ALPHA-ARBUTIN

Alpha-Arbutin is used in the cosmetic and pharmaceutical industries for its skin lightening effects, treatment of hyperpigmentation, and as a possibly safer alternative to hydroquinone.
Alpha-Arbutin is used brightening serums, anti-pigmentation creams, spot treatments, products for melasma, solar lentigo (age spots), post-inflammatory hyperpigmentation.

CAS Number: 84380-01-8
EC number: 440-470-8
MDL number: MFCD09838262
Molecular Formula: C12H16O7

SYNONYMS:
4-Hydroxyphenyl α-D-glucopyranoside, Hydroquinone O-α-D-glucopyranoside, alpha-Arbutin, 84380-01-8, 4-Hydroxyphenyl a-D-glucopyranoside, alpha arbutin, 4-hydroxyphenyl alpha-D-glucopyranoside, a-Arbutin, UNII-72VUP07IT5, (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-(4-hydroxyphenoxy)oxane-3,4,5-triol, 72VUP07IT5, ORISTAR AAT, alpha-D-Glucopyranoside, 4-hydroxyphenyl, CHEBI:29710, DTXSID20233358, (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-(4-hydroxyphenoxy)tetrahydro-2H-pyran-3,4,5-triol, PubChem16460, AC1L4KBI, Alpha Arbutine, Alfa Arbutina, alpha-Arbutoside, MFCD09838262, I+/--Arbutin, 4-Hydroxyphenyl-alpha-D-glucopyranoside, .ALPHA.-ARBUTIN, ?-ARBUTIN, ALPHA-ARBUTIN [INCI], SCHEMBL435261, CHEMBL226495, ALPHA-ARBUTIN [WHO-DD], 4-hydroxyphenyl-D-lucopyranoside, DTXCID20155849, alpha-Arbutin, analytical standard, AMY22497, HY-N3002, a-D-Glucopyranoside, 4-hydroxyphenyl, s5112, AKOS015905235, CCG-267174, DB14109, N-CYCLOPROPYL-N-HYDROXYGUANIDINE, (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-(4-hydroxyphenoxy)tetrahydropyran-3,4,5-triol, 1ST40211, AC-34884, AS-15466, CS-0022901, P-HYDROXYPHENYL-alpha-D-GLUCOPYRANOSIDE, EN300-7406351, P-HYDROXYPHENYL-.ALPHA.-D-GLUCOPYRANOSIDE, 4-HYDROXYPHENYL-.ALPHA.-D-GLUCOPYRANOSIDE, A840768, W-203913, Q27110235, (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-(4-hydroxyphenoxy)tetrahydropyran-3,4,5-triol, alpha-Arbutin, Alpha-Arbutin, 4-Hydroxyphenyl-alpha-D-glucopyranoside, CAS No. 84380-01-8, EC No. 617-561-8, α-Arbutin, Alpha-Arbutin, 4-Hydroxyphenyl-α-D-glucopyranoside, Hydroquinone-α-glucopyranoside, 4-Hydroxyphenyl alpha-gluco-hexopyranoside, Alpha-Arbutin (INCI), Arbutin (α-anomer)

Alpha-Arbutin is extremely sensitive to degradation in the presence of water if the pH of the formulation is not ideal.
The pH of Alpha-Arbutin has been shown to be the most suitable pH to minimize degradation of Alpha Arbutin.
Alpha-Arbutin, is a glycosylated hydroquinone, and an anomer of the naturally occurring arbutin.

Arbutin is a naturally occurring compound found in many plant sources such as bearberry, mulberry, and pomegranate.
"Arbutin" and "alpha-arbutin" are often used synonymously or interchangeably; alpha-arbutin is simply the chemically synthesized version most often found in skin-care products.

There's another variant, beta-arbutin, but don't bother seeking this one out.
Studies have shown that alpha-arbutin is over 10 times more effective than beta-arbutin.
Alpha-Arbutin, also called Hydroquinone β-D-glucopyranoside, is a naturally occurring antioxidant and skin brightener that is naturally found in the bearberry plant.

Alpha-Arbutin reduces melanin formation, improving the appearance of age spots, freckles, melasma, and post-inflammatory pigmentation.
Alpha-Arbutin is a glycosylated hydroquinone molecule, meaning a sugar molecule that has replaced one of the hydroxyl (-OH) groups on hydroquinone.

Hydroquinone is seen as the gold standard of skin lightening, but there are concerns surrounding this well-studied tyrosinase inhibitor, such as skin sensitization, melanocytotoxicity from oxidative byproducts, and exogenous ochronosis (blue-black splotchy pigmentation) as a result of long-term application.

Alpha-Arbutin is a more tolerable alternative to hydroquinone and is sometimes referred to as “natural hydroquinone.”
Alpha-Arbutin functions similarly to hydroquinone, due to its molecular structure, but with reduced irritation and melanocytotoxicity.

Alpha-Arbutin does not pose a risk in regards to exogenous ochronosis and poses minimal irritation and sensitization risk, making it a more tolerable alternative to hydroquinone.
Alpha-Arbutin is the α-anomer of arbutin (a glycosylated hydroquinone).

Alpha-Arbutin is a glucose (glycoside) derivative of hydroquinone used primarily as a topical skin-brightening / depigmenting active.
Alpha-arbutin (CAS 84380-01-8) is a water-soluble glycoside of hydroquinone used as a gentle, effective skin brightener that inhibits tyrosinase.

USES and APPLICATIONS of ALPHA-ARBUTIN:
Cosmetic uses of Alpha-Arbutin: brightening serums, anti-pigmentation creams, spot treatments, products for melasma, solar lentigo (age spots), post-inflammatory hyperpigmentation.
Typical commercial concentrations of Alpha-Arbutin: commonly 1–2% in facial products (EU SCCS refers to up to 2% for facial creams; lower levels for body).

Alpha-Arbutin is used in the cosmetic and pharmaceutical industries for its skin lightening effects, treatment of hyperpigmentation, and as a possibly safer alternative to hydroquinone.
Alpha-Arbutin may also possess antioxidant properties, which can protect the skin from free radical damage.

Alpha-Arbutin is used in the cosmetic and pharmaceutical industries for its skin lightening effects, treatment of hyperpigmentation, and as a safer alternative to hydroquinone.
Alpha-Arbutin is used in products aimed at fading solar lentigo, freckles, melasma, and other forms of hyperpigmentation where excess melanin is a concern, providing a more even skin complexion.

For this purpose, concentrations of up to 2% Alpha-Arbutin are found in face creams and serums and 0.5% in body creams.
Alpha-Arbutin showed a significant reduction in melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model, with melanin synthesis reduced to 40% of the control, indicating its potency as a skin lightening agent without affecting cell viability.

Alpha-Arbutin is a glucose (glycoside) derivative of hydroquinone used primarily as a topical skin-brightening / depigmenting active.
Alpha-Arbutin inhibits tyrosinase (the key enzyme in melanin synthesis) and is used to treat hyperpigmentation (age spots, melasma, post-inflammatory hyperpigmentation, freckles).

Alpha-arbutin is commonly used in cosmetic serums and creams because it is more stable and often reported as more potent than β-arbutin.
UV detection: λmax near ~280 nm helps in HPLC/UV methods.

Databases and publications show analytical methods for measuring Alpha-Arbutin and detecting hydroquinone impurities.
Alpha-Arbutin is widely used at ~1–2% in facial serums/creams; the EU SCCS has evaluated its safety and emphasizes impurity control (hydroquinone) and sets guidance around usage concentrations.

BENEFITS of ALPHA-ARBUTIN:
Alpha-Arbutin is gradual, gentle lightening of hyperpigmented areas; generally well tolerated; 
Alpha-Arbutin is less irritating than hydroquinone; 
Alpha-Arbutin is compatible with many water-based formulations (because Alpha-Arbutin is water-soluble).

COSMETIC CHARACTERISTICS of ALPHA-ARBUTIN:
Alpha-Arbutin is water-soluble active, blends into serums and creams, often combined with other actives (niacinamide, vitamin C, AHAs, tranexamic acid) for synergistic brightening effects.

FORMULATION & STABILITY NOTES of ALPHA-ARBUTIN:
Alpha-arbutin is water-soluble and usually incorporated into the aqueous phase of emulsions or into hydrating serums.
Alpha-Arbutin is typically stable under normal cosmetic formulation/storage when hydroquinone contamination is controlled; heat or acidic conditions could affect stability/de-glycosylation in extreme conditions (formulators prefer pH and process ranges that maintain glycoside stability).

MECHANISM OF ACTION (HOW IT WORKS) of ALPHA-ARBUTIN:
Alpha-arbutin acts primarily by competitive inhibition of tyrosinase activity in melanocytes, reducing conversion steps that lead to melanin production and thus decreasing pigmentation over time.
Laboratory models (cell cultures and 3-D skin models) show substantial reduction in melanin synthesis after treatment with Alpha-Arbutin.

WHAT DOES ALPHA-ARBUTIN DO?
Alpha-Arbutin acts as a tyrosinase competitive inhibitor and also slows melanosome maturation (the organelles that synthesize and store melanin or pigment).
This is significant because Alpha-Arbutin works on two different mechanisms of pigmentation.

Melanin is derived from the amino acid tyrosine and this conversion is regulated by the enzyme tyrosinase.
Alpha-Arbutin is similar in structure to tyrosine, which fits into tyrosinase, needed for melanogenesis.

This means that Alpha-Arbutin is reversibly competing with tyrosine for a spot on the enzyme and not inhibiting cell viability, so therefore is not cytotoxic.

By targeting tyrosinase, the rate-limiting enzyme in melanin formation, as well as slowing production of the organelles that produce melanin, Alpha-Arbutin is a potent skin brightening agent.

WHAT ARE THE BENEFITS OF ALPHA-ARBUTIN?
Alpha-Arbutin effectively lightens and reduces UV induced pigmentation and free radicals, without increasing sun sensitivity.
Alpha-Arbutin fades discoloration caused by inflammation and environmental stressors while evening skin tone.
Alpha-Arbutin also addresses glycation, sugar-induced skin sallowness and loss of elasticity.

PROPERTIES AND SYNTHESIS of ALPHA-ARBUTIN:
Alpha-Arbutin is a synthetic substance that can be produced by enzymatic glycosylation of hydroquinone in the presence of α-amylase and dextrin.
In one example, this has been done in recombinant Escherichia coli, using amylase of Bacillus subtilis and sucrose phosphorylase of Leuconostoc mesenteroides.
Structurally, Alpha-Arbutin is the α-anomer of arbutin (β-arbutin), and like the β-form it is an enzyme inhibitor of human tyrosinase.

HOW ALPHA-ARBUTIN WORKS
Alpha-arbutin is a choice brightening ingredient because it's a derivative of hydroquinone, one of the most effective skin-lightening and spot-fading actives out there.
But while hydroquinone is a champ at gradually fading dark spots, Alpha-Arbutin has a safety profile that's a little, well, questionable.

Alpha-Arbutin works by slowly releasing hydroquinone over time, inhibiting tyrosinase, the key enzyme responsible for the production of melanin, or pigment, in the skin.

In other words, less tyrosinase means less pigment, which means less discoloration and fewer unwanted dark spots.
Alpha-arbutin is also known to have antioxidant and anti-inflammatory properties, she adds.

MECHANISM OF ACTION of ALPHA-ARBUTIN:
Alpha-Arbutin's mechanism of action as a skin lightening agent is primarily through the competitive enzymatic inhibition of tyrosinase, leading to a decrease in melanin production without affecting the mRNA gene expression of tyrosinase.

Alpha-Arbutin is more potent an inhibitor of tyrosinase than arbutin.
Alpha-Arbutin directly inhibits the enzymatic activity of tyrosinase, which is essential for melanin synthesis.

Tyrosinase catalyzes the first two steps in melanin production: the hydroxylation of tyrosine to l-DOPA and the oxidation of l-DOPA to dopaquinone.
By inhibiting tyrosinase, Alpha-Arbutin reduces the formation of melanin in melanocytes.

Alpha-Arbutin does not affect the gene expression of tyrosinase mRNA.
This means that while Alpha-Arbutin inhibits the activity of the tyrosinase enzyme, it does not decrease the enzyme's production at the genetic level.

This reduction in melanin leads to lighter skin tones and can help in the treatment of hyperpigmentation disorders.
The efficacy of Alpha-Arbutin in reducing melanin synthesis was demonstrated in cultured human melanoma cells and a three-dimensional human skin model, where it effectively reduced melanin synthesis.

PHYSICAL and CHEMICAL PROPERTIES of ALPHA-ARBUTIN:
Molecular Weight: 272.25 g/mol
XLogP3: -0.7
Hydrogen Bond Donor Count: 5
Hydrogen Bond Acceptor Count: 7
Rotatable Bond Count: 3
Exact Mass: 272.08960285 g/mol
Monoisotopic Mass: 272.08960285 g/mol
Topological Polar Surface Area: 120Ų
Heavy Atom Count: 19
Formal Charge: 0
Complexity: 279

Isotope Atom Count: 0
Defined Atom Stereocenter Count: 5
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes
INCI / common name: Alpha-Arbutin (α-Arbutin). 
IUPAC / systematic name: 4-Hydroxyphenyl-α-D-glucopyranoside (sometimes written Hydroquinone-α-glucopyranoside). 

CAS number: 84380-01-8. 
EC / EINECS numbers (as reported in SCCS / EU docs): 
EC: 617-561-8; 
EINECS/ELINCS: 440-470-8. (SCCS / EU opinion lists these identifiers.) 
PubChem CID: 158637
Molecular formula: C₁₂H₁₆O₇. 
Molar mass (molecular weight): ≈ 272.25 g·mol⁻¹. 
Structure / SMILES / InChIKey: see PubChem / ChemSpider for structure images and exact InChI/SMILES (InChIKey: BJRNKVDFDLYUGJ-ZIQFBCGOSA-N). 

Appearance: white to off-white crystalline powder (common description in supplier datasheets). 
Solubility: water-soluble (reports vary; sources list high water solubility — examples: ~151 g/L reported on some pages). 
Soluble in aqueous systems used in cosmetic formulations. 
Melting point: reported around ~201 °C (literature / database values vary slightly by source). 
Boiling / decomposition: not typically relevant for cosmetic use; decomposition reported at high temperatures (databases list high boiling/decomp values). 
UV absorbance (λmax): around ~280 nm (useful in analytical characterization). 
Physical state for handling: solid powder

FIRST AID MEASURES of ALPHA-ARBUTIN:
-Description of first-aid measures:
*General advice:
Show this material safety data sheet to the doctor in attendance.
*If inhaled:
After inhalation: 
Fresh air. 
Call in physician.
*In case of skin contact: 
Take off immediately all contaminated clothing. 
Rinse skin with water/ shower. 
Consult a physician.
*In case of eye contact:
After eye contact: 
Rinse out with plenty of water. 
Immediately call in ophthalmologist.
Remove contact lenses.
*If swallowed:
After swallowing: 
Immediately make victim drink water (two glasses at most). 
Consult a physician.
-Indication of any immediate medical attention and special treatment needed:
No data available

ACCIDENTAL RELEASE MEASURES of ALPHA-ARBUTIN:
-Environmental precautions:
Do not let product enter drains.
-Methods and materials for containment and cleaning up:
Cover drains. 
Collect, bind, and pump off spills. 
Observe possible material restrictions.
Take up dry. 
Dispose of properly. 
Clean up affected area.

FIRE FIGHTING MEASURES of ALPHA-ARBUTIN:
-Extinguishing media:
*Suitable extinguishing media:
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
-Further information:
Prevent fire extinguishing water from contaminating surface water or the ground water system.

EXPOSURE CONTROLS/PERSONAL PROTECTION of ALPHA-ARBUTIN:
-Exposure controls:
--Personal protective equipment:
*Eye/face protection:
Use equipment for eye protection.
Tightly fitting safety goggles
*Skin protection:
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: 480 min
Splash contact:
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: 480 min
*Body Protection:
protective clothing
-Control of environmental exposure:
Do not let product enter drains.

HANDLING and STORAGE of ALPHA-ARBUTIN:
-Conditions for safe storage, including any incompatibilities:
*Storage conditions:
Tightly closed. 
Dry.
Store at Room Temperature. 
Light sensitive

STABILITY and REACTIVITY of ALPHA-ARBUTIN:
-Chemical stability:
The product is chemically stable under standard ambient conditions (room temperature) .
-Incompatible materials:
No data available