Wednesday, May 7, 2008

Research on skin lightening


Skin lightening

skin color is related to the number and distribution of Melanosomes,formed in and secreted by Melanocytes which are cells contain Melanin and located at the deepest layer of epidermis(Stratum Germinativum)or basal cell layer,it release melanin and absorb UV so it protects deeper tissues.

Melanin:the unique product of melanocytes which responsible for coloring skin and absorb the ultraviolet and visible spectra.

Tyrosinase:melanosomes bear a copper containing enzyme,tyrosinase,which is the rate limiting enzyme that catalyze the oxidation of tyrosine to indole 5,6 quinone and control the synthesis of melanin in epidermal melanocytes.

Melanin Biosynthesis: Tyrosine........Dopa.........Dopaquinone........Leucodopachrome......Dopachrome........5,6-Dihydroxyindole.......5,6-Indolequinone......Melanin.The skin pigmentation is the result of a complex process which occur in 4 steps:1-UV rays and biological mediators trigger the pigmentation process by stimulating the melanin producing function of the melanocytes.2-melanin is produced by the melanocytes under the effect of tyrosinase.3-the produced melanin is transferred into the upper layer of the epidermis.4-melanin migrates to the surface of the skin through the process of cell renewal.


when the production of melanin is deregulated and excessive,it is no longer distributed evenly on the skin clusters in localized areas in a disorderly fashion,forming unattractive brown spots.The sun is the primary cause of pigment spots.too much sun can cause the appearance of small round,flat solar freckles,which when they appear with age,are called age effect,the risk of hyperpigmentation increases with the aging of cells and generally appears on the areas most exposed to the sun (face, neck,hands,etc).Liver spots are blemishes on the skin associated with ageing and exposure to ultra-violet radiation from the sun. They are also known as age spots, lentigos, or senile/solar lentigines. In spite of their name, liver spots are not related to the liver.A HORMONAL CHANGE can also cause the appearance of brown patches on the face called melasma or chloasma in the case of pregnancy.and finally,some spots are reactions to the application of photo-toxic products(perfumes,plants,etc)or to certain medications.

Drugs used in skin lightening:


HQ causes reversible inhibition of cellular metabolism by affecting both DNA and RNA synthesis. The cytotoxic effects of HQ are not limited to melanocytes, but the dose required to inhibit cellular metabolism is much higher for nonmelanotic cells than for melanocytes. Thus, HQ can be considered a potent melanocyte cytotoxic agent with relatively high melanocyte-specific cytotoxicity. HQ is also a poor substrate of tyrosinase, thereby competing for tyrosine oxidation in active melanocytes. Contact dermatitis occurs in a small number of patients and responds promptly to topical steroids. An uncommon, yet important, adverse effect of HQ is exogenous ochronosis. This disorder is characterized by progressive sooty darkening of the skin area exposed to HQ. Histologically, degeneration of collagen and elastic fibers occurs. This degeneration is followed by the appearance of characteristic ochronotic deposits consisting of crescent-shaped, ochre-colored fibers in the dermis.hydroquinone may act as a carcinogen as it has a potential mutagenic properties because it is a metabolite from benzene.Some studies also report abnormal function of the adrenal glands and high levels of mercury in people who have used hydroquinone-containing cosmetics. Tretinoin has been used to enhance the efficacy of HQ.

2-Monobenzyl ether of HQ

Unlike HQ, MBEH almost always causes nearly irreversible depigmentation of the skin.In dermatology, MBEH should only be used to eliminate residual areas of normally pigmented skin in patients with refractory and generalized vitiligo. The suggested mechanism of depigmentation of MBEH is selective melanocytic destruction through free-radical formation and competitive inhibition of the tyrosinase enzyme system.

3-Azelaic acid

A naturally occurring, saturated dicarboxylic acid originally isolated from Pityrosporum ovale, azelaic acid is a rather weak competitive inhibitor of tyrosinase in vitro. In addition, azelaic acid has an antiproliferative and cytotoxic effect on melanocytes. The latter effect occurs because of a rather potent inhibition of thioredoxin reductase, an enzyme involved in mitochondrial oxidoreductase activation and DNA synthesis. Although azelaic acid was initially prescribed for the treatment of acne, it has been successfully used in the treatment of lentigines, rosacea, and postinflammatory hyperpigmentation. It is prescribed topically.

as a 20% cream and has been combined with glycolic acid (15% and 20%). Its efficacy has been compared with HQ 4% in the treatment of facial hyperpigmentation in dark-skinned patients. The combination formula reportedly was as effective as HQ 4% cream, although with a slightly higher rate of local irritation.

4-Kojic acid (5-hydroxy-4-pyran-4-one-2-methyl)

A fungal metabolic product, kojic acid inhibits the catecholase activity of tyrosinase .Melanocytes treated with kojic acid become nondendritic, with a decreased melanin content. Kojic acid is used in concentrations ranging from 1-4%. Although effective as a skin-lightening gel, it has been reported to have high sensitizing potential and may cause irritant contact dermatitis. In a study comparing glycolic acid/kojic acid combination with glycolic acid/HQ, no statistical difference in efficacy was reported between kojic acid and HQ; however, the kojic acid preparation was reported to be more irritating. To decrease the irritation from kojic acid, it is combined with a topical corticosteroid. In a comparison study, 2% HQ, 10% glycolic acid, and 2% kojic acid decreased hyperpigmentation in patients with melasma .

5-Mequinol (4-hydroxyanisole)

4-hydroxyanisole (4HA) is cytotoxic to melanocytes. Reports indicate it is clinically effective in inhibiting melanogenesis when used as a combination of 2% 4HA cream and 0.01% retinoic acid. The authors reported minimal local skin irritation with this combination. Two percent 4HA alone did not produce significant hypopigmentation. Mequinol is used in Europe and in the United States for the treatment of solar lentigines.

6-Arbutin (HQ-beta-D-glucopyranoside)

arbutin has been shown to inhibit melanin synthesis by inhibition of tyrosinase activity. Inhibition of melanosomal tyrosinase activity, rather than suppression of the synthesis and expression of this enzyme, appears to be the mechanism of action. Inhibition of melanin synthesis (approximately 39%) occurs at a concentration of 5 X 105 mol/L.

a-Alpha Arbutin:
It is the epimer of arbutin, and research has proven that it has a stronger inhibitory action than that of (beta) arbutin. Though it is a very expensive ingredient to manufacture, even at very low concentrations, a-arbutin has shown to inhibit the activity of tyrosinase. Alpha Arbutin's inhibitory mechanism is different from that of arbutin and can be up to 10 times more effective.
b-Beta-Arbutin (Bearberry Extract):
Beta-Arbutin is often referred to as just Arbutin. As a natural extract found in bearberry (Uva Ursi) plants, Arbutin also provides a skin lightening effect on the skin by inhibiting tyrosinase activity. Though arbutin is a natural derivative of hydroquinone, it does not possess the same risks or side effects. Arbutin has been shown to be a very safe ingredient and does not break down into hydroquionone very readily.

7-Paper mulberry

This tyrosinase inhibitor was isolated from a plant herbal extract. A comparison of the tyrosinase inhibition of paper mulberry with kojic acid and HQ reveal that the IC50 (ie, the concentration causing 50% inhibition of the activity of tyrosinase) is 0.396%, compared with 5.5% for HQ and 10.0% for kojic acid.

8-Glabridin (licorice extract)

Glabridin is the main ingredient in licorice extract. glabridin inhibited tyrosinase activity of melanocytes without cytotoxicity. They further showed that UV-B–induced pigmentation and erythema were inhibited by topical application of 0.5% glabridin. The anti-inflammatory properties of glabridin were attributed to inhibition of superoxide anion production and cyclooxygenase activity. A combination product of 0.4% licorice extract, 0.05% betamethasone, and 0.05% retinoic acid was effective in the treatment of melasma.

9-Arctostaphylos patula and Arctostaphylos viscida

The leaves of these 2 Arctostaphylos plants have been reported to be potent inhibitors of tyrosinase.These 2 extracts not only inhibited the production of melanin from dopachrome, but also exhibited superoxide dismutaselike activity

Niacinamide is commonly known as Vitamin B3 and is an effective skin lightening compound that works by inhibiting melanosome transfer from melanocytes to keratinocytes. Often this ingredient works best when combined with other skin lightening treatments. Niacinamide (Vitamin B3) is also known to be effective in reducing acne.

11-Glycolic Acid:
Glycolic Acid is a AHA (alpha hydroxy acid) which promotes exfoliation and a natural brightening of the skin tone. By encouraging cell turnover, glycolic acid not only evens out skin discolorations, but also helps to minimize fine lines and wrinkles. AHA's such as Glycolic Acid can assist other ingredients in skin lighteners by allowing

them to penetrate farther into the skin.

12-Lactic Acid:
Also an AHA (alpha hydroxy acid), Lactic acid mimics the properties of Glycolic acid but is typically better suited for individuals with sensitive skin. AHA's such as Lacic Acid can assist other ingredients in skin lighteners by allowing them to penetrate farther into the skin.

13-Lemon Juice Extract:

nature's most potent skin bleaching ingredients. Unfortunately it is also very irritating to the skin and should only be used at small concentrations in skin lighteners. Lemon juice is also known to be extremely drying to the skin if applied directly.

Emblica is a patented composition extracted from the plant Phyllanthus emblica. The extract uses a multilevel cascade of antioxidant compounds resulting in a long-lasting and stable antioxidant activity. Recent studies have shown that this natural antioxidant also provides significant skin lightening properties when used in moderate concentrations

15-Vitamin C:
Vitamin C is a natural antioxidant that occurs in many different forms (some stable and others unstable) each with distinct properties. Several of these forms have been shown to reduce melanin formation and provide a skin whitening effect when applied topically. These include l-ascorbic acid, magnesium ascorbyl phosphate and sodium ascorbyl phosphate. These forms when used individually or together can assist in slowing down hyperactive melanocytes and thus resulting in lighter skin.

16-Mercurous chloride:

Mercury poisoning is the result of the use of mercury-based skin-whiteners.Mercury is linked to kidney, nervous system, and gastrointestinal disorders. Prolonged contact with Mercury also leads to skin rashes, mood swings, memory loss, and muscle weakness. signs of disease in the brain, liver, and kidney of all mice treated with a “skin-whitening” cream containing mercury, even among those treated once a week, with an increase in disease corresponding to the number of applications. Mercury exposure to the womb is especially harmful, causing nervous system and brain damage to the developing baby. It is linked to neurological effects such as language, fine motor skills, memory, and cognitive thinking

l Eldoquin cream

l Hydroquinone..........2%

l Beauti-Gel

l Hydroquinone..........2%Retenoic acid..........0.05%.....Tretinoin has been used to enhance the efficacy of HQ.

l Moonlight cream

l Arbutin.....Petroseinium Sativum(Parsley seeds).....contain large amount of vitamin A&C,Iron,calcium and magnesium(nutrients for the skin).Licorice extract....L-Ascorbic acid.....stimulates collagen synthesis and prevent UV immunosuppression.Tetanium dioxide....sun screen

l Koji-C cream

l kojic acid dipalmitate.........2%Tretinoin(Vitamin A).........increase collagen synthesisTocopheryl acetate(Vitamin E)........antioxidant.Ascorbyl palmitate(Vitamin C)........Octinoxate(Parsol MCX)........sunscreen agent.

l SkinMix cream

l Licorice extract.........

l Ascorbic acid.........

l Vitamin C.........

l Titanium dioxide........

2 significant brand products

1-Derma-clinic whitening cream unique formulation designed for skin lightening or whitening purpose.

2-free from HYDROQUINONE or KOJIC ACID.It is based on high content of stable form complex of botanical extracts called BIOWHITE.3-BIOWHITE is a complex composed of 4 vegetal extracts:

a...... Mulberry Extract-has the basic molecules to stop tyrosinase production.Also has anti-inflammatory effects.

b......Saxifrage Extract-extracts of over 370 plant species with anti-free radical action,so preventing skin damage caused by UV radiation.Also has Arbutin.

c......Scutellaria Root Extract-has flavonoids molecules to stop tyrosinase production.

d.......Grape Extract-A high concentration of Hydroxy Acid which promotes cell-renewal.Works in synergy with other ingredients to combat pigmentation.

.......1% BIOWHITE can inhibt tyrosinase activity by 97%.

.......The only non cytotoxic whitening complex.

4-Contains plant extracts that exfoliate dark surface cells and promote healthy cell renewal.

5-Also contain effective UV absorber sun screen to shield the skin from UV radiation.

6-It is highly stable and clinically proven to stop pigmentation,lighten skin tone and improve complexion with top efficacy.

7-It helps to reduce the appearance of fine lines age spots,frecles and gives brighter complexion.

8-It is a very good deep radiance booster.

9-Produced by microsphere(THALASPHERE)technology:A manufacturing technology where the active ingredients are delivered in a collagen and glycosaminoglycan sphere that reaches the stratum corneum in significant quantities even after rinsing and drying and provides a continous long lasting whitening effect.

2-Photoderm-White Objective.....(The White Objective innovation)

combination of specific active ingredients guarantee a multiple targeted attack on the main cause of cutaneous pigmentation.

inhibitory action on the 4 stages of pigmentation process.

1-Stimulation of the melanin-producing cells is limited:

a-sun filters ensure a very high level of protection and eleminate the stimulation of melanocytes by UV rays.

b-andrographolid and melanostatin curb the stimulation by mediators and slow down pigmentation.

2-The production of melanin is slowed:

a- glabridine(licorice extract)and azeilate of lysine,inhibit the action of tyrosinase.

3-The transfer of melanin is limited:

a- Vitamin PP reduces the transfer of melanin to the upper layers of the epidermis.

4-The migrating melanin is reduced:

a-Vitamin C reduces the melanin as it is migrated to the upper layers of the epidermis,it also minimize the action of the free radicals.Time released,it ensures prolonged action.

b-The glycolic acid ensures gentle peeling effect by eleminating cells already loaded with melanin.


Lasers function by emitting a monochromic, high-intensity, coherent energy source that is absorbed by water, hemoglobin, and melanin in the skin, referred to as chromophores. The absorption of energy destroys the chromophores. The wavelength of the laser dictates the depth of laser penetration and the chromophores targeted. Based on the absorption spectrum of melanin, the Q-switched ruby laser (694 nm) and the Q-switched Nd:Yag laser (1064 nm) are the lasers of choice for the treatment of hyperpigmented lesions such as lentigines and postinflammatory hyperpigmentation. Adverse effects from laser treatment include discomfort, redness, mild swelling, and postinflammatory hyperpigmentation. Patients should always have a test spot performed before a full treatment.

Intense pulsed light

A recent derivative of laser treatment, in which high-intensity pulses of a broad wavelength (515-1200 nm) of light deliver energy to the skin. The energy of IPL is delivered to the dermis and is absorbed by the chromophores. IPL has been shown to work well for the treatment of lentigines, but the therapy has not been optimized for the treatment of melasma.Adverse effects of IPL treatment include pain, local irritation, and postinflammatory hyperpigmentation.

Fractional photothermolysis

Fraxel works by thermal damage to microscopic zones of the epidermis and dermis. With a single Fraxel treatment, an estimated 15-20% of the skin undergoes laser resurfacing, and the surrounding normal skin is postulated to help in the healing process. Based on the fraction of skin that experiences thermal damage, it is hypothesized that the skin will have less damage and thus will require less healing ("downtime") between treatments. A case report describing Fraxel treatment showed a marked reduction in hyperpigmentation in a white woman after 2 treatments, and no adverse effects were reported. Furthermore, a case series of 10 patients with melasma documented a 75-100% improvement of melasma in 5 of 10 patients based on physician and patient assessments.


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