p44/42 MAPK signaling is a prime target activated by phenylethyl resorcinol in its anti-melanogenic action

Kang, Mingyeong; Park, See‐Hyoung; Park, Se Jin; Oh, Sae Woong; Yoo, Ju Ah; Kwon, Ki-Won; Kim, Jangsoon; Yu, Eunbi; Cho, Jae Youl; Lee, Jongsung

doi:10.1016/j.phymed.2019.152877

Cited by 16 publications

(9 citation statements)

References 28 publications

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“…However, the experiment was conducted under infinite dose conditions and does not simulate typical amounts of a topical formulation that consumers apply to skin . Recently, Kang and Park probed the mechanism of the anti‐melanogenic activity of PR via a series of in vitro assays including assessment of cell survival, melanin content, cellular tyrosinase activity, real‐time PCR analysis, luciferase‐reporter assay, Western blot analysis, and ELISA assay of cyclic AMP (cAMP), protein kinase A (PKA), cAMP response element binding (CREB) protein and mitogen‐activated protein kinases (MAPKs). These authors reported that PR can attenuate melanogenesis by activating p44/42 MAPK which is a kinase that regulates signalling pathways mediating melanogenesis in melanocytes.…”

Section: Introductionmentioning

confidence: 99%

Characterization and topical delivery of phenylethyl resorcinol

Zhang¹,

Sil

Kung³

et al. 2019

Intern J of Cosmetic Sci

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Objective Phenylethyl resorcinol (PR) has been used widely in the personal care industry as a novel skin lightening ingredient. Surprisingly, there is only limited information describing the physicochemical properties of this active. Therefore, the primary objective of this study was to perform a comprehensive characterization of PR. A secondary objective was to investigate the delivery of this molecule to mammalian skin. Methods Phenylethyl resorcinol was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and nuclear magnetic resonance (NMR). A new high‐performance liquid chromatographic (HPLC) method for analysis of PR was developed and validated. The log P (octanol water partition coefficient), value, solubility and short‐term stability of PR in a series of vehicles were also determined using HPLC. The evaporation of the selected vehicles was examined using dynamic vapour sorption (DVS). The permeation profiles of PR were investigated under finite dose conditions in porcine and human skin. Results The melting point of PR was determined to be 79.13 °C and the measured log P (octanol water partition coefficient) at 21 °C was 3.35 ± 0.03. The linearity of the HPLC analytical method was confirmed with an r2 value of 0.99. Accuracy of the method was evaluated by average recovery rates at three tested concentrations, and the values ranged from 99 to 106%. The limit of detection (LOD) and limit of quantification (LOQ) were 0.19 and 0.57 μg mL−1, respectively. The solubility of PR in PG, DMI, glycerol was within the range of 367 to 877 mg mL−1. The stability of PR in tested solvents was also confirmed by the 72 h stability studies. From the DVS studies, 70–125% of applied formulations were recovered at 24 h. The permeation through porcine skin at 24 h ranged from 4 to 13 μg cm−2, while the corresponding amounts of PR delivered through human skin were 2 to 10 μg cm−2. Conclusion The physicochemical properties of PR confirm it is suitable for dermal delivery. In this study, propylene glycol was the most promising vehicle for PR delivery to human skin. Future work will expand the range of vehicles studied and explore the percutaneous absorption from more complex formulations.

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Section: Introductionmentioning

confidence: 99%

Characterization and topical delivery of phenylethyl resorcinol

Zhang¹,

Sil

Kung³

et al. 2019

Intern J of Cosmetic Sci

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“…It induced protein level of microphthalmia-associated transcriptional factor (MITF) and down-regulated the expression of its downstream genes such as tyrosinase and tyrosinase-related protein (TRP-2). 13 Nano-microneedling is a relatively new treatment approach that has many advantages, such as convenience, time efficiency, and decreased pain on use. It allows the skin barrier function to recover faster and the transdermal drug delivery to be more efficient.…”

Section: Discussionmentioning

confidence: 99%

“…Kang et al indicated that the anti-melanogenic activity of PR was mediated by activation of p44/42 mitogen-activated protein kinases (MAPK). They found that PR increased phosphorylation of p44/42 MAPK, and its upstream molecules such as MEK1/2 and Src.It induced protein level of microphthalmia-associated transcriptional factor (MITF) and down-regulated the expression of its downstream genes such as tyrosinase and tyrosinase-related protein (TRP-2) 13.…”

mentioning

confidence: 99%

Clinical efficacy and safety of nano‐microneedle‐assisted phenylethyl resorcinol for the treatment of infraorbital dark circles

Chen

et al. 2020

J of Cosmetic Dermatology

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Infraorbital dark circles are defined as a symptom that presents darkness under infraorbital eyelids. Throughout cultures, social views are similar, in that infraorbital dark circles contribute to a tired, aging, and even sad looks. 1 It is reported that a woman in the United States spends an average of $15 000 on cosmeceuticals in her lifetime, of which under-eye concealers were the majority, 2 reflecting people's great concern about periocular problems. Possible etiologic factors of the dark circles include dermal melanin deposition, superficial location of vasculature, shadowing due to skin laxity, and so on. 3 This multifactorial etiology often requires a multimodal therapeutic approach, such as topical de-pigmenting agents, laser therapy, and surgical intervention. 4 Phenylethyl resorcinol (PR), also known as SymWhite ® 377, is a potent inhibitor of tyrosinase. It has been reported to be one of the strongest skin-lightening agents and 22-fold more effective than kojic acid. 5-7

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“…In mice and humans, both melanoma cells and melanocytes share similarities in melanin production [27,28]. Thus, we used four types of cell models for in vitro experiments, including two mouse-cell models [mouse melanoma cell line B16F10 and mouse melanocyte cell line (Melan-a)] and two human models [human melanoma cell line MNT1 and primary epidermal melanocytes (HEMs)].…”

Section: Cytotoxicity Of the Rbfpmentioning

confidence: 99%

Evaluation of a resorufin-based fluorescent probe for tyrosinase detection in skin pigmentation disorders

Zeng

Jiang

et al. 2021

Bio-des. Manuf.

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Purpose Skin pigmentation disorders, such as vitiligo and melasma, are difficult to diagnose in the early stages, but abnormal tyrosinase levels and tyrosinase activity are potential indicators. Some resorufin-based fluorescence probes (RBFPs) have been designed to detect tyrosinase in tumors, but they have not been used in skin pigmentation disorders. In this study, one of these RBFPs (synthesized by resorufin salt coupled with 3-(bromomethyl)phenol) was evaluated comprehensively. Methods The RBFP was tested in different kinds of mouse and human skin cells, as well as in in vivo models, including zebrafish, guinea pigs, and Sprague-Dawley rats. In addition, small interfering RNAs (siRNAs), kojic acid, and 1-phenyl-2-thiourea (PTU) were used to inhibit tyrosinase levels or tyrosinase activity. Results This probe successfully detected tyrosinase and emitted red fluorescence in melanoma cells and melanocytes. Fluorescence was also observable in zebrafish and on the skin of guinea pigs when using the RBFP. In mouse and human cells, the RBFP showed good selectivity to tyrosinase. Moreover, in the case of decreased tyrosinase levels or activity caused by siRNAs, kojic acid, or PTU, the probe was sensitive to these changes. Further, the RBFP showed no toxic effects at concentrations of < 20 μmol/L, both in vitro and in vivo. Conclusions Our findings indicate the value and limitations of the RBFP in tyrosinase detection, but suggest the need for further improvement of fluorescent probes in the diagnosis of skin pigmentation disorders.Jing Chen and Qinghai Zeng contributed equally to this work.

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p44/42 MAPK signaling is a prime target activated by phenylethyl resorcinol in its anti-melanogenic action

Cited by 16 publications

References 28 publications

Characterization and topical delivery of phenylethyl resorcinol

Characterization and topical delivery of phenylethyl resorcinol

Clinical efficacy and safety of nano‐microneedle‐assisted phenylethyl resorcinol for the treatment of infraorbital dark circles

Evaluation of a resorufin-based fluorescent probe for tyrosinase detection in skin pigmentation disorders

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