The vitality of B16 melanoma cells is inhibited by arbutin (0.3-5.4 mM; 24 hours, 48 hours, 72 hours; B16 melanoma cells) in a dose- and time-dependent way [2].

Arbutin (50 mg/kg, 100 mg/kg; side wall; daily; 17 days; model C57BL/6 model) simulates ventricular hypertrophy generated by ISO and has a substantial protective effect [3].

Cell Viability Assay[2]
Cell Types: B16 murine melanoma cells
Tested Concentrations: 0.3 mM, 0.7 mM, 1.4 mM, 2.1 mM 24 hrs (hours)) The sterilization rate of B16 murine melanoma cells treated with a dose of 5.4 mM[2]. , 2.9 mM, 3.6 mM, 5.4 mM
Incubation Duration: 24 hrs (hours), 48 hrs (hours) or 72 hrs (hours)
Experimental Results: Inhibited the viability of B16 mouse melanoma cells in a time- and dose-dependent manner.

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Apoptosis analysis [2]
Cell Types: B16 mouse melanoma cells
Tested Concentrations: 1.4 mM, 2.9 mM, 5.4 mM
Incubation Duration: 24 hrs (hours)
Experimental Results: Caused 19.3% of cell apoptosis.

Animal/Disease Models: Male C57BL/6 mice (20-25g) [3]
Doses: 50mg/kg, 100mg/kg
Route of Administration: Oral; daily; 17 days
Experimental Results: Improved myocardial damage caused by ISO.

Absorption, Distribution and Excretion
Arbutin is widely absorbed in the gastrointestinal tract and is primarily converted to hydroquinone. Within 4 hours of a single 210 mg dose of arbutin in healthy volunteers, 224.5 μmol/L hydroquinone glucuronide and 182 μmol/L hydroquinone sulfate were detected in the urine. No pharmacokinetic data are available. A randomized crossover design was used to investigate the urinary excretion of arbutin metabolites in 16 healthy volunteers following a single oral administration of arbutin leaf dry extract (BLDE). Subjects were divided into two groups, receiving either film-coated tablets (FCT) or aqueous solution (AS). Urine samples were analyzed using validated high-performance liquid chromatography-cold array (hydroquinone) and validated capillary electrophoresis (hydroquinone-glucuronide, hydroquinone-sulfate). The total amount of hydroquinone equivalent excreted in the urine was similar between the two groups. Subjects in the FCT group excreted 64.8% of the arbutin dose; subjects in the AS group excreted 66.7% (p = 0.61). The maximum mean concentration of hydroquinone equivalent in urine was slightly higher in the AS group than in the FCT group, and the peak time was earlier, but the difference was not statistically significant (Cur max = 1.6893 μmol/mL vs. 1.1250 μmol/mL, p = 0.13; tmax (midpoint) = 3.60 h vs. 4.40 h, p = 0.38). Compared with AS, the relative bioavailability of total hydroquinone equivalent in FCT was 103.3%. Individual differences were significant. There were no significant differences in the detected metabolite patterns (hydroquinone, hydroquinone-glucuronide, and hydroquinone-sulfate) between the two groups. This study aimed to investigate the effects of aloin and arbutin on normally cultured human melanocytes using a synergistic approach. A human melanocyte culture system was constructed. Cultured melanocytes were treated with a mixture of aloin and arbutin. Cell viability and tyrosinase activity were determined using the MTT assay and levodopa-based tyrosinase activity assay, respectively; melanin content was determined using an image analysis system. Furthermore, the effects of the mixture versus aloin and arbutin on melanocytes were compared. The mixture of aloin and arbutin inhibited tyrosinase activity in human melanocytes and significantly reduced melanin content. The difference between the mixture and aloin or arbutin alone was significant (P<0.05). On the other hand, the mixture had little effect on melanocyte viability and showed a negative correlation. The mixture of aloin and arbutin significantly inhibited tyrosinase activity and melanin production in cultured human melanocytes, indicating a synergistic effect between aloin and arbutin.

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Metabolism/Metabolites
Arbutin is readily hydrolyzed in dilute acid to form D-glucose and hydroquinone. It is expected that orally administered arbutin will be readily hydrolyzed into free hydroquinone molecules under the action of gastric acid. Hydroquinone is further metabolized into its major metabolites, hydroquinone glucuronide and hydroquinone sulfate.

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Biological half-life
No pharmacokinetic data available.

Protein Binding

No pharmacokinetic data available.

[1]. Action of tyrosinase on alpha and beta-arbutin: A kinetic study. PLoS One. 2017 May 11;12(5):e0177330.

[2]. Investigation of the pro-apoptotic effects of arbutin and its acetylated derivative on murinemelanoma cells. Int J Mol Med. 2018 Feb;41(2):1048-1054.

[3]. Arbutin Attenuates Isoproterenol-Induced Cardiac Hypertrophy by Inhibiting TLR-4/NF-κB Pathway in Mice. Cardiovasc Toxicol. 2019 Sep 4.

Hydroquinone O-β-D-glucopyranoside is a monosaccharide derivative consisting of hydroquinone linked to a β-D-glucopyranose residue at position 4 via a glycosidic bond. It is both a plant metabolite and an Escherichia coli metabolite. It is a β-D-glucopyranoside and a monosaccharide derivative. Its function is related to hydroquinone. Arbutin is extracted from the dried leaves of plants in the genus Arctostaphylos and other common plants in the Ericaceae family; it is the β-D-glucopyranoside of [DB09526]. It is found in food, over-the-counter drugs, and herbal dietary supplements. Its most common use is as an active ingredient in skincare and cosmetic products, used as a skin whitening agent to prevent melanin formation in various skin conditions, including hyperpigmentation or melanocyte hyperfunction. It has also been used as an anti-infective agent for the urinary system and as a diuretic. Arbutin exists in both natural and synthetic forms; it can be synthesized from acetylglucosamine and [DB09526]. Arbutin is a competitive inhibitor of tyrosinase (EC 1.14.18.1) in melanocytes, and in vitro experiments have shown that it inhibits melanin synthesis at non-toxic concentrations. Compared with [DB09526], arbutin exhibits lower cytotoxicity to cultured melanocytes. Arbutin has been reported to be found in tea tree (Camellia sinensis), myrothamnus flabellifolia, and several other organisms with relevant data. See also: Arbutin leaf (part); Arbutin; Octyl methoxycinnamate (ingredient); Adenosine; Arbutin (ingredient)... See more...

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Drug Indications
For over-the-counter treatment of epidermal hyperpigmentation caused by various skin conditions, such as melasma, freckles, and age spots.

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Mechanism of Action
Arbutin is a hydroquinone glycoside, but the hydroquinone moiety is not the sole reason for its depigmenting effect. Arbutin exerts its depigmenting effect on human skin by acting on the L-tyrosine binding site, acting as a competitive inhibitor of tyrosinase, thereby inhibiting melanin production. Tyrosinase is an enzyme involved in regulating the rate-limiting step of melanin synthesis; it regulates the conversion of L-tyrosine to L-DOPA, and the further conversion of L-DOPA to L-DOPAquinone. Arbutin reduces melanin production in melanocytes by inhibiting tyrosinase activity in a concentration-dependent manner. Although most studies have shown that arbutin has a negligible effect on tyrosinase mRNA expression, a study using embryonic stem cells to assess the effect of arbutin on the melanocyte differentiation-inducing system suggests that arbutin may downregulate tyrosinase expression in addition to inhibiting tyrosinase activity. The conflicting results may be due to the use of terminally differentiated melanocytes and melanoma cells in previous studies. This study… provides evidence that the combined use of aloin and arbutin can synergistically inhibit tyrosinase activity through different mechanisms of action. Aloe vera and arbutin exhibited similar inhibitory effects on human and mushroom-derived tyrosinases, with IC50 values of 0.1 mM and 0.04 mM, respectively. Lineweaver-Burk plotting of enzyme kinetic data showed that aloin inhibited tyrosinase activity non-competitively (Ki value 5.3 mM), while arbutin inhibited it competitively (Maeda, 1996). We then investigated whether combined treatment with these two substances synergistically inhibited tyrosinase activity. The results showed that in the presence of 0.03 mM arbutin, 0.01 mM aloin inhibited mushroom tyrosinase activity to 80% of the control group, and vice versa. Calculations using the Burgi method indicated a synergistic inhibitory effect. In conclusion, we believe that aloin and arbutin synergistically inhibit melanin production through a combined mechanism of non-competitive and competitive inhibition of tyrosinase activity.

C12H16O7

272.2512

272.089

497-76-7

Arbutin-d4

440936

White to off-white solid powder

1.6±0.1 g/cm3

561.6±50.0 °C at 760 mmHg

195-198 °C

293.4±30.1 °C

0.0±1.6 mmHg at 25°C

1.650

-1.35

5

7

3

19

279

5

C1=CC(=CC=C1O)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O

BJRNKVDFDLYUGJ-RMPHRYRLSA-N

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

(2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-(4-hydroxyphenoxy)oxane-3,4,5-triol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~183.65 mM)
H2O : ~33.33 mg/mL (~122.42 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (367.31 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)