Skin whitening is the practice of using substances, mixtures, or physical treatments to brighten skin tone. Skin whitening treatment works by reducing the melanin content of the skin. Many agents have proven effective in whitening skin; some have beneficial side effects (eg: antioxidants, nutrients, or reduce the risk of some cancers); some significant risks to health (eg, containing mercury).
Video Skin whitening
Usage
Specific hyperpigmentation zones such as lentigo spots, moles and birthmarks may be depigmented to fit the surrounding skin. In the case of vitiligo, unaffected skin can be alleviated to get a more uniform appearance.
Maps Skin whitening
Invention and design
The melanogenesis inhibitor has been discovered and developed through several methods, including: synthetic chemical screening (high throughput screening sometimes used), plant extract filtering, computational (in silico) search, found as a side effect of previously known drugs and structural analogue exploration from previously known tyrosinase inhibitors based on knowledge (at various levels) of their activity-activity relationships. Thus, the development and discovery of a melanogenesis inhibitor illustrates many of the methods used in drug design. Some of the most powerful competitive tyrosinase inhibitors are synthetic compounds with the potential of hundreds of times kojic acid.
Action mechanism
- To review the workings of skin whitening agents, see Chang (2012) or Ebanks, Wickett, Boissy (2009).
Melanin is the main substance responsible for skin color. Melanin is a class of dark polymers produced by the body through the process of melanogenesis. Among melanin pigment skin and hair, two types can be distinguished based on their chemical composition and biological synthesis route: black/brown eumelanin and red/yellow pheomelanin . Skin color variation among individuals is mostly due to variations of melanin content in the skin. Skin with little or no melanin is almost white. Other factors affect skin color in lower levels, including the amount of blood in the blood vessels (due to blood color), skin thickness and carotenoid content in the skin.
Melanin is synthesized in melanosomes which are organelles produced in melanocytes. Melanocytes are cells dedicated to this function that exist in the skin, hair follicles, and other body structures. Melanin synthesis (also called "melanogenesis" and "melanization") involves the chemical reaction chain of the catalyst-enzyme and non-reaction-catalyzed enzymes. The main precursor for melanin is L -tyrosine. The first step of melanogenesis is the conversion of L -tyrosine to L -DOPA; this is the first step and rate limitation and is catalyzed by a tyrosinase enzyme (TYR). : 1163 Other enzymes involved in synthesis include protein 1 related tyrosinase (TRP1) and tyrosinase 2-associated proteins (TRP2); TRP2 is also known as "dopachrome tautomerase" (DCT). L -tyrosine is taken by melanocytes from intercellular media, then transported to melanosomes. L -tyrosine is also synthesized in melanocytes from L -phenylalanine by phenylalanine hydroxylase (PAH) enzyme. : 1164
Melanosomes are transferred to keratinocytes (the most abundant type of cells in the skin). Most skin melanin is found in keratinocytes. In addition, melanocytes interact with keratinocytes through chemical signaling. See Ã, § Prevent melanosomes transfer to keratinocytes.
Skin whitening agents work by reducing the presence of melanin in the skin. To achieve this, there are several possible mechanisms of action:
- Inhibition of tyrosinase activity: The catalytic action of tyrosinase is inhibited (slowed or almost stopped) by skin bleaching agents.
- Inhibition of expression or activation of tyrosinase: An antimelanogenic agent causes less resulting tyrosinase or tyrosinase not activated into its functional form.
- Rolls the product between melanin synthesis.
- Prevents the transfer of melanosomes to keratinocytes.
- Destroying existing melanin directly.
- Destroy melanocytes.
Inhibits tyrosinase activity
Many tyrosinase inhibitors have been discovered or developed. Very many known tyrosinase inhibitors; most are of the reversible type. For a review of tyrosinase inhibitors see Chang (2009). Patent reviews on tyrosinase inhibitors have been published.
Evaluation of effectiveness: The potential (how few substances are required to achieve the effect) of reversible inhibitors is usually given in the case of IC 50 . IC 50 is highly dependent on test conditions, so it can not be compared with different tests (unless designed to be comparable). It is a custom practice in the study of tyrosinase inhibitors to test one or several famous inhibitors as a positive control and point of comparison. The relative activity (RA) of the compound under study is the activity divided by the positive control activity; in turn the activity of a compound is usually defined as 1/IC 50 . RA is less dependent on test conditions that IC 50 and is suitable for comparing different test results by using the same positive control. The positive control is generally kojic acid.
Increased tyrosinase caused by tyrosinase inhibitors: Some skin whitening agents including some of the tyrosinase inhibitors have been found to cause increased increase in tyrosinase expression (which in itself will increase melanin synthesis).
Unchangeable tyrosinase inhibitors include: N-nonyl trans -kaffeat ,? (A polyoxometalate), a structural analogue of aloe emodin, a structural analogue of barbituric acid, a structural analog of chalcone, sodium hydrogen sulfite, structural analogue of coumarin, structural analog of the following two compounds: benzene-1, 2-diamine and 2-aminophenol, and 2,3-dihydroxybenzoic acid itself, tetrahydrofolic acid, pyrimidine and rhodanin analogues, tetrahydropterin, trieno cardol (triena analog of cardol extracted from cashew nut), N - (3,5-dihydroxybenzoyl) -6-hydroxytryptamine, aminoethylisothiourea, 8-hydroxynaringenine, NADH, 8-hydroxydaididein and captopril.
Inhibition of expression or activation of tyrosinase
Microphthalmia-associated transcription factor (MITF) is a master transcription factor that controls the expression of TYR, TRP1 and TRP2, MART1, PMEL17 and many other important proteins involved in melanocyte function. Downregulation of MITF decreases melanogenesis and is the working mechanism of some skin whitening agents. As a heuristic rule, agents acting through MITF downregulation are more likely to have selective side effects of tyrosinase inhibitors. Signal pathways and mutation of genetic mutations affect MITF expression.
Melanogenesis inhibitors whose mechanism of action include reducing the genetic expression of melanogenic enzymes include caffeoylserotonin, AP736, pomegranate extract, and betulinic acid (extracted from Vitis amurensis root).
MC1R and cAMP receptors
The melanocortin 1 receptor (MC1R) is a paired receptor and G-protein expressed in melanocytes. MC1R is an important target for melanogenesis regulation. Agonism (ie: activation) of MC1R increases the ratio of eumelanin to pheomelanin and increases overall melanin generation.
MC1R/cAMP signaling pathway: Activation of MC1R leads to activation of adenylyl cyclase (AC), which produces cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA), which activates (by phosphorylation of proteins) cAMP response element-binding protein (CREB), which regulates MITF regulation (CREB is a MITF transcription factor). Bleach agents that interfere with the MC1R/cAMP signal path have been reviewed by Chang (2012).
cAMP is degraded by phosphodiesterase (PDE). PDE5 sildenafil and vardenafil, cAMP-promoter of IBMX and 8-CPT-cGMP (an analog cyclic guanosine monophosphate (cGMP)) increase melanin synthesis.
MC1R ligand: alpha-melanocyte stimulating hormone (? -MSH), beta-melanocyte stimulating hormone (? -MSH) and adrenocorticotropic hormone are endogenous agonists of MC1R. : 1175 Agouti signaling protein (ASIP) appears to be the only endogenous MC1R antagonist. MC1R synthetic agonists have been designed; examples include afamelanotide peptides and melanotan II.
Mutations of the MC1R gene are correlated, and in some individuals are at least partly responsible for red hair, white skin and an increased risk for skin cancer. : 1175
Serotonin signaling
Melanocytes express serotonin receptors and are capable of producing serotonin. Pharmacological interference with the melanocyte serotonin system can result in increased or decreased melanin synthesis. Serotonin itself is a weak inhibitor of tyrosinase with 0.11 times the potential of kojic acid. Nonetheless, serotonin increases melanin synthesis when the overall effect on melanocytes (compared with isolated tyrosinase ) is evaluated. Activation of 5-HT receptors 2B with BW-723C86 inhibits melanogenesis while activation of 5-HT receptor 2A with structural amphetamine structural DOI promotes melanogenesis. The serotonin reuptake inhibitor (SRI) 6-nitroquipazine inhibits in-vitro melanogenesis.
Prevents the transfer of melanosomes to keratinocytes
- For an overview of interactions between keratinocytes and melanocytes see Yamaguchi, Hearing (2009).
Keratinocytes in the skin: Inside the skin, melanocytes are present in the basal layer of the epidermis; of these melanocytes come dendrites that reach keratinocytes. Keratinocytes are the most abundant type of cells in the epidermis. In the skin, there are about 36 keratinocytes per melanocyte. Keratinocytes continue to be produced in the basal layer of the epidermis and replace the older skin keratinocytes to the surface.
Melanosome transfer: Melanosomes along with the melanin they contain are transferred from melanocytes to keratinocytes when keratinocytes are low in the epidermis. Keratinocytes carry melanosomes with them as they move to the surface. Keratinocytes contribute to the skin pigmentation that retains melanin derived from melanocytes and induces melanogenesis through chemical signals directed at melanocytes. The transfer of melanosomes to keratinocytes is a necessary condition for visible skin pigmentation. Blocking this transfer is the working mechanism of some skin whitening agents. Skin whitening agents that block melanocyte transfers include niacinamide, heparin, madecassoside, soybeans and Saccharomyces cerevisiae (yeast).
The protease-activated receptor 2 (PAR2) is a paired receptor and G-protein contained in keratinocytes and involved in the transfer of melanocytes. The PAR2 antagonist inhibits the transfer of melanosomes and has skin whitening effect while the PAR2 agonist has the opposite effect, as expected. The common endogenous agonist of PAR2 is a serine protease that irreversibly activates PAR2 by dividing the portion of the extracellular terminal of this receptor thus exposing a portion of it which then acts as a tethered ligand to a receptor reset at molecular scale. Some synthetic agonists PAR2 are short peptides that mimic ligands that are tethered on top but do not divide the extracellular terminals.
Destroy directly the existing melanin
Some fungal species produce enzymes that reduce pigmentation by decreasing melanin. These enzymes often require the presence of hydrogen peroxide and sometimes the presence of Mg 2 ion to work. They have been proposed as a safer alternative to hydrogen peroxide for cosmetic hair depigmentation.
The lignin peroxidase enzyme produced by phanerochaete chrysosporium fungus has been studied as a suitable ingredient for skin whitening: A randomized double-blind placebo-controlled split-face study found this enzyme to be effective and superior to hydroquinone in skin whitening. In an uncontrolled study, this enzyme was applied to volunteers with facial melas for 8 weeks; treatment is found to be effective in reducing pigmentation in both skin affected by melasma and the skin is not affected by melasma.
Destroying melanocytes
Some compounds are known to damage melanocytes; this mechanism of action is often used to eliminate the remaining pigmentation in the case of vitiligo.
Non-pharmacological treatments
Most skin-lightening treatments, which can reduce or block some melanin production, are intended to inhibit tyrosinase. Many treatments use a combination of topical lotions or gels containing melanin inhibitors together with sunscreens, and prescribed retinoids. Depending on how the skin responds to this treatment, exfoliants-whether in the form of topical cosmetics or chemical peels-and lasers can be used. The new development using LED system also shows good results.
Bleach agent
Pre-melanin synthesis
Tretinoin
Studies have shown that the use of tretinoin (also known as all-trans retinoic acid) can only be effective in treating skin discoloration. Tretinoin users should avoid sunlight, because the skin can be brown. Using tretinoin always makes the skin more sensitive to UVA and UVB rays.
During melanin synthesis
Hydroquinone
In medical literature, hydroquinone is considered a major topical ingredient to inhibit melanin production. Its components have a strong antioxidant capability. Topical hydroquinone comes in 2% (available in cosmetics, often as monobenzone) to 4% (or more) concentrations (available from the doctor or by prescription), alone or in combination with tretinoin 0.05% to 0.1%. Research has shown hydroquinone and tretinoin to prevent melasma caused by sun or hormones.
Hydroquinone is a strong inhibitor of melanin production, which means it prevents dark skin from making substances responsible for skin tone. Hydroquinone does not whiten the skin but enlightens it, and can only interfere with the synthesis and production of melanin hyperpigmentation. It has been banned in some European countries (eg France) for fear of cancer risk. However, other European countries (eg Spain) have both prescription and nonprescription formulations.
Some concern about the safety of hydroquinone on the skin has been disclosed, but research when it comes to topical applications shows a small negative reaction or due to the use of very high concentrations or from other skin lightening agents such as glucocorticoids or iodine mercury. Any perceived risk is likely to apply to African women. Hydroquinone has been shown to cause leukemia in mice and other animals. The European Union banned it from cosmetics in 2001, but appeared in pirated creams in developing countries. It is sold in the United States as over-the-counter drugs, but with hydroquinone concentrations not exceeding 2 percent.
Due to the hydroquinone action on the skin, it can be an irritant, especially in higher concentrations of 4% or greater and can be suspected when combined with tretinoin. Several drugs have been made that incorporate 4% hydroquinone with tretinoin and cortisone forms. Cortisone is included as an anti-inflammatory. Negative side effects of recurrent cortisone applications are countered by the positive effects of tretinoin so as not to cause skin thinning and collagen damage.
Resorcinol
Resorcinol or m-hydroquinone is often used in skin-lightener cosmetics in countries where free hydroquinone is prohibited.
Arbutin
Some alternative lighteners come from natural sources of hydroquinone. These include extracts of Mitracarpus scaber, extracts of beans, Morus bombycis (mulberry), Morus alba (< white mulberry), and Broussonetia papyrifera (mulberry paper). All of these contain arbutin (technically known as hydroquinone -? - D -glucoside), which can inhibit melanin production. A pure arbutin form is thought to be stronger to affect skin lightening.
Arbutin comes from bearberry leaves, cranberries, mulberry or blueberry bushes, and is also present in most types of pears. It can have melanin inhibitory properties. Arbutin and other plant extracts are considered as a safe alternative to depigmentation agents commonly used to make skin brighter. Medical research has demonstrated the efficiency of arbutin for skin lightening. There is a patent that controls its use for skin lightening. Arbutin actually exists in two isomers, alpha and beta. The alpha isomer offers higher stability to beta isomers and is the preferred form for skin light indication.
Kojic Acid
Kojic acid is a by-product in the fermentation process of malting rice for use in the manufacture of sake, Japanese rice wine. Some studies have shown that kojic acid is effective in inhibiting melanin production. However, kojic acid is an unstable material in cosmetic formulations. After exposure to air or sunlight, he can turn brown and lose its efficacy. Many cosmetic companies use kojic dipalmitate as an alternative because it is more stable in the formulation. However, no studies have shown kojic dipalmitate to be as effective as kojic acid, although it is a good antioxidant. Furthermore, several controversial studies have suggested that kojic acid may have carcinogenic properties in large doses. Other further studies show that kojic acid is not carcinogenic, but it can cause allergic contact dermatitis and skin irritation.
Azelaic acid
Azelaic acid is a component of grains, such as wheat, rye, and barley. This is applied topically in cream formulations at concentrations of 10-20%. Azelaic acid is used to treat acne, but there are also studies that show it to be effective for skin discoloration. Other studies have also shown that azelaic acid may be an option to inhibit melanin production.
Vitamin C
Vitamin C and its various forms (ascorbic acid, magnesium ascorbyl phosphate, etc.) are regarded as effective antioxidants for the skin and help brighten the skin. One study found that this increased levels of glutathione in the body. Another study found that brown guinea pigs that were given vitamin C, vitamin E and L-cysteine, simultaneously, caused brighter skin.
Glutathione
Glutathione is a tripeptide molecule found in the body of a mammal. It is an antioxidant that plays an important role in preventing oxidative damage to the skin. In addition to its well-known biological function, glutathione is also associated with the ability to whiten skin. While skin whitening reduces melanin that serves as a natural protection from UV exposure, the antioxidant properties of glutathione also protect the skin from UV radiation.
A double-blind placebo-controlled study found glutathione to be effective as a skin whitening agent and in reducing black spots; 500 mg dosage regimen per day (divided into 2 equal doses per day) for 2 - 4 weeks. In contrast, a study examining the effects of glutathione and related compounds in-vitro found that glutathione monoethyl ester but not glutathione had a depigmentation effect. Reviews on the use of glutathione for skin lightening are published in 2016.
Glutathione is an ingredient in some cosmetic preparations. Glutathione for skin whitening is available in creams, soaps, lotions, nasal sprays and syringes. Glutathione applied to the skin in the form of lotion is not efficiently absorbed by the skin cells as thiol groups undergo rapid formation of disulfide. When taken orally, glutathione is hydrolyzed by enzymes in the gastrointestinal tract thus reducing bioavailability. Glutathione levels increase in small quantities temporarily when large oral doses are administered. Consequently, the effectiveness of glutathione given externally is slowed by its inability to efficiently cross cell membranes and rapid degradation by enzymes in the gastrointestinal tract. In contrast, intravenous glutathione gives very high doses directly to the systemic circulation and is the preferred mode of administration of glutathione. However, this method of antioxidant administration can flood the cells with glutathione which can cause reductive stress. This can expose people to potential health risks associated with long-term use of high-dose glutathione. Of all the glutathione products, glutathione tablets remain the most effective type.
Glutathione can be combined with many other agents such as vitamin C to increase its absorption, N-acetyl cysteine ​​to increase its levels, and other antioxidants such as vitamin E. Some oral glutathione intake can have harmful effects when combined with skin whitening agents others such as hydroquinone which are carcinogenic and monobenzone elements that cause irreversible depigmentation.
Post-melanin synthesis
Alpha hydroxy acids
Alpha hydroxy acids (AHAs) - mainly in the form of lactic acid and glycolic acid - are the most researched forms of AHAs because they have molecular sizes that allow effective penetration into the upper layers of the skin. It is generally assumed that in and of themselves AHAs in concentrations of 4% to 15% are ineffective to inhibit melanin production and will not alleviate skin discoloration in this way. It is believed that the benefit is to help the rate of cell turnover and remove unhealthy or abnormal superficial skin cells (peels) in which hyperpigmentation cells can accumulate. However, other studies have shown that lactic acid and glycolate can inhibit melanin production that is separate from their actions as skin peels.
Peeling of alpha hydroxy acid (using a concentration of 50% or greater) can eliminate skin discoloration. Only qualified doctors should do this type of skin.
Niacinamide
Niacinamide is claimed to be a much safer alternative when applied topically for skin bleaching or genitalia. According to research by Procter & amp; Gamble, the cosmetics company, niacinamide has no adverse side effects. It also promotes the reduction of acne, improves skin moisture, and reduces fine wrinkles.
Other/not grouped
Depositors
Most commonly, skin depigmentation is associated with people born with vitiligo, which produces various areas of light and dark skin. These people, if they decide to use the process of enlightenment to flatten their skin color, can use a topical cream containing monobenzone organic compounds to reduce the remaining pigments. Monobenzone can cause melanocyte damage and permanent depigmentation. An alternative method of enlightenment is to use chemical mequinol over a long period of time. Increasingly, people who do not suffer from vitiligo experiments with lower concentrations of monobenzone cream in hopes of brightening their skin tone evenly. However, monobenzone is not recommended for skin conditions other than vitiligo.
Mercury
Many skin whiters contain toxic mercury, such as mercury (II) chloride or ammonia mercury as the active ingredient. However, mercury has been banned in most countries for use in skin whitening (1976 in Europe, 1990 in the US) because it accumulates on the skin and can have opposite results in the long run. Until the end of January 2016, the FDA issued a warning not to use a special bleach brand - Vesisilk's "Crema Piel De Seda" ("Silky Skin Cream"), sold in the United States for mercury.
Tranexamic acid
Tranexamic acid is sometimes used in skin whitening as a topical agent, injected into the lesions, and is drunk, both alone and in addition to laser therapy; by 2017 its security seems reasonable but its efficacy for this purpose is uncertain because there is no large-scale randomized controlled study or long-term follow-up study.
More
Another option with some amount of research on their potential skin lightening ability is licorice extract (especially glabridin).
There is also a small number of studies showing oral supplements of pomegranate extract, ellagic acid, vitamin E, and ferulic acid can inhibit melanin production.
Laser Treatment
Both ablative and nonlative lasers can have a profound effect on melasma. However, the results are not always consistent, and problems have been reported (such as hypo or hyperpigmentation). Such laser treatments are more likely to produce problems for those with darker skin tones.
Cryosurgery
Another alternative to laser treatment is cryosurgery using liquid nitrogen. The destruction of controlled skin cells causes the skin to regenerate itself naturally. Excess melanin surfaces and peels off within a few days. This is especially useful in sensitive areas such as genitalia where laser treatments can leave scars. The efficacy of treatment depends on the depth of the pigment.
Adverse effects
There is evidence to suggest that some skin whitening products use active ingredients (such as mercury chloride) and hydroquinone which can be harmful. Hydroquinone is not available without a prescription in Europe. This is only available when prescribed by a medical doctor (eg GP). This also happens in many other countries, where hydroquinone can only be prescribed by doctors for certain skin conditions.
Common skin lightening cream tests available in Nigeria show that they cause mutations in bacteria and may be carcinogenic. A study examining skin lightening cream in Mexico found high concentrations of mercury in some of them.
Society and culture
In India, sales of skin lightening cream in 2012 reached about 258 tons and in 2013 sales of about $ 300 million. In 2013, the global skin lighteners market is projected to reach US $ 19.8 billion in 2018 based on sales growth especially in Africa, India-Asia and Middle East.
See also
- Procedure
- Anal bleaching
- Teeth whitening
- Depigmentation
- Taxifolin
- Face
- Sun tanning
- Xeesal
- Illness
- Vitiligo
- Albinism
- Hypopigmentation
- Hyperpigmentation
- Culture
- Whites
- Colors
- Shadism
- Venetian CeruseÃ, - white tin-based cosmetics worn by Elizabeth I of England
- Racial bleaching
- White in Japanese culture
- Colonial mentality
Note
Italics are preserved every time they appear in quotes. The text between brackets is an additional note that is not in the source.
References
Source of the article : Wikipedia
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