A novel anti-melanogenic agent, KDZ-001, inhibits tyrosinase enzymatic activity

Hwang, Kyu-Seok; Yang, Jung Yoon; Lee, Joo Yun; Lee, Yu-Ri; Kim, Seong Soon; Kim, Geum Ran; Chae, Jin Sil; Ahn, Jin Hee; Shin, Dae-Seop; Choi, Tae–Young; Bae, Myung Ae

doi:10.1016/j.jdermsci.2017.11.004

Cited by 25 publications

(13 citation statements)

References 31 publications

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“…Melanin synthesis is a series of oxidative reactions, and multiple enzymes are involved in these processes such as tyrosinase and TRP-1 and TRP-2. Tyrosinase, a copper-containing metalloenzyme, acts as the rate-limiting enzyme in the melanogenic pathway and plays a crucial role in initiating melanin synthesis [ 23 , 24 ]. Tyrosine is oxidized by tyrosinase to l -DOPA and DOPAquinone.…”

Section: Discussionmentioning

confidence: 99%

Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction in B16F10 Cells

You

Liu

et al. 2018

IJMS

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Melanin is synthesized through a series of interactions catalyzed by melanogenic enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2; TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in catalysing the initial and limiting steps of melanogenesis. The melanin that results from melanogenesis has the protective effect of absorbing ultraviolet radiation. However, overproduction of melanin, in addition to altering the appearance of skin, may lead to skin disorders such as melasma, solar lentigo, and postinflammatory hyperpigmentation. Previous studies have revealed that sesamol is a strong antioxidant and a free radical scavenger. In this study, we investigated the effects of sesamol on the regulation of melanogenesis and related mechanisms in B16F10 cells. The results indicated that sesamol inhibited tyrosinase activity and melanogenesis induced by α-melanocyte-stimulating hormone (α-MSH) in B16F10 melanoma cells. Sesamol decreased the protein level of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, and TRP-1 by downregulating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathways that had been activated by α-MSH. Sesamol increased glycogen synthase kinase 3 beta (GSK3β), protein kinase B (AKT), and extracellular signal-related kinase (ERK) phosphorylation, thus inhibiting the transcription of MITF. Sesamol also inhibited melanin synthesis and tyrosinase expression by modulating ERK, phosphoinositide 3-kinase (PI3K)/AKT, p38, and c-Jun amino-terminal kinase (JNK) signalling pathways. These results indicate that sesamol acted as a potent depigmenting agent.

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Section: Discussionmentioning

confidence: 99%

Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction in B16F10 Cells

You

Liu

et al. 2018

IJMS

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“…Melanogenesis is a process involving the catalysis of tyrosine by tyrosinase, tyrosinase-related protein 1 (TRP1), tyrosinase-related protein 2 (TRP2)/dopachrome tautomerase (DCT), and microphthalmia-associated transcription factor (MITF) [10,11]. In melanogenesis, MITF is a major transcription factor that regulates melanogenic genes encoding tyrosinase and TRP2/DCT [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…Tyrosinase catalyzes dopachrome to 5,6-dihydroxyindole (DHI). Eumelanin is produced from a series of reactions between DHI and dihydroxyindole-2-carboxlic acid (DHICA) [10,11,21,22], while pheomelanin is produced by the condensation of dopaquinone with cysteine or glutathione into cysteinyl dopa or glutathionyl dopa [23,24]. In the process of melanogenesis, the rate-limiting enzyme, tyrosinase, is the key enzyme that initiates the process and catalyzes two subsequent reactions.…”

Section: Introductionmentioning

confidence: 99%

“…Till date, various inhibitors of melanogenesis-related enzymes have been identified for whitening effects and the control of skin pigmentation in the medicine and cosmetic industry [10,25,26]. Unfortunately, these inhibitors have undesirable side effects, owing to which the demand for alternative anti-melanogenic compounds has been increasing.…”

Section: Introductionmentioning

confidence: 99%

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Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents

Lee

Min

et al. 2020

IJMS

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Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase, which is the key enzyme in melanogenesis, identified using docking-based high throughput virtual screening of an in-house natural compound library followed by mushroom tyrosinase inhibition assay. Of the three compounds, gallacetophenone showed high anti-melanogenic effect in both human epidermal melanocytes and a 3D human skin model, MelanoDerm. The inhibitory effect of gallacetophenone on tyrosinase was elucidated by computational molecular modeling at the atomic level. Binding of gallacetophenone to the active site of tyrosinase was found to be stabilized by hydrophobic interactions with His367, Ile368, and Val377; hydrogen bonding with Ser380 and a water molecule bridging the copper ions. Thus, our results strongly suggested gallacetophenone as an anti-melanogenic ingredient that inhibits tyrosinase.

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“…Retinoic acid may cause developmental toxicity. Researchers have sought to identify safe skin whitening agents for the inhibition of hyperpigmentation in the skin [11,12]. Natural products or agents with antioxidant and tyrosinase-inhibiting activities are safer candidates for preventing hyperpigmentation [13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

Sesamol Inhibited Ultraviolet Radiation-Induced Hyperpigmentation and Damage in C57BL/6 Mouse Skin

You

Liu

et al. 2019

Antioxidants

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Melanin is synthesized through a series of oxidative reactions initiated with tyrosine and catalyzed by melanogenesis-related proteins such as tyrosinase, tyrosinase-related protein-1 (TRP-1), dopachrome tautomerase (TRP-2), and microphthalmia-associated transcription factor (MITF). Our previous study demonstrated that sesamol inhibited melanin synthesis through the inhibition of the melanocortin 1 receptor (MC1R)/MITF/tyrosinase pathway in B16F10 cells. In this study, sesamol was applied to C57BL/6 mouse skin to understand its activity with respect to skin pigmentation. The results indicated that ultraviolet (UV) B-induced hyperpigmentation in the C57BL/6 mouse skin was significantly reduced by topical application of sesamol for 4 weeks. Sesamol reduced the melanin index and melanin content of the skin. In addition, sesamol elevated the brightness (L* value) of the skin. Sesamol also reduced UVB-induced hyperplasia of epidermis and collagen degradation in dermis. In immunohistochemical staining, topical application of sesamol reduced UVB-induced tyrosinase, TRP-1, TRP-2, and MITF expression in the epidermis of the skin. These results demonstrated that sesamol is a potent depigmenting agent in the animal model.

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A novel anti-melanogenic agent, KDZ-001, inhibits tyrosinase enzymatic activity

Abstract: KDZ-001 inhibits melanin synthesis and has a potential for use in skin-whitening cosmetics.

Cited by 25 publications

References 31 publications

Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction in B16F10 Cells

Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction in B16F10 Cells

Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents

Sesamol Inhibited Ultraviolet Radiation-Induced Hyperpigmentation and Damage in C57BL/6 Mouse Skin

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