Comparison of the antimelanogenic effects of p-coumaric acid and its methyl ester and their skin permeabilities

Background: p-Coumaric acid (PCA) inhibits human tyrosinase (TYR) activity and melanin synthesis in human epidermal melanocytes. Objective: The purpose of the current study was to examine the potential of PCA and its hydrophobic derivative, methyl p-coumarate (MPC), as hypopigmenting agents for topical use. Methods: PCA and MPC were comparatively tested against in vitro human TYR enzyme activity and cellular melanin synthesis in human epidermal melanocytes. Permeation studies were undertaken using an artificial lipophilic membrane and an excised porcine skin. In vivo hypopigmenting efficacy was assessed on the skin of melanin-possessing hairless mice exposed to UVB. Results: Although PCA was a stronger inhibitor than MPC against TYR activity in vitro, the former inhibited cellular melanin synthesis less effectively than the latter. A non-cell based permeability assay indicated that PCA was practically impermeable through the lipophilic barrier while MPC was highly permeable. In contrast, an ex vivo skin permeation study demonstrated that topically applied PCA in the form of a cream can diffuse into the aqueous medium underneath the skin. No MPC was released from a MPC cream but PCA was released instead as a bio-converted product. Topical application of PCA cream attenuated the UVB-induced erythema formation and pigmentation in mice models, more effectively compared with MPC cream. Conclusion: PCA may be useful as an active ingredient for topical applications for a hypopigmenting effect. MPC has potential as a hypopigmenting agent but requires rather invasive methods for its delivery to the target cells. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.