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SKIN Whitening

Group VII

Skin Colour
The 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.

Skin and Melanin


Skin 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 Melanin


These 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.

Melanin
Two 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 pheomelanin

Melanin
Melanin 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.

Skin Colour
In 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.

Skin Whitening
Skin-whitening products have been widely used in the cosmetic field
and clinic therapy

Whitening agents, such as hydroquinone, kojic acid, and ascorbic acid


derivatives have shown efficacy in a variety of hyperpigmentary disorders

The 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 pigment

Depigmentation
The transcription and activity of tyrosinase, TRP-1, TRP-2, and/or
peroxidase

The uptake and distribution of melanosomes in recipient keratinocytes Melanin and melanosome degradation and turnover of pigmented
keratinocytes

Tyrosinase Inhibition
Tyrosinase is a copper enzyme, which catalysis both the hydroxylation
of monophneols to o-diphenols and the oxidation of o-diquinones to oquinones.

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 control

Ex:

hydroquinone, kojic acid, azelaic acid, paper extract mulberry, arbutin, licorice extract, ellagic acid

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. all ascorbic acid is oxidized

Product Reduction and

Therefore, that melanin cannot be formed by action of tyrosinase until


Ex:
ascorbic acid, magnesium L-ascorbyl-2-Phosphate (VC-PMG), thioctic acid, alpha tocopherol

Inhibition of Melanosomes Transfer


The 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 transfer

Inhibition of Par-2 cleavage by serine protease inhibitor, such us RWJ50353, completely avoids the UVB-induced pigmentation of epidermal analogs

Ex : niacinamides, RWJ-50353, soybean tripsin inhibitor,

Skin Turnover Acceleration


The capacity of several compounds to disperse melanin pigment
and/or accelerate epidermal turnover can result in skin lightening

Topical apllication has beenshown to reduce the visibility of age spots


without reducing their size or number, and can be useful in the tretment of melasma

ex: alpha hydroxy acids, linoleic

acid

Traditional Chinese Medicine


Cinnamic Acid A 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 cells

Sophocarpidine Sophocarpidine function as an uncompetitive inhibitor, compared to aloin


and cinnamic acid, which are mixed-typed inhibitor

Sophocarpidine, aloin, and cinnamic acid, can not only bind to the enzyme,
but also to the enzyme-subtrate complex as well

Hydroquinone
Hydroquinone 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 discoloration

Kojic Acid


A fungal metabolic product, is incresingly being used as a skinlightening agent in skincare products marketed in Japan since 1988
The 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 agent It has been used alone in concentration 2-4% and it has also been combined with HQ 2% in an AHA gel base

Ascorbic Acid
Interferes 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 melanin

Quickly oxidised and decomposes in aqueous solution and is thus not


generally useful as a depigmenting agent

Magnesium-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 salt

Niacinamide


Niacinamide 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.

Alpha Hydroxy Acid


In 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.

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