β-Arbutin, also known by its

International Nomenclature of Cosmetic Ingredients The International Nomenclature of Cosmetic Ingredients (INCI) are the unique identifiers for cosmetic ingredients such as waxes, oils, pigments, and other chemicals that are assigned in accordance with rules established by the Personal Care P ...

(INCI) name, arbutin, is a

glycosylated Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

derivative of

hydroquinone Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''para' ...

. β-Arbutin is naturally present in the leaves and bark of a variety of plants, notably the bearberry plant, ''

Arctostaphylos uva-ursi ''Arctostaphylos uva-ursi'' is a plant species of the genus ''Arctostaphylos'' widely distributed across circumboreal regions of the subarctic Northern Hemisphere. Kinnikinnick (from the Unami language for "smoking mixture") is a common name in ...

''. Utilized as a biosynthetic active ingredient in

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

treatments for skin lightening, β-arbutin is aimed at addressing

hyperpigmentation Hyperpigmentation, also known as the dark spots or circles on the skin, is the darkening of an area of Human skin, skin or nail (anatomy), nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or ...

issues. Its mechanism of action involves inhibiting the activity of

tyrosinase Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper–Mason pathway. Firstly, the hydroxy ...

, an essential enzyme for

melanin Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes. There are ...

synthesis in the

human skin The human skin is the outer covering of the body and is the largest organ of the integumentary system. The skin has up to seven layers of ectodermal tissue (biology), tissue guarding Skeletal muscle, muscles, bones, ligaments and organ (anato ...

, thereby leading to a reduction in hyperpigmentation. It is important to distinguish β-arbutin from its structurally similar

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

, α-arbutin, which exhibits similar effects in clinical applications.

Properties

Arbutin is a compound where a

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

molecule, specifically -glucose, is chemically bound to

. In aqueous solutions, glucose can exist in one of three stereoisomeric forms: α, β, or γ, with the β-

anomer In carbohydrate chemistry, a pair of anomers () is a pair of near-identical stereoisomers or diastereomers that differ at only the anomeric carbon, the carbon atom that bears the aldehyde or ketone functional group in the sugar's open-chain for ...

being the predominant form. The standard known form of arbutin, β-Arbutin, has a

molecular formula A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as paren ...

of C₁₂H₁₆O₇ and a

molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

of 272.25 g/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 Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

, converting to

, which can subsequently

oxidize Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

to benzoquinone.

Occurrence and preparation

The compound is naturally occurring and can be extracted from several plant species. Traditionally extracted from the bearberry plant (''

''), it also occurs in high levels in plants in the families of

Ericaceae The Ericaceae () are a Family (biology), family of flowering plants, commonly known as the heath or heather family, found most commonly in acidic and infertile growing conditions. The family is large, with about 4,250 known species spread acros ...

and

Saxifragaceae Saxifragaceae is a family of Herbaceous plant, herbaceous Perennial plant, perennial flowering plants, within the core eudicot Order (biology), order Saxifragales. The Taxonomy (biology), taxonomy of the family has been greatly revised and the ...

. Others include the

pear Pears are fruits produced and consumed around the world, growing on a tree and harvested in late summer into mid-autumn. The pear tree and shrub are a species of genus ''Pyrus'' , in the Family (biology), family Rosaceae, bearing the Pome, po ...

(''Pyrus spp.''), and certain species of

wheat Wheat is a group of wild and crop domestication, domesticated Poaceae, grasses of the genus ''Triticum'' (). They are Agriculture, cultivated for their cereal grains, which are staple foods around the world. Well-known Taxonomy of wheat, whe ...

. It is also found in very small quantities in ''

Viburnum opulus ''Viburnum opulus'', commonly known as the guelder-rose, or guelder rose (), is an Old World species of flowering plant in the family Adoxaceae. Description ''Viburnum opulus'' is a deciduous shrub growing to tall. The leaves are opposite, th ...

,'' '' Bergenia crassifolia and

Schisandra chinensis ''Schisandra chinensis'', whose fruit is called magnolia berry or five-flavor fruit (, in , ), is a vine plant native to forests of Northern China, the Russian Far East and Korea. Wild varieties are also found in Japan. It is hardy in USDA Zone ...

''. Synthetically, it can also be prepared from the reaction of acetobromoglucose and

in the presence of an

alkali In chemistry, an alkali (; from the Arabic word , ) is a basic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a soluble base has a pH greater than 7.0. The a ...

Uses

The main application of β-arbutin is in the

cosmetic industry The cosmetic industry describes the industry that manufactures and distributes cosmetic products. These include colour cosmetics, like foundation and mascara, skincare such as moisturisers and cleansers, haircare such as shampoos, conditioners a ...

, where it is incorporated into various skin care products, including creams, serums and lotions, aimed at lightening skin tone and correcting

. Its efficacy and safety profile make it a sought-after ingredient for products targeting solar lentigo,

freckle Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ov ...

melasma Melasma (also known as chloasma faciei,James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . or the mask of pregnancy when present in pregnant women) is a tan or dar ...

, and other forms of hyperpigmentation.

Herbal medicine

For centuries, β-arbutin has been used in

phytotherapy Herbal medicine (also called herbalism, phytomedicine or phytotherapy) is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. Scientific evidence for the effectiveness of many herbal treatments ...

, 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 A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra ( urethritis) while upper urinary tract infections affect the kidney (pye ...

Mechanism of action

Regulation of melanin synthesis

β-Arbutin acts as an

enzyme inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its Enzyme activity, activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which Substrate (biochemistry), substrate molecules are converted ...

of cellular

by inactivating it. Tyrosinase is an enzyme needed in

synthesis in the melanin producing cell of the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

, the

melanocyte Melanocytes are melanin-producing neural-crest, neural crest-derived cell (biology), cells located in the bottom layer (the stratum basale) of the skin's epidermis (skin), epidermis, the middle layer of the eye (the uvea), the inner ear, vagina ...

. 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 Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

for tyrosinase. Tyrosinase catalyses the

hydroxylation In chemistry, hydroxylation refers to the installation of a hydroxyl group () into an organic compound. Hydroxylations generate alcohols and phenols, which are very common functional groups. Hydroxylation confers some degree of water-solubility ...

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

, an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

, to -DOPA (levodopa) and the

oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

of -DOPA to dopaquinone which is then further metabolised to

. 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

application in cosmetic products. However, its usage concentrations in the European Union (EU) are restricted by the

European Commission The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...

Scientific Committee on Consumer Safety The Scientific Committee on Consumer Safety (SCCS) is one of the independent scientific committees managed by the Directorate-General for Health and Consumer Protection of the European Commission, which provide scientific advice to the commission ...

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

, which is now banned in many countries. In vitro studies of human

melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hea ...

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

, and may carry similar cancer risks, although there are also claims that arbutin reduces cancer risk.Bowman, Lee. July 25, 2005. Scripps Howard News Service
High yuck factor not necessarily good for us anymore
The German Institute of Food Research in

Potsdam Potsdam () is the capital and largest city of the Germany, German States of Germany, state of Brandenburg. It is part of the Berlin/Brandenburg Metropolitan Region. Potsdam sits on the Havel, River Havel, a tributary of the Elbe, downstream of B ...

found that intestinal bacteria can transform arbutin into hydroquinone, which creates an environment favorable for

intestinal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...

References

{{reflist Phenol glucosides Skin whitening 4-Hydroxyphenyl compounds