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95 Resorcinol edit main article: Resorcinol Resorcinol or m-hydroquinone is often used in skin-lightener cosmetics in countries where free hydroquinone is prohibited. Arbutin edit some of alternative lighteners are derived from natural sources of hydroquinone. These include mitracarpus scaber extract, uva ursi ( bearberry ) extract, morus bombycis ( mulberry morus alba ( white mulberry and Broussonetia papyrifera ( paper mulberry ). All of these contain arbutin (technically known as hydroquinone-β-d-glucoside which can inhibit melanin production. Pure forms of arbutin are considered more potent for affecting skin lightening. Arbutin is derived from the leaves of bearberry, cranberry, mulberry or blueberry shrubs, and also is present in most types of pears. It can have melanin -inhibiting properties. 96 Arbutin and other plant extracts are considered safe alternatives to commonly used depigmenting agents to make the skin fairer. Medical studies have shown the efficiency of arbutin for skin lightening. 97 not in citation given There are patents controlling its use for skin lightening. Arbutin actually exists in two isomers, alpha and beta. The alpha isomer offers schoonheidsspecialiste higher stability over the beta isomer and is the preferred form for skin lightening indications. Kojic acid edit kojic acid is a by-product in the fermentation process of malting rice for use in the manufacturing of sake, the japanese rice wine.
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France ) because of tibetan fears of a cancer risk. However, other European countries (e.g. Spain ) have both prescription and nonprescription formulations. 93 Some concerns about hydroquinone's safety on skin have been expressed, but the research when it comes to topical application indicates negative reactions are minor or a result of using extremely high concentrations or from other skin-lightening agents such as glucocorticoids or mercury iodine. Any perceived risk is most likely applicable for African women. 94 Hydroquinone has been shown to cause leukemia in mice and other animals. The european Union banned it from cosmetics in 2001, but it shows up in bootleg creams in the developing world. It is sold in the United States as an over-the-counter drug, but with a concentration of hydroquinone not exceeding 2 percent. Because of hydroquinone's action on the skin, it can be an irritant, particularly in higher concentrations of 4 or greater and predictably when combined with tretinoin. Some medications have been created that combine 4 hydroquinone with tretinoin and a form of cortisone. The cortisone is included as an anti-inflammatory. The negative side effect of repeated application of cortisone is countered by the positive effect of the tretinoin so that it does not cause thinning of skin and damage to collagen.
skin can tan. Using tretinoin always makes the skin more sensitive to uva and uvb rays. During melanin synthesis edit hydroquinone edit main article: Hydroquinone In medical literature, hydroquinone is considered the primary topical ingredient for inhibiting melanin production. Its components have potent antioxidant abilities. 91 Topical hydroquinone comes in 2 (available in cosmetics, often as monobenzone ) to 4 (or more) concentrations (available from a physician or by prescription alone or in combination with tretinoin.05.1. Research has shown hydroquinone and tretinoin to prevent sun- or hormone-induced melasma. 80 Hydroquinone is a strong inhibitor of melanin production, meaning that it prevents dark skin from making the substance responsible for skin color. 92 Hydroquinone does not bleach the skin but lightens it, and can only disrupt the synthesis and production of melanin hyperpigmentation. It has been banned in some european countries (e.g.
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Directly destroying existing melanin edit several species of fungi produce enzymes that reduce pigmentation by degrading melanin. 74 These enzymes often require the presence of hydrogen peroxide and sometimes the presence of Mg2 ions to work. 74 They have been proposed as a safer alternative to hydrogen peroxide for cosmetic hair depigmentation. 74 The enzyme lignin peroxidase produced by the fungus phanerochaete chrysosporium has been studied as an ingredient suitable for skin-whitening: A double-blind placebo-controlled split-face randomized study found this enzyme to be effective and superior to hydroquinone in skin whitening. 75 In a non-controlled study, this enzyme was applied to volunteers with facial melasma during 8 weeks; the treatment was found effective in reducing pigmentation in both skin affected by melasma and skin unaffected by melasma. 76 Destroying melanocytes edit some compounds are known to destroy melanocytes; this mechanism of action is often used to remove the remaining pigmentation in cases of vitiligo. 77 78 Non-pharmacological treatments edit most skin-lightening treatments, which can reduce or block some amount of melanin production, are aimed at inhibiting tyrosinase. Many treatments use a combination of topical lotions or gels containing melanin-inhibiting ingredients along with a sunscreen, and a prescription retinoid. Depending on how the skin responds to these treatments, exfoliants either in the form of topical cosmetic or chemical peels and lasers prevage may be used. New development using led systems are also showing good results.
Notes 13 Keratinocytes are continuously generated in the basal layer of the epidermis and displace older keratinocytes of the skin towards the surface. Melanosome transfer: Melanosomes along with the melanin they contain is transferred from melanocytes to keratinocytes when keratinocytes are low in the epidermis. Notes 15 Keratinocytes carry the melanosomes with them as they move towards the surface. Keratinocytes contribute to skin pigmentation holding the melanin originated in melanocytes and induce melanogenesis through chemical signals directed at melanocytes. Notes 8 The transfer of melanosomes to keratinocytes is a necessary condition for the visible pigmentation of the skin. 65 Blocking this transfer is a mechanism of action of some skin whitening agents. 40 13 skin whitening agents that block melanocyte transfer include niacinamide, heparin, 66 madecassoside, 67 soybean 68 and Saccharomyces cerevisiae (a species of yeast). 69 The protease-activated receptor 2 (PAR2) is a transmembrane and G-protein coupled receptor expressed in keratinocytes and involved in melanocyte transfer. Notes 16 notes 17 Antagonists of par2 inhibit the transfer of melanosomes and have a skin whitening affects while agonists of par2 have the opposite effect, as expected. Notes 17 The common endogenous agonists of par2 are serine proteases which irreversibly activate par2 by cleaving a part of the extracellular terminal of this receptor thereby exposing a part of it that subsequently works as a ligand tethered to the reset of the receptor. Some synthetic agonists of par2 are short peptides that imitate the aforesaid tethered ligand but do not cleave the extracellular terminal.
Notes 10 Synthetic MC1R agonists have been designed; examples include the peptides afamelanotide and melanotan. 49 Mutations of the mc1R gene correlate, and in some individuals are at least partially responsible for red hair, white skin and an increased risk for skin cancer. Notes :1175 Serotonin signaling edit melanocytes express serotonin receptors and are capable of producing serotonin. Pharmacological interference with the serotonin system of melanocytes can result in either increased or decreased melanin synthesis. Serotonin itself is a weak inhibitor of tyrosinase 60 with.11 times the potency of kojic acid. Notes 12 Nonetheless, serotonin increases synthesis of melanin when its overall effect on melanocytes (as opposed to isolated tyrosinase ) is evaluated. 61 Activation of 5-HT2B receptors with bw-723C86 inhibits melanogenesis 62 while activation of 5-HT2A receptors with the amphetamine structural analog doi promotes melanogenesis. 63 The serotonin reuptake inhibitor (SRI) 6-nitroquipazine inhibits melanogenesis in-vitro. 64 Preventing the transfer of melanosomes to keratinocytes edit see also: human skin Structure, and epidermis For an overview of the interaction between keratinocytes and melanocytes see yamaguchi, hearing (2009). 41 Keratinocytes in the skin: Within the skin, melanocytes are present in the basal layer of the epidermis ; from these melanocytes originate dendrites that reach keratinocytes. Notes 13 Keratinocytes are the most abundant cell type in the epidermis. Notes 14 In the skin, there are approximately 36 keratinocytes per melanocyte.
Skin whitening cream for black skin - lifestyleNotes 7 Various signaling pathways and genetic mutations mutations influence the expression of mitf. Notes 8 43 44 Inhibitors of melanogenesis whose mechanism of action includes reducing the genetic expression of melanogenic enzymes include caffeoylserotonin, 45 AP736, 46 pomegranate extract, 47 and betulinic acid (extracted from Vitis amurensis root). 48 The mc1R receptor and camp edit The melanocortin 1 receptor (MC1R) is a transmembrane and G-protein coupled receptor expressed in melanocytes. MC1R is an important target for the regulation of melanogenesis. Agonism (i.e.: activation) of MC1R increases the ratio of eumelanin to pheomelanin and increases the generation of melanin overall. MC1R/camp signaling pathway: notes 8 notes Activation of MC1R causes activation of adenylyl cyclase (ac which produces cyclic adenosine monophosphate (camp which activates protein kinase a (pka which activates (by protein phosphorylation ) camp response anti element-binding protein (creb which upregulates mitf (creb is a transcription. Whitening agents that interfere with the mc1R/camp signaling pathway have been reviewed by Chang (2012). 12 camp is degraded by phosphodiesterases (PDE). The pde5 inhibitors sildenafil and vardenafil, the camp-promoter ibmx and 8-cpt-cgmp (a cyclic guanosine monophosphate (cGMP) analogue) increase melanin synthesis. 52 MC1R ligands: alpha-melanocyte stimulating hormone (α-msh notes 9 beta-melanocyte stimulating hormone (β-msh) and adrenocorticotropic hormone are endogenous agonists of MC1R. 17 :1175 Agouti signaling protein (asip) appears to be the only endogenous antagonist of MC1R.
The ic50 is highly dependent on the assay conditions, making it incomparable among different assays (unless designed to be comparable). It is customary practice in studies of creme tyrosinase inhibitors to assay one or several well known inhibitors as goedkope a positive control and point of comparison. The relative activity (RA) of a compound under investigation is its activity divided by the activity of the positive control; in turn the activity of a compound is usually defined as 1/IC50. The ra is less dependent on assay conditions that the ic50 and is suitable to compare the results of different assays provided the same positive control was used. The positive control is commonly kojic acid. Upregulation of tyrosinase caused by tyrosinase inhibitors: several skin whitening agents including some which are tyrosinase inhibitors have been found to cause an increase in the expression of tyrosinase (which by itself would increase melanin synthesis). 20 12 Irreversible inhibitors of tyrosinase include: N-nonyl trans -caffeate, 21 α-na8SiW11CoO40 (a polyoxometalate 22 a structural analog of aloe emodin, 23 structural analogues of barbituric acid, structural analogues of chalcone, 27 sodium hydrogen sulfite, 28 structural analogues of coumarin, 29 structural analogues of the. 9 Inhibition of the expression or activation of tyrosinase edit see also: transcription factor, hormone, and receptor (biochemistry) Microphthalmia-associated transcription factor (mitf) is the master transcription factor that controls the expression of tyr, trp1 and trp2, mart1, pmel17 and many other important proteins involved. Notes 6 Downregulation of mitf decreases melanogenesis notes 6 and is a mechanism of action of some skin whitening agents. 12 40 As an heuristic rule, agents acting through downregulation of mitf are more likely to have side effects that selective tyrosinase inhibitors.
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L-tyrosine is also synthesized within the melanocytes from L-phenylalanine by the enzyme phenylalanine hydroxylase (PAH). 17 :1164 Melanosomes are transferred to keratinocytes (the most abundant cell type in the skin). Most of steken the melanin of skin is found in keratinocytes. Additionally, melanocytes interact with keratinocytes through chemical signaling. See preventing the transfer of melanosomes to keratinocytes. Skin whitening agents work by reducing the presence of melanin in the skin. To accomplish this, there are several possible mechanism of actions: notes 3 13 Inhibition of the activity of tyrosinase edit further information: enzyme inhibitor Many tyrosinase inhibitors have been discovered or developed. Very many inhibitors of tyrosinase are known; most are of the reversible type. Notes 4 For a review of tyrosinase inhibitors see chang (2009). 3 reviews of patents on tyrosinase inhibitors have been published. 18 19 evaluation of effectivity: notes 5 The potency (how little of a substance is needed to achieve an effect) of reversible inhibitors is usually given in terms of its IC50.
The variation of skin color among individuals is mostly because of variation of the nachtpflege content nivea of melanin in the skin. Skin with little or no melanin is almost white. Other factors influence skin color in a lesser degree, including the amount of blood in blood vessels (because of the color of blood skin thickness and content of carotenoids in skin. 14 15 Melanin in synthesized in melanosomes which are organelles produced in melanocytes. Melanocytes are cells dedicated to this function that are present in the skin, hair follicles, and other structures of the body. The synthesis of melanin (also called "melanogenesis" and "melanization involves a chain of enzyme-catalyzed chemical reactions and non-enzyme-catalyzed reactions. Notes 2 The main precursor to melanin is L-tyrosine. The first step of melanogenesis is the conversion of L-tyrosine to l-dopa ; this is the first and rate-limiting step and is catalyzed by the enzyme tyrosinase (TYR). 17 :1163 Other enzymes involved in the synthesis include tyrosinase-related protein 1 (TRP1) and tyrosinase-related protein 2 (TRP2 trp2 is also known as "dopachrome tautomerase" (DCT). L-tyrosine is taken by the melanocytes from the intercellular medium, then transported to the melanosomes.
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Skin whitening notes 1 is the huid practice of using substances, mixtures, or physical treatments to lighten skin color. Skin whitening treatments work by reducing the content of melanin of the skin. Many agents have been shown to be effective in skin whitening; some have beneficial side effects (e.g.: are antioxidants, 1 nutrients, or decrease the risk of some types of cancer some are a significant risk to health (for example, those containing mercury). Contents, specific zones of hyperpigmentation such as lentigo spots, moles and birthmarks may be depigmented to match to the surrounding skin. In cases of vitiligo, unaffected skin may be lightened to achieve a more uniform appearance. 2, discovery and design edit, melanogenesis kopen inhibitors have been discovered and developed through several methods, including: screening of synthetic chemical libraries ( high throughput screening is occasionally used screening of plant extracts, 3 computational ( in silico ) search, 4 5 found as a side. Thus, the development and discovery of melanogenesis inhibitors illustrates many of the methods used in drug design. Some of the most potent competitive reversible tyrosinase inhibitors are synthetic compounds with a potency hundreds of times that of kojic acid. Mechanisms of action edit, see also: melanocyte, melanin, enzyme inhibitor, skin color, and hair color For a review of mechanism of action of skin whitening agents, see chang (2012) 12 or Ebanks, wickett, boissy (2009). 13 Melanin is the main substance responsible for the color of the skin. Melanin is class of dark polymers generated by the body through the process of melanogenesis. Among the melanin pigmenting the skin and hair, 2 types can be distinguished based on its chemical composition and biological route of synthesis: the black/brown eumelanin and the red/yellow pheomelanin.