cosmetology

Melanogenesis modulators

Tyrosinase inhibitors

Since tyrosinase controls the biosynthesis of melanin in epidermal melanocytes, acting on the activity of this enzyme represents a valid strategy for correcting hyperpigmentation defects. Examples of compounds with this type of mechanism of action are:

Kojic acid

Kojic Acid is a depigmenting agent of fungal origin. It inhibits tyrosinase, chelating copper in the active site. However, it is an unstable molecule that oxidizes in contact with air and light, losing its activity and giving the product in which it is inserted a dark color. It can cause sensitization problems, contact allergies and dermatitis.

Hydroquinone

Hydroquinone is a natural compound that can be found in many plants and in products such as coffee, tea and beer. It decreases the activity of tyrosinase in several ways: by interacting with copper in the active site of the enzyme, altering the functioning of melanosomes, causing oxidative damage to the lipid membrane and melanocyte proteins. It is a very effective compound, but it can cause, especially at high concentrations, different side effects, such as skin irritation, contact dermatitis, cytotoxicity, exogenous ochronosis (browning of the treated area). It is generally used in concentrations of 2%, but use as a lightening of the skin is limited to dermatological prescriptions and use in cosmetic products is prohibited by law.

Arbutin

Arbutin is a natural glucoside of hydroquinone found in bearberry plants, blueberries, raspberries and many types of pears. It inhibits the enzyme tyrosinase with a mechanism not yet clarified, different from that of hydroquinone, since it does not intervene either on synthesis or on the expression of the enzyme. A derivative of arbutin semisynthesis, desoxyarbutin, has demonstrated an ability to inhibit tyrosinase already at concentrations much lower than those required with hydroquinone and arbutin.1 It also has a good antioxidant capacity, thus helping to reduce the amount of free radicals generated by UV rays.

Azelaic acid

Azelaic acid is a bicaboxylic acid naturally produced by some fungi; inhibits the formation of melanin in cases of melanocyte hyperactivity: photosensitization melanosis, melasma, post-inflammatory melanosis. Lightening properties are also attributed to octadecenedioic acid, also a bicarboxylic acid, which has proved effective in a considerably lower percentage (2%) than that used for azelaic acid (20%).

Polyphenols

Polyphenols are molecules widely distributed in nature, which can be found in different parts of many plants (stems, leaves, roots, flowers). They are compounds that have lower side effects than Arbutin and Kojic Acid, so they are more suitable for cosmetic use, even if the results and effectiveness are often based on studies carried out only in vitro or on laboratory animals.

The lightening activity of flavonols is due to a competitive mechanism of action on tyrosinase, which - thanks to the presence of a 3-hydroxy-4-ketonic residue - plays an essential role in the chelation of copper. This group includes such compounds as:

  • Ellagic Acid, extracted from plants such as pomegranate, strawberry, green tea and eucalyptus, which showed in vitro an inhibitory activity of the tyrosinase enzyme comparable to that of Arbutin and Kojic Acid2.
  • Mulberroside F, extracted from the leaves of Morus alba, has been shown to be four times more potent than the Kojic acid in inhibiting the synthesis of melanin and the activity of the enzyme 3.

Licorice Extracts

Licorice extracts (especially Glycirrhiza) demonstrate good ability to lighten the skin thanks to the presence of isoflavonoids . Among these, Glabridin has been shown to exert an action on tyrosinase fifteen times higher than that of Kojic Acid and depigmentation is higher than that obtained with Arbutin. Recently Gliasperina C was isolated with double activity compared to Glabridin . Isoflavonoids also have strong antioxidant and anti-inflammatory properties, and are able to inhibit the production of free radicals.

Still belonging to the family of Glycirrhiza, compounds effective in inhibiting the enzyme tyrosinase with a competitive mechanism, are the chalcones : Licuraside, Isolirquitina, Licocalcone A. The latter has shown to possess an activity equal to 5 times that of Kojic Acid. From a chemical point of view, it is believed that the inhibition of the enzyme is due to the residue of 4-resorcinol (isomer of hydroquinone), characteristic of the structure of chalcones.4 In vivo studies that ascertain the real effectiveness of this class of however, compounds are still limited.

Resveratrol

Among the most effective polyphenols in inhibiting the functionality of the tyrosinase enzyme we find the stilbenes, low molecular weight phenolic compounds. Oxyresveratrol is a hydroxystilbene obtained from the plant of Morus alba, which has shown an inhibiting action of tyrosinase 30 times higher than kogic acid, thanks to the presence in its structure of 4-Resorcinol (isomer of hydroquinone, analogous to that contained in the aforementioned chalcones).

Resveratrol, lacking this structure, has a significantly lower inhibitory activity. It is a safe molecule, free of irritating effects.

cumarine

The coumarins such as Aloesina, a glycosylated compound extracted from the Aloe vera plant, are inhibitors of the tyrosinase enzyme capable of blocking the production of melanin in melanocyte cultures. The powerful antioxidant action, in synergy with the lightening action, makes Aloe a plant potentially useful in the treatment of hyperpigmentation disorders.

1 Boissy RE, Visscher M, DeLong MA. Deoxyarbutin: a reversible novel tyrosinase inhibitory with effective in vivo skin ligthening potency . Exp Dermatol. 2005; 14: 601-8

2 Shimogaki H, et al. In vitro and in vivo evaluation of ellagic acid on melanogenesis ihhibition. Int J Cosmet Sci. 2000; 22: 291

3 Lee SH, et al. Mulberroside F isolated from leaves of Morus alba inhibits melanin biosynthesis. Biol Pharm Bull . 2002; 25: 1045-1048

4 Ohgichi K, Tanaka T, Kido T, Baba K , et al . Effects of hydroxystilbene derivates on tyrosinase activity. Biochem biophys commun. 2003; 307: 861-863