Identification

Name
Arbutin
Accession Number
DB11217
Type
Small Molecule
Groups
Approved
Description

Extracted from the dried leaves of bearberry plant in the genus Arctostaphylos and other plants commonly in the Ericaceae family, arbutin is a beta-D-glucopyranoside of Hydroquinone. It is found in foods, over-the-counter drugs, and herbal dietary supplements [6]. Most commonly, it is an active ingredient in skincare and cosmetic products as a skin-lightening agent for the prevention of melanin formation in various skin conditions that involve cutaneous hyperpigmentation or hyperactive melanocyte function [1]. It has also been used as an anti-infective for the urinary system as well as a diuretic [6]. Arbutin is available in both natural and synthetic forms; it can be synthesized from acetobromglucose and Hydroquinone [6]. Arbutin is a competitive inhibitor of tyrosinase (E.C.1.14.18.1) in melanocytes [1], and the inhibition of melanin synthesis at non-toxic concentrations was observed in vitro. Arbutin was shown to be less cytotoxic to melanocytes in culture compared to Hydroquinone [5].

Structure
Thumb
Synonyms
  • 4-Hydroxyphenyl-beta-D-glucopyranoside
  • beta-Arbutin
  • hydroquinone O-β-D-glucopyranoside
  • Hydroquinone-O-beta-D-glucopyranoside
  • p-hydroxyphenyl β-D-glucopyranoside
  • p-hydroxyphenyl β-D-glucoside
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AHC Phyto Complex Gel AmpouleLiquid0.6 g/30mLTopicalCarver Korea Co.,Ltd.2013-08-15Not applicableUs
Dr Young 2p Brightening UV Sun Block SPF50 PACream0.5 mL/50mLTopicalThe Doctor's Cosmetic Inc2009-11-01Not applicableUs
Elcure C White SerumLiquid2 g/100mLTopicalElcure Co., Ltd.2016-03-302017-04-20Us
Hydro HSolution2.5 mg/1mLTopicalGeneral Bio Co., Ltd.2014-12-09Not applicableUs
IASO White Science EXCream0.02 g/1gTopicalIaso Inc2011-01-172018-03-12Us
IASO White Science EX EmulsionCream0.02 g/1mLTopicalIaso Inc2011-01-172018-03-12Us
Isaknox White Symphony Brightening EmulsionLotion2.1 g/100gTopicalLg Household & Health Care Ltd.2010-03-29Not applicableUs
ObagiCream4.03 mg/57gTopicalYS PLUS CORPORATION2014-10-012015-12-31Us
Obagi Nu-Derm Clear FxCream4.02 mg/57gTopicalYS PLUS CORPORATION2014-10-012015-12-31Us
Sooryehan Pure WhiteningEmulsion2.1 mL/100mLTopicalLg Household & Health Care Ltd.2010-05-142011-05-14Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Abalone Crystaldouble EX AmpouleArbutin (2.2 g/100mL) + Adenosine (0.044 g/100mL)LiquidTopicalC&bcosmetic Co.,ltd.2017-03-10Not applicableUs
Absolute Total BB SPF37 PA 3PlusArbutin (0.8 g/40g) + Adenosine (0.016 g/40g) + Titanium dioxide (3.6 g/40g) + Zinc oxide (2.52 g/40g)CreamTopicalWizcoz Corporation Ltd2011-12-01Not applicableUs
AHC Premium Intense Contour BalmArbutin (1 g/50mL) + Adenosine (0.02 g/50mL) + Aluminium tristearate (0.04 g/50mL) + Aluminum hydroxide (0.45 g/50mL) + Methicone (20 cst) (1.3 g/50mL) + Octinoxate (1.5 g/50mL) + Talc (2.05 g/50mL) + Titanium dioxide (3.96 g/50mL) + Zinc oxide (0.96 g/50mL)CreamTopicalCarver Korea Co.,Ltd.2014-01-152017-11-22Us
AHC Vital Complex C-15 AmpouleArbutin (0.6 g/30mL) + Adenosine (12 mg/30mL)LiquidTopicalCarver Korea Co.,Ltd.2013-08-15Not applicableUs
Cathycat Chewy CREAM FOUNDATION SPF23 PA WHITENING ANTI WRINKLE 21Arbutin (2 g/100g) + Hydroxyproline (0.5 g/100g) + Octinoxate (1.5 g/100g) + Titanium dioxide (8.2062 g/100g)LiquidTopicalLg Household & Health Care Ltd.2011-04-152012-04-15Us
Cathycat Chewy CREAM FOUNDATION SPF23 PA WHITENING ANTI WRINKLE 23Arbutin (2 g/100g) + Hydroxyproline (0.5 g/100g) + Octinoxate (1.5 g/100g) + Titanium dioxide (8.2062 g/100g)LiquidTopicalLg Household & Health Care Ltd.2011-04-152012-04-15Us
Cellbn Damage Anti-aging Eye ReviverArbutin (2 g/100mL) + Adenosine (0.05 g/100mL)CreamTopicalWorldcostec.co.,ltd2017-05-26Not applicableUs
Cellbn Damage Deep MoistureArbutin (2 g/100mL) + Adenosine (0.05 g/100mL)CreamTopicalWorldcostec.co.,ltd2017-05-26Not applicableUs
Cellbn Damage Multi Action TonerArbutin (1 g/100mL) + Adenosine (0.05 g/100mL)LiquidTopicalWorldcostec.co.,ltd2017-05-26Not applicableUs
Cellbn Damage Overnight RecoveryArbutin (2 g/100mL) + Adenosine (0.05 g/100mL)CreamTopicalWorldcostec.co.,ltd2017-05-26Not applicableUs
International/Other Brands
Ursin / Uvasol
Categories
UNII
C5INA23HXF
CAS number
497-76-7
Weight
Average: 272.2512
Monoisotopic: 272.089602866
Chemical Formula
C12H16O7
InChI Key
BJRNKVDFDLYUGJ-RMPHRYRLSA-N
InChI
InChI=1S/C12H16O7/c13-5-8-9(15)10(16)11(17)12(19-8)18-7-3-1-6(14)2-4-7/h1-4,8-17H,5H2/t8-,9-,10+,11-,12-/m1/s1
IUPAC Name
(2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-(4-hydroxyphenoxy)oxane-3,4,5-triol
SMILES
OC[C@H]1O[C@@H](OC2=CC=C(O)C=C2)[C@H](O)[C@@H](O)[C@@H]1O

Pharmacology

Indication

Indicated for over-the-counter use for epidermal hyperpigmentation in various skin conditions, such as melasma, freckles, and senile lentigines.

Pharmacodynamics

At non-toxic concentrations, arbutin inhibited the activity of tyrosinase in cultured human keratinocytes, while having minimal effect on the expression of tyrosinase mRNA or the synthesis of the enzyme [1]. α-Arbutin produced a concentration-dependent inhibition of melanin synthesis of human melanoma cells, HMV-II [3]. No inhibitory effect on HMV-II cell growth was seen at concentrations lower than 1.0 mM. At concentrations of 0.5 mM of arbutin, tyrosinase activity was reduced to 60% of that in non-treated cells [3]. The addition of arbutin blocked and inhibited α-MSH-stimulated melanogenesis in B16 melanoma cells, brownish guinea pig, and human skin tissue [4]. In a pilot study of healthy male adults exposed to UV B irradiation, topical administration of arbutin inhibited UV-induced nuclear factor-kappaB activation in human keratinocytes [6]. In mouse skin, arbutin counteracted oxidative stress induced by 12-O-tetradecanoylphorbol-13-acetate [6].

Mechanism of action

Arbutin is a hydroquinone glycoside, however the hydroquinone moiety is not solely responsible for the de-pigmentating actions of arbutin [5]. It acts as a competitive inhibitor of tyrosinase enzyme by acting on the L-tyrosine binding site to suppress melanogenesis and mediate its de-pigmenting actions on human skin [1]. Tyrosinase is an enzyme involved in the regulation of rate-limiting steps during the synthesis of melanin; it regulates the conversion of L-tyrosine into L-dopa, and subsequent conversion of L-dopa to L-dopaquinone [1]. Via inhibition of tyrosinase activity in a concentration-dependent manner, arbutin attenuates the production of melanin in melanocytes. While most studies suggest that arbutin has negligible effect on the tyrosinase mRNA expression, a study assessing the effect of arbutin on melanocyte differentiation inducement system using ES cells propose that arbutin may also downregulate the expression of tyrosinase in addition to its inhibitory action on the enzyme [2]. The contradictory findings across studies may be due to previous studies using terminally-differentiated melanocytes and melanoma cells [2].

TargetActionsOrganism
ATyrosinase
inhibitor
Human
Absorption

Arbutin was found to be extensively absorbed from the gastrointestinal tract where it is primarily converted to hydroquinone [6].

Volume of distribution

No pharmacokinetic data available.

Protein binding

No pharmacokinetic data available.

Metabolism

Arbutin is readily susceptible to hydrolysis in dilute acids to yield D-glucose and hydroquinone. It is expected that orally administered arbutin is easily hydrolyzed to free hydroquinone molecules by stomach acid [6]. Hydroquinone is further metabolized into the main metabolites, hydroquinone glucuronide and hydroquinone sulfate [6].

Route of elimination

During the first 4 hours following ingestion of a single dose of 210 mg arbutin in healthy volunteers, 224.5 μmol/L hydroquinone glucuronide and 182 μmol/L of hydroquinone sulfate were recovered in the urine [6].

Half life

No pharmacokinetic data available.

Clearance

No pharmacokinetic data available.

Toxicity

In an acute oral toxicity study, the LD50-value for β-arbutin is 9804 mg/kg bw for the mouse and 8715 mg/kg bw for the rat [7]. Dermal LD50 value in rat and mouse was reported to be greater than 928 mg/kg bw, according to an acute dermal toxicity study [7]. Extremely high doses may cause ringing in the ears, shortness of breath, convulsions, collapse, vomiting and delirium [6]. Nausea and vomiting were seen individuals with sensitive stomachs following oral ingestion of 15 g of dried uva ursi leaves that contain arbutin [6].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Maeda K, Fukuda M: Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther. 1996 Feb;276(2):765-9. [PubMed:8632348]
  2. Inoue Y, Hasegawa S, Yamada T, Date Y, Mizutani H, Nakata S, Matsunaga K, Akamatsu H: Analysis of the effects of hydroquinone and arbutin on the differentiation of melanocytes. Biol Pharm Bull. 2013;36(11):1722-30. [PubMed:24189417]
  3. Sugimoto K, Nishimura T, Nomura K, Sugimoto K, Kuriki T: Inhibitory effects of alpha-arbutin on melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model. Biol Pharm Bull. 2004 Apr;27(4):510-4. [PubMed:15056856]
  4. Lim YJ, Lee EH, Kang TH, Ha SK, Oh MS, Kim SM, Yoon TJ, Kang C, Park JH, Kim SY: Inhibitory effects of arbutin on melanin biosynthesis of alpha-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues. Arch Pharm Res. 2009 Mar;32(3):367-73. doi: 10.1007/s12272-009-1309-8. Epub 2009 Apr 23. [PubMed:19387580]
  5. Chakraborty AK, Funasaka Y, Komoto M, Ichihashi M: Effect of arbutin on melanogenic proteins in human melanocytes. Pigment Cell Res. 1998 Aug;11(4):206-12. [PubMed:9711535]
  6. Chemical Information Review Document for Arbutin [CAS No. 497-76-7] for Arbutin and Extracts from Arctostaphylos uva-ursi [File]
  7. European Commission Scientific Committee on Consumer Products (SCCP): Opinion on beta-arbutin [File]
External Links
KEGG Compound
C06186
PubChem Compound
440936
PubChem Substance
347827943
ChemSpider
389765
BindingDB
50219502
ChEBI
18305
ChEMBL
CHEMBL232202
Wikipedia
Arbutin
MSDS
Download (47.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3SuspendedTreatmentMelasma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidTopical0.6 g/30mL
GelTopical
CreamTopical
CreamTopical0.5 mL/50mL
LiquidTopical2 g/100mL
SolutionTopical2.5 mg/1mL
CreamTopical0.02 g/1g
CreamTopical0.02 g/1mL
LotionTopical2.1 g/100g
Aerosol, sprayTopical
CreamTopical4.03 mg/57g
CreamTopical4.02 mg/57g
PowderTopical
SprayTopical
EmulsionTopical2.1 mL/100mL
CreamTopical2.1 mL/100mL
LiquidTopical
EmulsionTopical
LiquidTopical1 mg/150mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)197MSDS
water solubility≥ 10g/100gEuropean Commission Scientific Committee on Consumer Products (SCCP): Opinion on beta-arbutin
logP1.35European Commission Scientific Committee on Consumer Products (SCCP): Opinion on beta-arbutin
Predicted Properties
PropertyValueSource
Water Solubility39.1 mg/mLALOGPS
logP-1.4ALOGPS
logP-0.9ChemAxon
logS-0.84ALOGPS
pKa (Strongest Acidic)9.82ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area119.61 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity62.16 m3·mol-1ChemAxon
Polarizability25.88 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (5 TMS)GC-MSsplash10-0uxr-1971000000-e8260464bad4d4a7fa0c
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0uxs-0940000000-9984522469f86670798f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - DI-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0229-0920000000-532b692f9942a62cc7c8
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0229-0910000000-1cb0580496288b7004fc
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-001i-0950000000-4bafd0325d0163331c0a
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-001i-0950000000-ffffdfe1cd448f0ea135
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-016r-0290000000-0ebc801fded534434aa5
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-016r-0390000000-5831b5a141106482d24d

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenolic glycosides. These are organic compounds containing a phenolic structure attached to a glycosyl moiety. Some examples of phenolic structures include lignans, and flavonoids. Among the sugar units found in natural glycosides are D-glucose, L-Fructose, and L rhamnose.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Phenolic glycosides
Alternative Parents
Hexoses / O-glycosyl compounds / 4-alkoxyphenols / Phenoxy compounds / Phenol ethers / 1-hydroxy-2-unsubstituted benzenoids / Oxanes / Secondary alcohols / Polyols / Oxacyclic compounds
show 3 more
Substituents
Phenolic glycoside / Hexose monosaccharide / O-glycosyl compound / 4-alkoxyphenol / Phenoxy compound / Phenol ether / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Monocyclic benzene moiety / Monosaccharide
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
beta-D-glucoside, monosaccharide derivative (CHEBI:18305)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein homodimerization activity
Specific Function
This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA ...
Gene Name
TYR
Uniprot ID
P14679
Uniprot Name
Tyrosinase
Molecular Weight
60392.69 Da
References
  1. Maeda K, Fukuda M: Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther. 1996 Feb;276(2):765-9. [PubMed:8632348]
  2. Chakraborty AK, Funasaka Y, Komoto M, Ichihashi M: Effect of arbutin on melanogenic proteins in human melanocytes. Pigment Cell Res. 1998 Aug;11(4):206-12. [PubMed:9711535]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Sakurai M, Ohsako M, Nagano M, Nakamura C, Tsuzuki O, Ichikawa M, Matsumoto Y: [Effect of human serum albumin on transport of drugs through human erythrocyte membranes]. Yakugaku Zasshi. 1996 Aug;116(8):630-8. [PubMed:8831264]

Drug created on December 03, 2015 09:51 / Updated on November 02, 2018 07:07