion and skin whitening NATURAL WHITENING PRODUCTS BLOCKING TYROSINASE I. Phenols: (I) Arbutin and Derivatives isolated from the fresh fruit of California buckeye the inhibit the oxidation of L-DOPA catalyzed by mushroom tyrosinase and was effective in the topical treatment of various cutaneous hyperpigmentations characterized by hyperactive melanocyte function. Structurally related to hydroquinone, arbutin inhibited tyrosinase activity by interacting at the active site with copper (II) Kojic Acid and Derivatives produced by several species of fungi, especially Aspergillus oryzae, which has the Japanese common name koji. How it work ? Kojic acid was a tyrosinase inhibitor derived from various fungal species such as Aspergillus and Penicillium. Its function was chelating copper at the active site of the tyrosinase and scavenging free radicals (III) Gentisic Acid and Derivatives found in gentian roots good inhibitor of melanogenesis. Its alkyl esters were investigated as tyrosinase inhibitors in vitro and in cell cultures. Methyl gentisate appeared to be more efficient than the free acid form as well as other well-known hypopigmenting Agents. II. Polyphenols Polyphenols are a group of chemical compounds that are widely distributed in nature and are also known as tannins because they are responsible for the colors of many flowers. (I) Flavonoids Abundantly present in acid fruits known as "citrus" - oranges, lemons, tangerines and grapefruit Flavonoids inhibit enzymes due to abilities to chelate copper at their site .A recent the active fluorescence quenching study demonstrated that dihydroxy substitutions in both rings of flavonoids are crucial for tyrosinase inhibitory activity (II) Aloesin Aloesin was a glycosylated chromone isolated from the aloe plant Its structure was rather similar to flavonols. It modulated melanogenesis via competitive inhibition of tyrosinase . Combined treatment of aloesin and arbutin seemed to show synergistic effects by respectively non-competitive and competitive tyrosinase inhibition ) . (III) Procyanidins Procyanidins, polymers of catechins found in tea and fruits such as apples and grapes Procyanidins had been recently introduced as inhibitors of melanogenesis. Procyanidinrich extract would reduce DOPA-postive melanocytes and 8-hydroxy-2′-deoxyguanosine positive melanin containing cells, and this effect may related to inhibition of tyrosinase (IV) Ellagic Acid Ellagic acids (EA) was a polyphenol found in berries, green tea and pomegranate with strong antioxidative properties and tyrosinase inhibition . The skin lightening effects of EA may due to chelating copper at the active site of tyrosinase to reduce its activity and inhibition of proliferation of melanocytes and melanin synthesis . (68) ( 67) (68) Risks and detriments • Some people are developing skin lightening cream on the entire body in order to change the color of their skin completely. This action involves high risk, as a active ingredients in some skin lightening creams is mercury, and this has led practically to the incidence of mercury poisoning. Mercury is a toxic elements, which can cause psychological problems and serious neurological damage in addition to the kidney. Can pregnant women who use skin lightening creams containing mercury (Mercury) that Ikmn passing mercury to their unborn. •also hydroquinone which are used to relieve the activity of cells when Irritation of the pigment melanin in the body, they greatly harm a pregnant woman ,and is considered to be highly cytotoxic to melanocytes , It can be irritating and causes redness and burning , impaired wound healing • And cortisone Cortisone material is considered hazardous material and cause when used for skin lightening in skin atrophy and increased hair growth In some areas of the body. Side effects of skin whitening application: • Dermatitis with severe drying, cracking of the skin and itching • Melasma and hyperpigmentation of the skin • Mercury poisoning • Fetal toxicity in pregnant women • Cushing’s syndrome • Liver failure • Skin cancer . The hypopigmentation (lack of skin pigment) leaves the skin prone to UV damage by sunlight. This can predispose to skin cancers like a melanoma. Therefore, you should use sunscreens T h a n k y o u f o r l i s t e n i n g y o u r