Skin lightening refers to the ability of a product to reduce hyper-pigmented areas or spots on the skin. These products, also referred to as skin-whiteners, brighteners, or bleach creams, try to even and lessen skin coloration due to the formation of excessive melanin.
The Biology of Skin Pigmentation
The skin pigmentation process is complex. It’s believed there are at least 14 primary mechanisms involved in the formation of skin color, as well as 3 secondary ones. Skin color originates in the epidermis, where the pigment-producing cells, melanocytes, are located.
Upon UV exposure, these cells produce pigment, called melanin. This process is referred to as melanogenesis (see figure below-right) and is controlled by the copper-containing enzyme tyrosinase. Tyrosinase is located in vesicles called melanosomes which are inside melanocytes.
Two types of pigments are synthesized in melanosomes: eumelanin and pheomelanin. Eumelanin is a dark brown-black insoluble polymer, and pheomelanin is a light red-yellow sulphur containing soluble polymer.
Most skin-lighteners (EU) target tyrosinase inhibition as the main mechanism. New actives have been developed that claim to interfere with the transfer of melanosomes to keratinocytes. Another efficient mechanism would be to block the up-regulation of tyrosinase and block the stimulation of melanocyte dendricity. This could be achieved by interfering with the binding of keratinocyte mediators to their melanocyte receptors or by inhibiting the production of these mediators.
Skin-lightening strategies include utilizing combinations of materials that work by different mechanisms. All skin-lightening formulations should contain a chelating agent (EU), an antioxidant (EU), and a skin-soothing agent (EU).
- Tyrosinase synthesis and activity.
- Phenylalanine hydroxylase (PAH).
- Tyrosinase hydroxylase isoenzyme 1 (TH-I).
- Dopa oxidase
- Tyrosinase-related proteins (TRP-1,2) similar to tyrosinase.
- Antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase and thioredoxin reductase.
- Protease-activated receptor 2 (PAR-2) inhibition may have an impact on melanosome transfer.
- Binding to the peroxisome proliferator activated receptor-gamma (PPAR-gamma) and thereby inhibiting the mRNA and protein levels.
- Inhibit melanocyte dendricity.
- Inhibit melanin stimulating hormone (MSH).
- Melanosome transfer inhibitors.
- Reduce skin irritation, which is known to stimulate hyperpigmentation.
- Inhibit microphthalmia-associated transcription factor gene (MITF) expression. MITF plays a central role in melanin synthesis, as well as melanosome biogenesis and transport.
- Increase cell turnover and desquamation.
- Chelating agents – copper (EU) is essential for tyrosinase activity. Utilize antioxidants. UV irradiation can produce reactive oxygen species (ROS) in the skin that may induce melano-genesis by activating tyrosinase.
- Utilize cosmetic anti-inflammatory agents (EU).
- Serine protease inhibitors may also inhibit Melanosome transfer.
Licorice PT-40 by Barnet Products (Glycyrrtiiza Glabra (Licorice Root Extract))
Glabrene, glabridin, and isoliquiritigenin in licorice extract can inhibit both mono/diphenolase and tyrosinase activities. PT-40 contains 40% glabridin, which is probably one of the most potent tyrosinase inhibitors currently on the market (.2 ppm, 44% melanin inhibition).
Emblica™ by EMD (phyllanthus emblica (fruit) extract)
Has antioxidant activity, chelating properties, and inhibits MMP-1 and MMP-3. 2% emblica was shown to be as effective as 2% hydroquinone in in the skin of Hispanic volunteers.
Synovea® HR by Sytheon (hexyl resorcinol)
At .5%, it has been clinically shown to be as effective as 2% hydroquinone. You may also be able to reduce the amount of preservative you need due to its strong antimicrobial activity.
EU: Synovea® HR | Sytheon
4% N-Acetyl Glucosamine and 2% Niacinamide Complex
Topical application of a 4% n-acetyl glucosamine and 2% niacinamide complex produced visible improvement in pigmentation after 8 weeks (P&G study).
GenoWhite™ by Corum
A new skin lightning peptide claimed to inhibit melanosome formation by interfering with the key enzymes (TRP-1: -41%, TRP-2: -75%, tyrosinase: -41%) and a key regulator (MITF: -37%) in the melanogenesis pathway. Excellent whitening efficacy was demonstrated ex-vivo (existing melanin level: -30%) in 9 days and spot-brightening (mean luminance: +1.71%) after 14 days.
A350 by Miwon (myristoyl tripeptide-31)
An anti-aging / skin-lightening active that has a high affinity for the alpha MSH receptor and can inhibit tyrosinase activity. A formulation containing 2% A350 (4 ppm active) was shown to reduce wrinkle numbers by 30%, wrinkle area by 35%, and wrinkle length by 33% after 12 weeks of treatment. Skin color was also reduced by 1.8 L value units.
Oligopeptide-68 by Uniplex Innovations
A novel skin-lightening active that inhibits tyrosinase, MITF, TRP-1, and TRP-2. MITF is a critical factor in melanogenesis.
WhitenCFL® by Jiangsu High Hope International Group Sunshine Chemical Corporation (Deoxyarbutin)
3% had similar skin lightening activity as 4% hydroquinone in an SCC-published clinical study.
EU: WhitenCFL® | Jiangsu High Hope International Group Sunshine Chemical Corporation
Several fragrance compounds may be useful in skin-lightening products. Developing a fragrance designed for skin-lightening products could be useful to increase efficacy. The following have significant tyrosinase inhibition at 100ug/ml:
J. M. Gillbro, M. J. Olsson, The melanogenesis and mechanisms of skin-lightening agents – existing and new approaches. Int. J. Cosmet. Sci. 2011, 33, 210-221.
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