Modulation of skin pigmentation by the tetrapeptide PKEK: in vitro and in vivo evidence for skin whitening effects

• Published in: Experimental dermatology Vol. 21; no. 2; pp. 140 - 146
• Main Authors: Marini, Alessandra, Farwick, Mike, Grether-Beck, Susanne, Brenden, Heidi, Felsner, Ingo, Jaenicke, Thomas, Weber, Monika, Schild, Jennifer, Maczkiewitz, Ursula, Köhler, Tim, Bonfigli, Adriana, Pagani, Valerie, Krutmann, Jean
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012; Blackwell
• Subjects: Adult; age spot; Aged; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - pharmacology; Ascorbic Acid - therapeutic use; Asian Continental Ancestry Group; Biological and medical sciences; Cells, Cultured; Colorimetry; Dermatology; Double-Blind Method; European Continental Ancestry Group; Female; Gene Expression - drug effects; Gene Expression - radiation effects; Humans; hyperpigmentation; Interleukin-1beta - genetics; Interleukin-6 - genetics; Interleukin-8 - genetics; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - radiation effects; Male; Medical sciences; Middle Aged; Monophenol Monooxygenase - genetics; Oligopeptides - pharmacology; Oligopeptides - therapeutic use; Pigmentary diseases of the skin; PKEK; Pro-Opiomelanocortin - metabolism; Skin - anatomy & histology; Skin - drug effects; Skin - metabolism; Skin - radiation effects; Skin Aging - drug effects; Skin Pigmentation - drug effects; Skin Pigmentation - radiation effects; skin whitener; tetrapeptide; Treatment Outcome; Tumor Necrosis Factor-alpha - genetics; Ultraviolet Rays; Skin disease; Pigmentation disorder; PKEK; Dermatology; age spot; In vitro; skin whitener; In vivo; hyperpigmentation; Hypermelanosis; Skin; Age; tetrapeptide
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.1600-0625.2011.01415.x

:  Uneven skin pigmentation is a significant cosmetic concern, and the identification of topically applicable molecules to address this issue is of general interest. We report that the tetrapeptide PKEK (Pro‐Lys‐Glu‐Lys) can exert skin whitening effects based on one in vitro and four double‐blinded vehicle‐controlled in vivo studies. (i) Treatment of human keratinocytes with PKEK significantly reduced UVB‐stimulated mRNA expression of interleukin (IL)‐6, IL‐8 and TNF‐α and, most importantly, proopiomelanocorticotropin (POMC), i.e. a gene encoding the pigmentation‐inducing soluble mediator α‐ (α‐MSH). (ii) PKEK treatment significantly inhibited UVB‐induced upregulation of genes encoding for IL‐1α, IL‐6, IL‐8, TNF‐α as well as POMC and tyrosinase in 10 healthy volunteers pretreated with PKEK for 4 weeks once daily. (iii) In a study enrolling 39 Caucasian women, facial pigment spots significantly faded after 6 weeks when PKEK was combined with the skin whitener sodium ascorbyl phosphate (SAP), whereas PKEK or SAP alone led to less pronounced fading of the pigment spots. (iv) Addition of PKEK enhanced the skin whitening potency of a SAP‐containing preparation if applied for 8 weeks to the back of hands of 19 Caucasians. (v) 27 Japanese women were treated on their faces twice daily with an SAP only or a PKEK+SAP‐containing formulation for 8 weeks. Application of PKEK+SAP significantly reduced skin pigmentation by 26% and by 18% according to SCINEXA score. We demonstrate that PKEK has the capacity to reduce UVB‐induced skin pigmentation and may be suited to serve as a skin tone–modulating agent in cosmetic products.