This study indicates that in an in vivo 12-day patch test an over-the-counter cosmetic product can induce changes in photoaged dermal extracellular matrix, which are indicative of repair.

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BackgroundVery few over-the-counter cosmetic ‘anti-ageing’ products have been subjected to a rigorous double-blind, vehicle-controlled trial of efficacy. Previously we have shown that application of a cosmetic ‘anti-ageing’ product to photoaged skin under occlusion for 12 days can stimulate the deposition of fibrillin-1. This observation infers potential to repair and perhaps clinically improve photoaged skin.ObjectiveWe examined another similar over-the-counter cosmetic ‘anti-ageing’ product using both the patch test assay and a 6-month double-blind, randomized controlled trial (RCT), with a further 6-month open phase to assess clinical efficacy in photoaged skin.MethodsFor the patch test, a commercially available test product and its vehicle were applied occluded for 12 days to photoaged forearm skin (n=10) prior to biopsy and immunohistochemical assessment of fibrillin-1; all-trans retinoic acid (RA) was used as a positive control. Sixty photoaged subjects were recruited to the RCT (test product, n = 30 vs. vehicle, n = 30; once daily for 6 months, face and hands) with clinical assessments performed at recruitment and following 1, 3 and 6 months of use. Twenty-eight volunteers had skin biopsies (dorsal wrist) at baseline and at 6 months treatment for immunohistochemical assessment of fibrillin-1 (test product, n=15; vehicle, n=13). All volunteers received the test product for a further 6 months. Final clinical assessments were performed at the end of this open period.ResultsIn the 12-day patch test assay, we observed significant immunohistological deposition of fibrillin-1 in skin treated with the test product and RA compared with the untreated baseline (P=0·005 and 0·015, respectively). In the clinical RCT, at 6 months, the test product produced statistically significant improvement in facial wrinkles as compared to baseline assessment (P = 0·013), whereas vehicle-treated skin was not significantly improved (P = 0·11). After 12 months, there was a significant benefit of the test product over that projected for the vehicle (70% vs. 33% of subjects improving; combined Wilcoxon rank tests, P=0·026). There was significant deposition of fibrillin-1 in skin treated for 6 months with the test product [(mean ± SE) vehicle 1·84 ± 0·23; test product 2·57 ± 0·19; ancovaP=0·019).ConclusionsIn a double-blind RCT, an over-the-counter cosmetic ‘anti-ageing’ product resulted in significant clinical improvement in facial wrinkles, which was associated with fibrillin-1 deposition in treated skin. This study demonstrates that a cosmetic product can produce significant improvement in the appearance of wrinkles and further supports the use of fibrillin-1 as a robust biomarker for the repair of photoaged dermis.

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.