Arbutin

beta-Arbutin, also known as β-arbutin or by its International Nomenclature of Cosmetic Ingredients (INCI) name, arbutin, is a glycosylated derivative of hydroquinone. β-Arbutin is naturally present in the leaves and bark of a variety of plants, notably the bearberry plant, Arctostaphylos uva-ursi. Utilized as a biosynthetic active ingredient in topical treatments for skin lightening, β-arbutin is aimed at addressing hyperpigmentation issues. Its mechanism of action involves inhibiting the activity of tyrosinase, an essential enzyme for melanin synthesis in the human skin, thereby leading to a reduction in hyperpigmentation. It is important to distinguish β-arbutin from its structurally similar stereoisomer, α-arbutin, which exhibits similar effects in clinical applications.

Properties
Arbutin is a compound where a glucose molecule, specifically -glucose, is chemically bound to hydroquinone. In aqueous solutions, glucose can exist in one of three stereoisomeric forms: α, β, or γ, with the β-anomer being the predominant form. The standard known form of arbutin, β-Arbutin, has a molecular formula of C12H16O7 and a molecular weight of 272.25g/mol. Its stereoisomers, α-arbutin and γ-arbutin, share the same molecular formula and weight but are distinct in their atoms' spatial arrangement.

β-Arbutin is soluble in water, presenting typically as a white powder that remains stable under standard storage conditions. It exhibits stability in both ethanol and water and demonstrates resistance to light exposure. When dissolved in water, β-arbutin may undergo hydrolysis, converting to hydroquinone, which can subsequently oxidize to benzoquinone.

Occurrence and preparation
The compound is naturally occurring and can be extracted from several plant species. Traditionally extracted from the bearberry plant (Arctostaphylos uva-ursi), it also occurs in high levels in plants in the families of Ericaceae and Saxifragaceae. Others include the pear (Pyrus spp.), and certain species of wheat. It is also found in very small quantities in Viburnum opulus, Bergenia crassifolia and Schisandra chinensis.

Synthetically, it can also be prepared from the reaction of acetobromoglucose and hydroquinone in the presence of an alkali.

Uses
The main application of β-arbutin is in the cosmetic industry, where it is incorporated into various skin care products, including creams, serums and lotions, aimed at lightening skin tone and correcting hyperpigmentation. Its efficacy and safety profile make it a sought-after ingredient for products targeting solar lentigo, freckles, melasma, and other forms of hyperpigmentation.

Herbal medicine
For centuries, β-arbutin has been used in phytotherapy, or herbal medicine. Extracted from the leaves of bearberry plants, it is used as a mixture with other herbal drugs as a treatment for urinary tract infections.

Regulation of melanin synthesis
β-Arbutin acts as an enzyme inhibitor of cellular tyrosinase by inactivating it. Tyrosinase is an enzyme needed in melanin synthesis in the melanin producing cell of the skin, the melanocyte. By reducing the activity of tyrosinase, β-arbutin reduces the synthesis of melanin, leading to a lighter skin tone and the diminished appearance of hyperpigmentation. It is not as potent an inhibitor of tyrosinase as α-arbutin.

It has also been shown act as a substrate for tyrosinase. Tyrosinase catalyses the hydroxylation of tyrosine, an amino acid, to -DOPA (levodopa) and the oxidation of -DOPA to dopaquinone which is then further metabolised to melanin. β-Arbutin is thought to have structural similarities to the substrate tyrosine, and this may inhibit the activity of tyrosinase.

Decomposition into hydroquinone
Conflicting evidence shows that β-arbutin may also work by being decomposed into hydroquinone. If this occurs, the amount of hydroquinone created by decomposition would be small and its contribution to inhibiting the creation of melanin as small.

Safety and regulation
β-Arbutin is generally considered safe for topical application in cosmetic products. However, its usage concentrations in the European Union (EU) are restricted by the European Commission Scientific Committee on Consumer Safety to 7% in facial creams, provided the contamination of hydroquinone remains below 1 ppm.

Skin-lightening agent
Bearberry extract is used in skin lightening treatments designed for long term and regular use. An active agent in brands of skin lightening preparations, it is more expensive than traditional skin lightening ingredients like hydroquinone, which is now banned in many countries. In vitro studies of human melanocytes exposed to arbutin at concentrations below 300 μg/mL reported decreased tyrosinase activity and melanin content with little evidence of cytotoxicity.

Risks
Arbutin is glucosylated hydroquinone, and may carry similar cancer risks, although there are also claims that arbutin reduces cancer risk. The German Institute of Food Research in Potsdam found that intestinal bacteria can transform arbutin into hydroquinone, which creates an environment favorable for intestinal cancer.