arbutin and Hyperpigmentation

Cosmetic dermatology preparations such as bleaching agents are ingredients with skin-related biological activities for increasing and improving skin beauty. The possibility of controlling skin hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. Recently, cosmetics containing herbal and botanical ingredients have attracted many interests for consumers of cosmetic products because these preparations are found safer than other preparations with synthetic components. However, high-quality trial studies in larger samples are needed to confirm safety and clinical efficacy of phytotherapeutic agents with high therapeutic index. Arbutin (p-hydroxyphenyl-β-d-glucopyranoside) is a bioactive hydrophilic polyphenol with two isomers including alpha-arbutin (4-hydroxyphenyl-α-glucopyranoside) and β-arbutin (4-hydroxyphenyl-β-glucopyranoside). It is used as a medicinal plant in phytopharmacy. Studies have shown that alpha-arbutin is 10 times more effective than natural arbutin. A comparison of IC50 values showed that α-arbutin (with concentration 2.0 mM) has a more potent inhibitory activity on human tyrosinase against natural arbutin (with higher concentration than 30 mM). A review of recent studies showed that arbutin could be beneficial in treatment of various diseases such as hyperpigmentation disorders, types of cancers, central nervous system disorders, osteoporosis, diabetes, etc. This study was designed to describe the therapeutic efficiencies of arbutin.

Topics: Arbutin; Cosmetics; Humans; Hyperpigmentation; Monophenol Monooxygenase; Skin

As Dermatologists caring for patients with hyperpigmentation problems, we are always looking for more alternative therapies. Hydroquinone (HQ) is still the standard of care. However, traditional depigmenting agents such as HQ and corticosteroids, although highly effective, can raise safety concerns including exogenous ochronosis, atrophy, carcinogenesis and local and systemic untoward effects with long term use. Therefore, we need to investigate non-prescription natural alternatives. This manuscript presents many of the natural ingredients found in cosmeceuticals for the treatment of hyperpigmentation and their mechanisms of action. It will also describe the melanocyte activation pathways and how each of these ingredients interferes with it.

Topics: Arbutin; Cosmeceuticals; Glycine max; Humans; Hydroquinones; Hyperpigmentation; Melanocytes; Plant Extracts; Vitamin A

Hyperpigmentation has traditionally been a relatively difficult condition to treat, especially in darker racial ethnic groups. Multiple topical agents available act upon different steps of the pigmentation pathway. We review these topical agents, their mechanisms of action, and their effectiveness as monotherapy and in combination with other compounds. Ultimately, combination therapy is the most efficacious when considering overall depigmentation as well as treatment time required to achieve clinical improvement.

Topics: Administration, Topical; Adrenal Cortex Hormones; Arbutin; Chromones; Drug Combinations; Free Radical Scavengers; Glucosides; Humans; Hydroquinones; Hyperpigmentation; Keratolytic Agents; Monophenol Monooxygenase; Niacinamide; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic; Receptor, PAR-2; Retinoids; Skin Diseases; Skin Lightening Preparations; Skin Pigmentation

Facial hyperpigmented disorders are a common complaint in the adult population of all races. First-line topical treatments are usually hydroquinone or topical retinoids, which can cause irritant reactions. The need for better tolerated, yet effective, skin lightening agents that could be utilized by a wider population has led to the investigation of several potential botanical/natural compounds. There are currently many topical cosmetic formulations claiming skin depigmenting effects. A few of the ingredients (e.g. soy) are supported not only by in vitro results but also by a body of controlled clinical efficacy studies; other ingredients, instead, are backed mostly by in vitro data and a few small uncontrolled clinical studies. In this review, we describe the most common natural ingredients used for skin depigmentation and their major published studies: soy, licorice extracts, kojic acid, arbutin, niacinamide, N-acetylglucosamine, COFFEEBERRY(™) and green tea.

Topics: Administration, Topical; Arbutin; Cosmetics; Glycyrrhiza; Humans; Hyperpigmentation; Plant Extracts; Pyrones; Soybean Proteins

Many skin lightening preparations containing hydroquinone, kojic acid, arbutin, and deoxyarbutin are toxic to melanocytes.. This research examined a new skin lightening agent from a family of gem difluorocompounds 2-[2-(2,4-difluorophenyl)-2-propen-1-yl]-1,3-propanediol that also function as tyrosinase inhibitors. This ingredient does not exhibit melanocyte toxicity yet is capable of inducing skin lightening. This research compared the gem difluorocompound, TFC-1067, to hydroquinone evaluating both tolerability and efficacy for lightening facial dyschromia.. 48 nonpregnant and non-nursing healthy female subjects age 25-70 years skin types I-IV with mild-to-moderate facial dyschromia were randomized to receive either study product or 2% hydroquinone cream. Subject and investigator tolerability and efficacy assessments were made at baseline, week 4, week 8, and week 12. Dermaspectrophotometer readings from normal skin and a pigmented target area were obtained. All subjects underwent facial photography at each visit.. TFC-1067 and 2% hydroquinone produced statistically significant skin lightening after 8 weeks of use, but only hydroquinone lightened the normal skin. This pattern continued into week 12 where both products significantly lightened dyschromic skin, but hydroquinone also lightened the normal skin, which is not always desirable.

Topics: Adult; Aged; Arbutin; Female; Humans; Hydroquinones; Hyperpigmentation; Middle Aged; Skin; Skin Lightening Preparations

Hyperpigmentary disorders like melasma, actinic and senile lentigines are a major cosmetic concern. Therefore, many topical products are available, containing various active ingredients aiming to reduce melanin production and distribution. The most prominent target for inhibitors of hyperpigmentation is tyrosinase, the key regulator of melanin production. Many inhibitors of tyrosinase are described in the literature; however, most of them lack clinical efficacy.. We were interested in evaluating the inhibition of skin pigmentation by well-known compounds with skin-whitening activity like hydroquinone, arbutin, kojic acid and 4-n-butylresorcinol. We compared the inhibition of human tyrosinase activity in a biochemical assay as well as inhibition of melanin production in MelanoDerm skin model culture. For some compounds, the in vivo efficacy was tested in clinical studies.. Arbutin and hydroquinone only weakly inhibit human tyrosinase with a half maximal inhibitory concentration (IC(50)) in the millimolar range. Kojic acid is 10 times more potent with an IC(50) of approximately 500 μmol/L. However, by far the most potent inhibitor of human tyrosinase is 4-n-butylresorcinol with an IC(50) of 21 μmol/L. In artificial skin models, arbutin was least active with an IC(50) for inhibition of melanin production > 5000 μmol/L. Kojic acid inhibited with an IC(50) > 400 μmol/L. Interestingly, hydroquinone inhibited melanin production in MelanoDerms with an IC(50) below 40 μmol/L, probably due to a mechanism different from tyrosinase inhibition. Again, 4-n-butylresorcinol was the most potent inhibitor with an IC(50) of 13.5 μmol/L. In vivo efficacy of 4-n-butyl-resorcinol was confirmed in clinical studies. Subjects with age spots on the forearm treated twice daily two age spots with a formula containing 4-n-butylresorcinol and two control age spots with the corresponding vehicle. Within 8 weeks, 4-n-butylresorcinol reduced visibly the appearance of age spots, while the control spots showed no improvement. A second study showed that 4-butylresorcinol was more effective than 4-hexylresorcinol and 4-phenylethylresorcinol.. The present in vitro and in vivo data prove the high inhibitory capacity of 4-n-butylresorcinol on human tyrosinase activity, exceeding by far the potency of hydroquinone, arbutin and kojic acid. The resulting clinical improvement of skin hyperpigmentations reveals 4-n-butylresorcinol as a very valuable active compound for the management of pigmentation disorders.

Topics: Administration, Topical; Aged; Arbutin; Female; Humans; Hydroquinones; Hyperpigmentation; Melanins; Middle Aged; Monophenol Monooxygenase; Pyrones; Resorcinols; Single-Blind Method; Skin; Skin Lightening Preparations; Tissue Culture Techniques; Treatment Outcome

Skin hyperpigmentation is caused by the overproduction of melanin pigment, which is synthesized by the action of tyrosinase. We recently reported that aloesin inhibits tyrosinase activity. The present study was undertaken to test the inhibitory effect of aloesin on pigmentation in human skin after UV radiation. Experimental subjects were UV-irradiated (210 mJ) on the inner forearm. UV-irradiated regions were assigned to four groups: vehicle control, aloesin treated, arbutin treated, and aloesin and arbutin treated. Aloesin and/or arbutin were administered four times a day for 15 days. Aloesin treatment suppressed pigmentation by 34%, arbutin by 43.5%, and the cotreatment by 63.3% compared with the control (n = 15; P < 0.05). Moreover, aloesin treatment showed pigmentation suppression in a dose-dependent manner (n = 7; P < 0.05). These results raise the possibility that aloesin may be used as an agent that inhibits melanin formation induced by UV radiation.

Topics: Adult; Analysis of Variance; Arbutin; Chromones; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glucosides; Humans; Hyperpigmentation; Male; Melanins; Radiation Injuries; Ultraviolet Rays

Excessive melanin formation has been linked to various skin disorders such as hyperpigmentation and skin cancer. Tyrosinase is the most prominent target for inhibitors of melanin production. In this study, we investigated whether arbutin and its prodrug, arbutin undecylenic acid ester, might inhibit phenoloxidase (PO), a tyrosinase-like enzyme. Molecular docking simulation results suggested that arbutin and arbutin undecylenic acid ester can bind to the substrate-binding pocket of PO. Arbutin undecylenic acid ester with an IC

Topics: Animals; Arbutin; Bombyx; Drosophila melanogaster; Hyperpigmentation; Melanins; Molecular Docking Simulation; Monophenol Monooxygenase; Undecylenic Acids

The present work designed to improve the skin delivery of arbutin niosome (arbusome) was prepared via an ultrasonic technique. The arbusome formulations were optimized by investigating the effects of the cholesterol:surfactants ratio. To characterize the morphology and solid-state of arbutin in arbusome, differential scanning calorimetry, photon correlation spectroscopy, powder x-ray diffractometer, scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared spectroscopy were utilized. The findings indicated that adding cholesterol incremented the arbusome's particle size. Further studies proved that the zeta potential and the size of nanoparticles can be modulated by the alterations in the ratio of cholesterol: surfactant. When the cholesterol concentration was high in the formulation, the highest entrapment efficiency was found to be approximately 44 %. Solid-state analysis showed that arbutin in the niosome was in the amorphous state. The skin permeation test indicated the greater quantities of the arbutin in skin layers and the receptor chamber for arbusome gel compared to arbutin simple gel. Furthermore, in vitro cytotoxicity test indicated no cytotoxicity for the improved formulation of niosome containing arbutin. The cell viability (HFF cell line) for niosomal formulation of arbutin was reported to be about 86 %. The formulations were examined in terms of skin irritation on Wistar rats, and non-irritancy of arbutin niosomal gels was indicated. The findings of this work discovered that the manufactured arbusome could be utilized as possible nano-vehicle for the arbutin topical delivery and might open new approaches for the treatment of hyperpigmentation complaints.

Topics: Animals; Arbutin; Hyperpigmentation; Lipids; Liposomes; Nanoparticles; Nanotechnology; Particle Size; Rats; Rats, Wistar; Skin

Hyperpigmentation can be either diffused or localized. In treating diffused hyperpigmentation, larger surface area coverage is the requirement. Novel user-friendly spray formulation loaded with depigmenting agents can cater the night time need in treating skin darkening. Kojic acid and arbutin, the selected actives for the study exhibit low permeability and high irritancy generating hurdles in topical delivery.. The aim of this study was to develop novel kojic acid and arbutin-loaded spray formulation as a night care product.. "Thermosensitive gel spray" was fabricated by simple industry feasible cooling technique and evaluated for its ability to improve skin retention, penetration, improved anti-tyrosinase activity, and suppressed dermal irritancy.. Comparative in-vitro and ex-vivo release profile showed the marked effect of poloxamer 407 and Methocel K100M in improving penetration and extending release over longer time period. Retention of actives in the skin layer was found to be eight times more in case of thermosensitive gel spray as compared to conventional gel formulation. The thermosensitive gel spray was free from any dermal irritancy and had higher tyrosinase inhibitory effect as against conventional gel. Furthermore, thermosensitive gel spray exhibited good stability and did not show any change in morphology and drug content during the 3-month storage.. Kojic acid and arbutin-loaded thermosensitive gel spray can prove to be a promising strategy to treat hyperpigmentation.

Topics: Animals; Arbutin; Chick Embryo; Chorioallantoic Membrane; Cosmeceuticals; Drug Compounding; Drug Liberation; Drug Stability; Gels; Hyperpigmentation; Monophenol Monooxygenase; Photoperiod; Pyrones; Skin; Skin Care; Toxicity Tests

We have previously found that mycelia culture broth of eight kinds of traditional herbal extracts fermented with

Topics: Animals; Arbutin; Basidiomycota; Epidermis; Fermented Foods; Guinea Pigs; Hyperpigmentation; Male; Melanins; Melanocytes; Models, Animal; Monophenol Monooxygenase; Phellinus; Plant Extracts; Skin; Skin Lightening Preparations; Skin Pigmentation; Ultraviolet Rays

Diverse compound sources are being explored for de-pigmentation activities to develop novel therapeutic agents or functional cosmetic ingredients for hyper-pigmentation disorders. Peptoids are a class of peptidomimetics whose side chains are appended to the nitrogen atom of the peptide backbone, instead of α-carbon. Peptoids are more durable against proteolysis and are being actively investigated in drug discovery, but rarely studied as cosmetic ingredients. Here, we demonstrated that new hexa-peptoids, PAL-10 and PAL-12, can inhibit melanogenesis in B16F10 melanoma cells, a 3D pigmented human skin model (Neoderm(®)-ME, Tegoscience Co) and zebrafish. Anti-melanogenic effects of PAL-10 or PAL-12 as compared with arbutin, a positive control in B16F10 cells, Neoderm(®)-ME and zebrafish were statistically significant and concentration-dependent anti-melanogenic effects were manifested as determined by image, histology, and melanin contents. Anti-melanogenic effects of PAL-10 appeared to be from enzymatic inhibition of tyrosinase while mRNA expression of melanogenic enzymes was not affected. In conclusion, we demonstrated that PAL-10 and PAL-12 can be used as a new cosmetic ingredient with strong brightening efficacies.

Topics: Animals; Arbutin; Cosmetics; Elastin; Humans; Hyperpigmentation; Melanins; Melanoma, Experimental; Mice; Monophenol Monooxygenase; Organ Culture Techniques; Peptoids; Protein Stability; Skin; Zebrafish

Hyperpigmentation disorders such as freckles and senile lentigines in the skin are associated with abnormal accumulation of melanin pigments. In this study, two lignan constituents were isolated from Saururus chinensis Baill (Saururaceae) as inhibitors of cellular melanin production by bioassay-guided fractionations. The active constituents were manassantin A and B that dose-dependently inhibited melanin production in alpha-melanocyte stimulating hormone (alpha-MSH)-activated melanoma B16 cells with IC(50) values of 13 nm and 8 nm, respectively. Arbutin as a positive control exhibited an IC(50) value of 96 microm on alpha-MSH-induced melanin production. Further, manassantin A inhibited forskolin- or 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production with IC(50) values of 14 nm or 12 nm, respectively. Manassantin A decreased cellular amounts of IBMX-inducible tyrosinase protein but could not affect the catalytic activity of cell-free tyrosinase, a key enzyme in the biosynthetic pathway of melanin pigments. Finally, this study could provide a pharmacological potential of S. chinensis in hyperpigmentation disorders.

Topics: Animals; Arbutin; Cell Line, Tumor; Furans; Hyperpigmentation; Inhibitory Concentration 50; Lignans; Melanins; Melanoma, Experimental; Molecular Structure; Monophenol Monooxygenase; Pigmentation; Saururaceae

Arbutin has been used as a whitening agent in cosmetic products. Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of the tyrosinase enzyme could be used for cosmetic skin whitening. A recent study has reported that arbutin decreases melanin biosynthesis through the inhibition of tyrosinase activity. However, this inhibitory mechanism of arbutin was not sufficiently demonstrated in skin tissue models. We found that arbutin both inhibits melanin production in B16 cells induced with alpha-MSH and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of alpha-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues. These results suggest that arbutin may be a useful agent for skin whitening.

Topics: Agaricales; alpha-MSH; Animals; Arbutin; Cell Line, Tumor; Cell Survival; Cosmetics; Dermatologic Agents; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Guinea Pigs; Humans; Hyperpigmentation; Melanins; Melanoma, Experimental; Middle Aged; Monophenol Monooxygenase; Organ Culture Techniques; Skin; Skin Pigmentation

Epidermal melanocytes synthesize melanin pigments and transfer them to keratinocytes, which is responsible for skin pigmentation. However, abnormal accumulation of melanin pigments causes hyperpigmentation disorders, which are substantially improved with treatment of tyrosinase inhibitor. In our ongoing study, Torilis japonica DC. (Umbelliferae) was found to inhibit melanin production. A goal of this study is to elucidate the hypopigmenting principle of T. japonica. A sesquiterpene structure of torilin was isolated from the plant extracts via bioassay-guided phytochemical analysis. Torilin dose-dependently inhibited melanin production, with an IC(50) value of 25 microM, in alpha-melanocyte stimulating hormone (alpha-MSH)-activated B16 melanoma cells. Arbutin, a positive control of skin whitener, also inhibited alpha-MSH-induced melanin production with an IC(50) value of 170 microM. As to the mode of action, torilin downregulated alpha-MSH-induced protein levels of tyrosinase without directly inhibiting catalytic activity of the enzyme. Taken together, this study shows that torilin contributes to the hypopigmenting principle of T. japonica, and suggests its pharmacological potential in melanin-associated hyperpigmentation disorders.

Topics: alpha-MSH; Animals; Apiaceae; Arbutin; Dermatologic Agents; Dose-Response Relationship, Drug; Down-Regulation; Fruit; Hyperpigmentation; Inhibitory Concentration 50; Melanins; Melanoma, Experimental; Mice; Monophenol Monooxygenase; Phytotherapy; Plant Extracts; Sesquiterpenes, Guaiane; Skin; Skin Neoplasms; Skin Pigmentation

Disorders, such as age spots, melasma and hyperpigmentation at sites of actinic damage, emanate from the augmentation of an increased amount of epidermal melanin.. The ineptness of current therapies in treating these conditions, as well as high cytotoxicity, mutagenicity, poor skin penetration and low stability of skin-depigmenting formulations led us to investigate new compounds that meet the medical requirements for depigmentation agents. We have shown previously that the tyrosinase inhibitor deoxyArbutin (dA) is a more effective and less toxic skin lightener than hydroquinone (HQ).. The efficacy and reversibility of dA and its derivatives on inhibiting tyrosine hydroxylase and DOPAoxidase was assessed using standard assays.. dA and its second-generation derivatives inhibit tyrosine hydroxylase and DOPAoxidase activities of tyrosinase dose dependently thereby inhibiting melanin synthesis in intact melanocytes, when used at concentrations that retain 95% cell viability in culture. This depigmenting effect was completely reversible when the compounds were removed. Tyrosinase inhibition was also observed in vitro when tested using human and purified mushroom tyrosinase, establishing that they are direct enzyme inhibitors. Lineweaver-Burk reciprocal plot analysis using mushroom tyrosinase illustrated that dA and its derivatives are more robust competitive inhibitors than HQ, when tyrosine is used as substrate.. Thus, dA and its second-generation derivatives, which inhibit melanogenesis at safe concentrations by specifically acting on the tyrosinase enzyme at a post-translational level, are promising agents to ameliorate hyperpigmented lesions or lighten skin.

Topics: Arbutin; Dopamine Agents; Enzyme Inhibitors; Humans; Hyperpigmentation; Melanocytes; Monophenol Monooxygenase; Tyrosine 3-Monooxygenase

Modulation of melanogenesis in the melanocytes can be achieved using chemicals that share structural homologies with the substrate tyrosine and as thus competitively inhibit the catalytic function of tyrosinase. We have developed a new tyrosinase inhibitor, deoxyArbutin (dA), based on this premise. DeoxyArbutin demonstrates effective inhibition of mushroom tyrosinase in vitro with a Ki that is 10-fold lower that hydroquinone (HQ) and 350-fold lower than arbutin. In a hairless, pigmented guinea pig model, dA demonstrated rapid and sustained skin lightening that was completely reversible within 8 weeks after halt in topical application. In contrast, HQ induced a short but unsustained skin lightening effect whereas kojic acid and arbutin exhibit no skin lightening effect. Results from a panel of safety tests supported the overall establishment of dA as an actionable molecule. In a human clinical trial, topical treatment of dA for 12 weeks resulted in a significant or slight reduction in overall skin lightness and improvement of solar lentigines in a population of light skin or dark skin individuals, respectively. These data demonstrate that dA has potential tyrosinase inhibitory activity that can result in skin lightening and may be used to ameliorate hyperpigmentary lesions.

Topics: Agaricales; Animals; Arbutin; Cell Proliferation; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Enzyme Inhibitors; Escherichia coli; Guinea Pigs; Humans; Hydroquinones; Hyperpigmentation; Immunosuppressive Agents; Kinetics; Lentigo; Light; Lymph Nodes; Mice; Mice, Inbred CBA; Models, Chemical; Monophenol Monooxygenase; Skin; Skin Pigmentation; Time Factors