Innovating Natural Actives for Your Brands® 
Every woman seeks to have flawless skin free from age spots, blemishes and scars. Whatever the color of the skin, it is susceptible to damage due to environmental agents, physiological changes and psychological factors. The demand for "skin fairness products" is rooted in the need to eliminate localized hyperpigmentation as well as to lighten the general skin tone.

The motives behind the use of skin lightening products vary considerably between cultures. In Western countries, people wish to eliminate or inhibit the development of irregular pigmentation including melasma (chloasma or localized discoloration), age spots ( Lentigo senilis ) or liver spots (associated with sun damage or aging sometimes appearing as raised spots or Seborrheic keratoses ) and freckles ( Lentigo aestiva ). In Asia , a lighter skin color is associated with beauty and aristocracy. Therefore, in Asian countries, skin lightening products are used with the intent to lighten and brighten the skin tone.


Factors that influence Skin Color  
Skin pigmentation is influenced by several factors like:

•  Hemoglobin in the blood vessels
•  Carotenoids in the dermis
•  Particularly, the dark pigment, melanin in the epidermis (Figure 1).

Two forms of melanin are produced in the epidermis: phenomelanin, which is red to yellow in color, and eumelanin which is dark brown to black. The relative proportions of these also influence skin color. In addition, individuals differ in the number and size of melanin particles.


Production of Melanin  

Melanin biosynthesis (melanogenesis) is influenced by genetics, environmental factors, diet and medication. The production of melanin by specialized cells called melanocytes (in the basal layer of the epidermis in light skinned people and in the basal as well as horny layer in dark skinned people) occurs through the action of the enzyme tyrosinase. The rate-limiting step in melanogenesis is the conversion of L-tyrosinase to melanin, through the action of tyrosinase. Copper and oxygen act as catalysts. Other enzymes also control melanin production, particularly in the presence of sulfur. These include the following:

•  Dopachrome oxidoreductase which controls melanogenesis in the absence of tyrosinase. It helps to convert dopachrome into 5, 6-dihydroxyindole.
•  Alpha-glutamyl transpepsidase which helps to maintain the balance in the biosynthesis of eumelanin and pheomelanin.

The currently accepted scheme for melanin biosynthesis is shown in Figure 2. Variation in skin pigmentation is attributed to the levels of melanin produced and the number of melanocytes present. Although light skinned and dark skinned people may have the same number of melanocytes present, the rate of melanin production is greater in darker skin tones. Additionally, the melanin present in the epidermal layers of darker skins is resistant to enzymatic degradation. Increased production of melanin on one side of the skin and dramatically reduced decomposition of melanin on the other side results in darker skin tones, in light skinned people.

Melanin granules synthesized in the melanocytes are then transferred from the cytoplasm of the melanocytes to the basal cytoplasm of the keratinocytes. They thus form a protective covering in the inner layers of the epidermis, absorbing UV rays and inhibiting their penetration.


Controlling Melanin Synthesis  

Various types of inflammatory mediators such as leukotrienes and prostaglandins, cytokines and growth factors may influence melanin synthesis by affecting the proliferation and functioning of melanocytes. This explains why inflammatory diseases often induce hypopigmentation or hyperpigmentation. The enzyme, protein kinase C that phosphorylates proteins may also influence the growth and differentiation of melanocytes. Cytokines such as endothelins (also known as vasoconstrictive peptides) are also reported to accelerate melanogenesis.

Thus tyrosinase inhibitors, agents that increase keratinocyte turnover, agents that inhibit the hormone melanotropin, physical sunscreens, reducing agents that convert dopaquinone to DOPA, indole-blockers that inhibit the formation of intermediates in melanin biosynthesis, antioxidants that chelate metal ions (which catalyze tyrosinase activity), cytokine regulators and genetic manipulation would all be beneficial in controlling melanin synthesis.

Skin lightening cosmeceuticals  

The toxicity associated with hydroquinone use, induced researchers to identify less dangerous botanicals with comparable activity. The general modes of action include inhibition of the formation of melanosomes, inhibition of tyrosinase biosynthesis, and inhibition of melanin biosynthesis and interference of the transfer of melanosomes into the keratinocytes. Some agents also have a chemical effect on melanin with an increase in the degradation of melanosomes in the keratinocytes. Antioxidants such as ascorbic acid and others help to decompose preformed melanin. Hyperpigmentation due to UVA and UVB damage may also be addressed by preventive measures using antioxidant compounds with sunscreen effect and free radical scavenging action.
Research efforts are generally aimed at achieving one or more of the following effects:

  • Regulation/inhibition of tyrosinase, dopachrome oxidoreductase and dopachrome tautomerase involved in melanogenesis
  • Regulation of the cytokine network including endothelin
  • Regulation of genes related to melanogenesis
  • Combinations of the above approaches

Tyrosinase inhibitors such as Arbutin (from the leaves of the common bearberry, ( Arctophylos urva ursi and other plants), Glabridin from licorice ( Glycyrrhiza glabra roots), ascorbic acid and its derivatives, Kojic acid (a bacterial carbohydrate metabolite) are better tolerated than hydroquinone. Aloesin from Aloe is reported to be a non-competitive inhibitor of tyrosinase, affecting the action of tyrosinase complex in the substratum and reducing the conversion of DOPA into melanin.

Arbutin and Kojic acid inhibit tyrosinase directly, while L-ascorbic acid and its derivatives are believed to act as reducing agents on intermediates in melanin biosynthesis at various points in the oxidation chain reaction from tyrosine/DOPA to melanin. Green tea is also reported to be a competitive tyrosinase inhibitor based on in vitro studies The gallocatechin moiety in the major catechin constituents epicatechin gallate, epigallocatechin gallate and gallocatechin gallate is reported to be responsible for this effect. Additionally, the antioxidant, anti-inflammatory and UV protectant effects of green tea catechins are well-documented. Paper mulberry extract (from the root bark of Broussonetia kazinoki x B. papyrifera ) also contains active depigmenting agents, which were shown to be more efficacious than hydroquinone (IC 50 of 2.5 mg/ml against 5.5 mg/ml for hydroquinone). Soy extract is also reported to have moderate skin lightening action in solar lentigenes (hyperpigmentation due to sun exposure).

An extract from matricaria ( Chamomilla recutita ) is reported to contain an endothelin inhibitor. Endothelin inhibitors are reported to work faster than tyrosinase inhibitors on account of the fact that their mechanism of action is outside the melanocyte cell membrane. Tyrosinase inhibitors on the other hand have to cross four barriers - the stratum corneum (outer epidermal layer), deeper epidermal layers, the melanocyte membrane and the melanosome membrane.

The mechanism of action of the major skin lightening agents is summarized in

Table 1: Mechanism of action of depigmenting agents:


Examples of active agents


UV absorber


Does not directly affect pigmentation, only blocks UV light

Free radical scavenging


Lower whitening effect (indirect mechanism)

Tyrosinase synthesis inhibitor

Glucosamine, galactosamine, manosamine, and others

No specificity to tyrosinase, have potent cytotoxic effect

Tyrosinase inhibitor

Hydroquinone, ascorbic acid derivatives, Kojic acid, arbutin, glutathione, mulberry extract, licorice extract

Stability, availability and safety issues need to be considered

Interrupts intermediates in melanin biosynthesis

Kojic acid

Mechanism of action not fully interpreted

Cytotoxic effects to melanocytes


High dermal toxicity

Reduce preformed melanin

Tocopherol, vitamin C derivatives

Mechanism not clear

Endothelin inhibitor

Chamomilla recutita

Under research


Sabinsa Products for Skin Lightening  

Licorice Extract (Glabridin 4% & 40%)

  Tetrahydrocurcuminoids CG      



Galanga Extract


Ellagic Acid






Disclaimer: The information on this website is for general purposes only. Users are urged to check the validity of patents if any, on any of these items for their intended use.

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