The Potential Depigmenting Activity of Retinaldehyde

Abstract

Background: Retinoids have been reported to exert depigmenting activity. Unlike most depigmenting agents that target tyrosinase, they are not phenolic agents and may act via different mechanisms. Objectives: We analysed the properties of retinaldehyde (RAL), a precursor of retinoic acid (RA), as a skin-lightening agent in various models. Methods: The viability and the depigmenting properties of RAL were assessed in murine melanocytes, in human reconstructed epidermis, and in mice and guinea pigs. The melanin content and cytotoxicity were assessed in melanocytes; in 3-dimensional models, the melanin concentration and the number of active melanocytes were determined. Results: RAL was taken up by melanocytes and mostly metabolised to retinol and retinyl esters, and to a lesser extent to RA. RAL decreased the melanin concentration of guinea pig ears and mouse tails by 54 and 74%, respectively, and decreased the number of active melanocytes by 42 and 77%, respectively. In reconstructed epidermis the melanin concentration was increased by 52%, whereas the number of active melanocytes decreased by 44%. Conclusion: RAL exerts a significant depigmenting activity with a mode of action that looks different from that of RA. Our data suggest a skin-lightening effect related to a melanolytic action (i.e. a decrease in melanin concentration, whatever the mechanism) rather than to melanocytotoxicity, besides other still unknown actions of RAL on melanocytes.

The Combination of a Retinoid, a Phenolic Agent and an Antioxidant Improves Tolerance while Retaining an Optimal Depigmenting Action in Reconstructed Epidermis

“…2a, b), whereas RAL was toxic to both cells at concentrations >1 µ M and with an IC 50 value of 2.5 µ M [22]. The IC 50 value for total melanin content was 7 and 20 µ M for PER and TG, respectively; when expressing the melanin/MTT formazan (the reduced form of MTT), corresponding to the melanin content per viable cell, the IC 50 value was 20 µ M for both PER and TG (fig.…”

Clinical and Instrumental Evaluation of the Efficacy of a New Depigmenting Agent Containing a Combination of a Retinoid, a Phenolic Agent and an Antioxidant for the Treatment of Solar Lentigines

“…Retinoids have been reported to exert depigmenting activity [11]. In particular RAL, a precursor of retinoic acid (RA), acts as a skin-lightening agent in various models [12] and has been reported to have both antioxidant and depigmenting properties [13]. …”

“…RAL, besides being a transient form to the biologically active forms of vitamin A, exerts a specific non-melanocytotoxic skin-lightening activity. The epidermal hyperplasia induced by RAL leads to the dispersion of melanin deposits in a higher volume of tissue, corresponding to a decreased tissue concentration [12]. …”

“…Another option is to convert tyrosinase to dopaquinone in the presence of hydrogen peroxide and a peroxidase, in the absence of tyrosinase. In these conditions a reducing agent can have a skin-lightening action [12]. It has been shown in vitro that δ-tocopherol, a lipophilic antioxidant of the stratum corneum, has a higher penetration profile and reducing power than the more common α-tocopherol [8].…”

“…It has been shown in vitro that δ-tocopherol, a lipophilic antioxidant of the stratum corneum, has a higher penetration profile and reducing power than the more common α-tocopherol [8]. In reconstructed epidermis, the presence of δ-tocopherol prevented the toxicity observed with RAL alone [12]. …”