Hydroquinone-Induced Depigmentation

Jow, Tiffany; Hantash, Basil M.

doi:10.1097/01.der.0000438425.56740.8a

Cited by 40 publications

(11 citation statements)

References 17 publications

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“…Chemical peeling and laser treatment are frequently performed, but they have side effects, such as dermatitis and recurring pigmentation [16,17]. Hydroquinone is primarily used as a pharmacotherapeutic, but it can potentially cause skin irritation, allergies, mutations, and cancer [18]. In the cosmetics field, skin lightening functional cosmetics containing arbutin, niacinamide, and vitamin C derivatives dominate, but the satisfaction of consumers regarding their safety and skin lightening efficacy is low [19].…”

Section: Introductionmentioning

confidence: 99%

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

Boo

Jo²,

et al. 2020

Biomedicines

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A previous study identified certain low molecular anti-melanogenic peptides that share a common sequence with α-melanocyte stimulating hormone (MSH) and end with a glycinamide moiety. Glycinamide itself also showed anti-melanogenic activity in cell-based assays, but neither glycine nor acetyl glycinamide were active, which indicated a special structure and activity relationship. The aim of this study was to examine the skin depigmentation efficacy of glycinamide hydrochloride in human subjects. The primary skin irritation potential of glycinamide hydrochloride was evaluated by patch testing in 30 human subjects. The skin depigmentation efficacy of glycinamide hydrochloride was evaluated in a double-blinded clinical test in 21 human subjects. The test product and a control product were applied to designated sites on the right or left side of the face twice daily for eight weeks. Skin color parameters, i.e., the melanin index, the L* value (representing skin lightness), a* value (redness), and b* value (yellowness) were measured using instruments. The individual topology angle (ITAo, representing skin color) was calculated from L* and b values. The degree of skin pigmentation was visually assessed by two testers. The primary skin irritation test showed that a solution containing glycinamide hydrochloride up to 10% did not induce any adverse skin responses. In the efficacy test, the test product significantly reduced the melanin index, and increased L* value and ITAo after two weeks of application relative to the baseline value at the start of the test. It also significantly lowered the degree of pigmentation after 6 weeks of application, relative to the baseline value. Differences in the melanin index, L* value, ITAo and the degree of pigmentation between the test and control groups became statistically significant after six weeks or eight weeks of application. No signs of skin irritation were observed during the efficacy test. The present study suggests that glycinamide hydrochloride has great potential to be used in the control of skin hyperpigmentation.

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Section: Introductionmentioning

confidence: 99%

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

Boo

Jo²,

et al. 2020

Biomedicines

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“…Consequently, certain antidiabetic drugs such as voglibose [ 20 ] and acarbose [ 21 ], which are known to inhibit α-glucosidase activity, also suppress melanogenesis. The use of commercial depigmenting agents, hydroquinone (HQ), kojic acid (KA) and arbutin, has been limited since they inhibit tyrosinase in a manner that cannot be fully reversed [ 22 ] and cause deleterious effects such as erythema, contact dermatitis, genotoxicity, and carcinogenicity [ 23 , 24 ]. As the process of melanogenesis involves a multi-step pathway, compounds which can target different steps in this pathway provide an attractive target for melanogenesis inhibition.…”

Section: Introductionmentioning

confidence: 99%

CMT-308, a Nonantimicrobial Chemically-Modified Tetracycline, Exhibits Anti-Melanogenic Activity by Suppression of Melanosome Export

Goenka

Simon

2020

Biomedicines

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CMT-308 is a nonantimicrobial chemically-modified tetracycline (CMT), which we have previously shown exhibits antifungal activity and pleiotropic anti-inflammatory activities, including inhibition of the enzymatic activity of matrix metalloproteinases (MMPs). Based on its chemical structure, we hypothesized that CMT-308 could inhibit melanogenesis and might be a candidate for the treatment of skin hyperpigmentation disorders which occur due to unregulated melanin biosynthesis and/or transport. CMT-308 was first studied for any effects on activity of the enzyme tyrosinase in vitro using a purified preparation of mushroom tyrosinase; the mode of inhibition of the soluble fungal enzyme was evaluated by Lineweaver-Burk and Dixon plots as well as by non-linear least squares fitting. Next, the effects of CMT-308 were tested in mammalian cell cultures using B16F10 mouse melanoma cells and further validated in darkly-pigmented human melanocytes (HEMn-DP). Our results showed that micromolar concentrations of CMT-308 inhibited mushroom tyrosinase enzyme activity, using the first two substrates in the melanogenesis pathway (l-tyrosine and l-3,4-dihydroxyphenylalanine (l-DOPA)); CMT-308 inhibited mushroom tyrosinase primarily via a mixed mode of inhibition, with the major contribution from a competitive mode. In B16F10 cell cultures, CMT-308 (10 µM) significantly diminished total melanin levels with a selective reduction of extracellular melanin levels, under both basal and hormone-stimulated conditions without any cytotoxicity over a duration of 72 h. Studies of potential mechanisms of inhibition of melanogenesis in B16F10 cells showed that, in mammalian cells, CMT-308 did not inhibit intracellular tyrosinase activity or the activity of α-glucosidase, an enzyme that regulates maturation of tyrosinase. However, CMT-308 suppressed MITF protein expression in B16F10 cells and showed copper chelating activity and antioxidant activity in a cell-free system. The significantly lower extracellular melanin levels obtained at 10 µM indicate that CMT-308’s anti-melanogenic action may be attributed to a selective inhibition of melanosome export with the perinuclear aggregation of melanosomes, rather than a direct effect on the tyrosinase-catalyzed steps in melanin biosynthesis. These results were validated in HEMn-DP cells where CMT-308 suppressed dendricity in a fully reversible manner without affecting intracellular melanin synthesis. Furthermore, the capacity of CMT-308 to inhibit melanosome export was retained in cocultures of HEMn-DP and HaCaT. In summary, our results offer promise for therapeutic strategies to combat the effects of hyperpigmentation by use of CMT-308 at low micromolar concentrations.

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“…Various approaches are available for the treatment of hyperpigmentation, such as chemical peeling, laser surgery, pharmacotherapy, and cosmetic camouflage [29][30][31], but these remain unsatisfactory. Hydroquinone is a commonly used treatment for skin pigmentation disorders that can be administered alone or in combination with other drugs, but it is associated with side effects such as irritation, allergy, and cancer [32]. Although various inhibitors of melanin synthesis are used in the cosmetic industry to control skin pigmentation, consumer satisfaction is low, and more effective skin lightening treatments are in high demand [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Screening of an Epigenetic Drug Library Identifies 4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-Phenyl-Benzeneacetamide that Reduces Melanin Synthesis by Inhibiting Tyrosinase Activity Independently of Epigenetic Mechanisms

Song

Hwang

et al. 2020

IJMS

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The aim of this study was to identify novel antimelanogenic drugs from an epigenetic screening library containing various modulators targeting DNA methyltransferases, histone deacetylases, and other related enzymes/proteins. Of 141 drugs tested, K8 (4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-phenyl-benzeneacetamide; HPOB) was found to effectively inhibit the α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis in B16-F10 murine melanoma cells without accompanying cytotoxicity. Additional experiments showed that K8 did not significantly reduce the mRNA and protein level of tyrosinase (TYR) or microphthalmia-associated transcription factor (MITF) in cells, but it potently inhibited the catalytic activity TYR in vitro (IC50, 1.1–1.5 µM) as compared to β-arbutin (IC50, 500–700 µM) or kojic acid (IC50, 63 µM). K8 showed copper chelating activity similar to kojic acid. Therefore, these data suggest that K8 inhibits cellular melanin synthesis not by downregulation of TYR protein expression through an epigenetic mechanism, but by direct inhibition of TYR catalytic activity through copper chelation. Metal chelating activity of K8 is not surprising because it is known to inhibit histone deacetylase (HDAC) 6 through zinc chelation. This study identified K8 as a potent inhibitor of cellular melanin synthesis, which may be useful for the treatment of hyperpigmentation disorders

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Hydroquinone-Induced Depigmentation

Cited by 40 publications

References 17 publications

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

CMT-308, a Nonantimicrobial Chemically-Modified Tetracycline, Exhibits Anti-Melanogenic Activity by Suppression of Melanosome Export

Screening of an Epigenetic Drug Library Identifies 4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-Phenyl-Benzeneacetamide that Reduces Melanin Synthesis by Inhibiting Tyrosinase Activity Independently of Epigenetic Mechanisms

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