Different effects of five depigmentary compounds, rhododendrol, raspberry ketone, monobenzone, rucinol and <scp>AP</scp>736 on melanogenesis and viability of human epidermal melanocytes

Bae

et al. 2020

IJMS

Self Cite

Sugars are ubiquitous in organisms and well-known cosmetic ingredients for moisturizing skin with minimal side-effects. Glucose, a simple sugar used as an energy source by living cells, is often used in skin care products. Several reports have demonstrated that sugar and sugar-related compounds have anti-melanogenic effects on melanocytes. However, the underlying molecular mechanism by which glucose inhibits melanin synthesis is unknown, even though glucose is used as a whitening as well as moisturizing ingredient in cosmetics. Herein, we found that glucose significantly reduced the melanin content of α-melanocyte-stimulating hormone (MSH)-stimulated B16 cells and darkly pigmented normal human melanocytes with no signs of cytotoxicity. Furthermore, topical treatment of glucose clearly demonstrated its whitening efficacy through photography, Fontana-Masson (F&M) staining, and multi-photon microscopy in a pigmented 3D human skin model, MelanoDerm. However, glucose did not alter the gene expression or protein levels of major melanogenic proteins in melanocytes. While glucose potently decreased intracellular tyrosinase activity in melanocytes, it did not reduce mushroom tyrosinase activity in a cell-free experimental system. However, glucose was metabolized into lactic acid, which can powerfully suppress tyrosinase activity. Thus, we concluded that glucose indirectly inhibits tyrosinase activity through conversion into lactic acid, explaining its anti-melanogenic effects in melanocytes.

Section: Introductionmentioning

confidence: 99%

Glucose Exerts an Anti-Melanogenic Effect by Indirect Inactivation of Tyrosinase in Melanocytes and a Human Skin Equivalent

Bae

et al. 2020

IJMS

Self Cite

“…Moreover, LCA was shown not to be a substrate of tyrosinase, a critical issue for the toxicity of depigmenting agents in vivo as fully appreciated further to the case of rhododendrol, a phenolic depigmenting agent whose oxidation products generated by the action of tyrosinase proved to be toxic and able to induce leukoderma [31,32,33,34,35]. The nature of tyrosinase inhibition was explored using Lineweaver–Burk plots suggesting a mixed type mechanism.…”

Section: Introductionmentioning

confidence: 99%

Conjugation with Dihydrolipoic Acid Imparts Caffeic Acid Ester Potent Inhibitory Effect on Dopa Oxidase Activity of Human Tyrosinase

Micillo

Sirés-Campos

García‐Borrón

et al. 2018

IJMS

Caffeic acid derivatives represent promising lead compounds in the search for tyrosinase inhibitors to be used in the treatment of skin local hyperpigmentation associated to an overproduction or accumulation of melanin. We recently reported the marked inhibitory activity of a conjugate of caffeic acid with dihydrolipoic acid, 2-S-lipoylcaffeic acid (LCA), on the tyrosine hydroxylase (TH) and dopa oxidase (DO) activities of mushroom tyrosinase. In the present study, we evaluated a more lipophilic derivative, 2-S-lipoyl caffeic acid methyl ester (LCAME), as an inhibitor of tyrosinase from human melanoma cells. Preliminary analysis of the effects of LCAME on mushroom tyrosinase indicated more potent inhibitory effects on either enzyme activities (IC50 = 0.05 ± 0.01 μM for DO and 0.83 ± 0.09 μM for TH) compared with LCA and the reference compound kojic acid. The inhibition of DO of human tyrosinase was effective (Ki = 34.7 ± 1.1 μM) as well, while the action on TH was weaker. Lineweaver–Burk analyses indicated a competitive inhibitor mechanism. LCAME was not substrate of tyrosinase and proved nontoxic at concentrations up to 50 μM. No alteration of basal tyrosinase expression was observed after 24 h treatment of human melanoma cells with the inhibitor, but preliminary evidence suggested LCAME might impair the induction of tyrosinase expression in cells stimulated with α-melanocyte-stimulating hormone. All these data point to this compound as a valuable candidate for further trials toward its use as a skin depigmenting agent. They also highlight the differential effects of tyrosinase inhibitors on the human and mushroom enzymes.

“…Hyperpigmentation, which is induced by melanin overexpression, causes pigmentary disorders such as freckles, melasma and age spots . To address these issues, researchers have developed antimelanogenic agents such as kojic acid, arbutin and hydroquinone; however, numerous antimelanogenic agents have been shown to exert slight whitening effects or more severe adverse effects . Antimelanogenic agents usually target expression or activation of tyrosinase, the rate‐limiting enzyme in melanogenesis.…”

mentioning

confidence: 99%

“…4 To address these issues, researchers have developed antimelanogenic agents such as kojic acid, arbutin and hydroquinone; however, numerous antimelanogenic agents have been shown to exert slight whitening effects or more severe adverse effects. 5 Antimelanogenic agents usually target expression or activation of tyrosinase, the rate-limiting enzyme in melanogenesis. Although tyrosinase is the key regulatory enzyme in melanogenesis, tyrosinase-related protein (TYRP)-1 and TYRP-2, and premelanosome protein (PMEL) (also known as gp100) carry out important roles in regulating melanogenesis.…”

mentioning

confidence: 99%

Protopanaxatriol inhibits melanin synthesis through inactivation of the pCREB-MITF-tyrosinase signalling pathway in melanocytes

2018

Ginsenosides are major active components of ginseng, and have diverse pharmacological properties in traditional medicine. Recent reports have shown that ginsenosides modify skin physiology and mitigate skin disorders such as photoageing and hyperpigmentation. We evaluated the antimelanogenic efficacy of protopanaxatriol, a major category of ginsenosides, as a depigmenting agent. Protopanaxatriol significantly reduced intracellular and extracellular melanin content in a concentration-dependent manner in B16 melanoma cells treated with α-melanocyte-stimulating hormone. In normal human epidermal melanocytes, protopanaxatriol clearly decreased melanin synthesis and dendrite elongation. In addition, protopanaxatriol dramatically suppressed the expression of genes encoding the melanogenic proteins tyrosinase, tyrosinase-related protein-1 and -2, and microphthalmia-associated transcription factor through dephosphorylation of cAMP response element-binding protein. These results suggest that protopanaxatriol could be an effective candidate anti-melanogenic agent.