Salicyloyl‐phytosphingosine: a novel agent for the repair of photoaged skin

Abstract

In recent years the importance of sphingolipids (cerebrosides, sphingomyelin, ceramides, sphingosine-1-phospate, etc.) in skin biology is receiving an increasing interest. Not only are ceramides essential for the barrier function of the skin, especially through their phytosphingosine, sphingosine and 6-hydroxysphingosine derivatives, they are now also known to be cell-signalling mediators which can improve epidermal differentiation. However, their effects on dermal anti-ageing markers and reduction of wrinkles have not been established. In this study, we were interested in the effects of a sphingolipid derivative, salicyloyl-phytosphingosine (SP), because of the known independent beneficial effects of salicylic acid and phytosphingosine on skin. Both of these agents are known to reduce the activities of the activator protein-1 transcription factor, in a manner similar to that observed with retinoic acid (RA) treatment. Through this mechanism, RA was shown to reduce the levels of matrix metalloproteases (MMPs) and the increase levels of extracellular matrix proteins. Therefore, we examined the effects of SP on procollagen-I synthesis in fibroblasts in vitro, its effects in vivo on the expression of dermal markers such as fibrillin-1, procollagen-I and MMP-1 immunochemically in biopsies taken from a short-term occluded patch test protocol and, its effects on periorbital wrinkle reduction over 4 weeks using Fast Optical In Vivo Topometry of Human Skin. In vitro we observed a significant increase in the production of procollagen-I by adult human fibroblasts (two fold increase, P < 0.01) which encouraged us to test the effects of SP in vivo. Initially, test products (SP at 0.05% and 0.2%, all-trans RA (0.025%) and vehicle were applied under occlusion for 8 days prior to biopsy and histological assessment in photoaged volunteers (n = 5). Increased deposition of fibrillin-1 and procollagen-I, together with reductions in the levels of MMP-1, were observed for the SP treatments (P < 0.05). Similar effects were observed for RA, except for the increases in procollagen-I. With these beneficial effects on the basement membrane and papillary dermal markers, we evaluated the effects of SP in an oil-in-water (O/W) cream for its effects in reducing the appearance of periorbital wrinkles in a 4-week, half-face clinical study compared to placebo cream (moderately photoaged female subjects aged 41-69 years; n = 30). Clear reductions in wrinkle depth and Rz (skin smoothness) together with Ra (skin roughness) parameters were observed (P < 0.05), indicating an anti-wrinkle benefit. In conclusion, this series of studies demonstrated for the first time that a ceramide derivative, such as that SP, was a novel agent for the repair of photoaged skin and highlight its effects at the cellular, tissue and organ levels.

Effects of sphingoid bases on the sphingolipidome in early keratinocyte differentiation

“…Inhibition of lipid metabolism and transport leads to improper barrier function (9)(10)(11)(12). Sphingolipids were shown to improve barrier function, dermatitis, acne and photodamage (13)(14)(15)(16)(17).…”

Antifaltencremes

“…die Kollagenneosynthese stimulieren kann. So konnte eine In-vivo-Studie mit placebokontrolliertem Design durch die Anwendung einer 0,2%igen Salicyloyl-Phytosphingosin-Zubereitung einen signifikanten Anstieg von Fibrillin I, von Pro-Kollagen I und eine signifikante Abnahme der MMP-1-Aktivität histopathologisch belegen [9]. Eine weitere placebokontrollierte Studie konnte bereits nach 4 Tagen eine Abnahme des transepidermalen Wasserverlustes (TEWL) um 9,6 Einheiten aufzeigen.…”

“…Eine weitere placebokontrollierte Studie konnte bereits nach 4 Tagen eine Abnahme des transepidermalen Wasserverlustes (TEWL) um 9,6 Einheiten aufzeigen. Nach 4-wöchiger 2-mal täglicher periorbitaler Applikation von 0,2%igem Salicyloyl-Phytosphingosin wurden mithilfe der FOITS-Messtechnik eine signifikante Reduktion der Hautoberflächenrau-igkeit und der Faltentiefe am Auge nachgewiesen [9]. [11].…”

Topical ceramides neither enhance UVB‐induced apoptosis in normal human keratinocytes nor affect viability in UVB‐irradiated reconstructed human epidermis

“…In the stratum corneum (SC), at least 12 classes comprising approximately 350 different molecular species have been identified (1,2). They are composed of one of four sphingolipid bases: sphingosine, dihydrosphingosine, 6-hydroxysphingosine and phytosphingosine, which are attached either to saturated, unsaturated, a-hydroxylated or x-hydroxylated fatty acids of various chain length.…”