Potassium 4-Methoxysalicylate (4MSK) Exerts a Skin Lightening Effect by Acting on Melanocytes and Keratinocytes

Background: Hyperpigmentation is a common acquired disorder that can be a cosmetic concern for many individuals. To reduce and prevent hyperpigmentation, numerous skin lightening agents have been developed. Potassium 4-methoxysalicylate (4MSK) is a skin lightening agent that was approved as an active skin lightening ingredient of quasi-drugs by the Ministry of Health, Labour and Welfare of Japan in 2003. For over 20 years, 4MSK has been widely used in quasi-drug and cosmetic products. However, the mechanism of action and efficacy of 4MSK on skin pigmentation and skin lightness have not been publicly reported.
Aims: This study aimed to assess the mechanism of action and the efficacy of 4MSK on facial pigmentation.
Methods: The mechanism of action of 4MSK on epidermal cells was investigated using human melanocytes, human keratinocytes, and human 3D epidermal equivalents. The efficacy of 4MSK on facial pigmentation was evaluated by a human clinical study, which is a double blind, split-face, placebo-controlled, paired-design study.
Results: 4MSK significantly suppressed melanin content in cultured human melanocytes and a 3D epidermal equivalent. It also promoted gene expression of differentiation markers of human keratinocytes. In the clinical study, a 4MSK formulation significantly increased skin lightness values in both pigmented and non-pigmented areas of cheek skin. In addition, it reduced the desquamation area ratio of the cheek.
Conclusions: 4MSK reduces skin pigmentation and contributes to brighter skin by acting on both melanocytes and keratinocytes.

MelanoDerm, MEL-300-A, EPI-100-NMM-113 skin lightening, skin brightening, pigmentation, potassium 4-methoxysalicylate, macroscopic lightening, melanin assay, NaOH melanin extraction, Fontana-Masson staining, filaggrin, loricrin, Hoechst 33342

potassium 4-methoxysalicylate