Background: Retinol (RE) is deeply involved in skin processes, therefore it is widely formulated in cosmetics, primarily as an anti-aging ingredient. Despite its efficacy, the safety profile of RE is controversial. Objectives: Pretinol (PRE) complex was formulated with two RE precursors, β -Carotene and Niacinamide, in order to deliver retinol-like skin benefits with healthier characteristics, as suming that skin enzymes will enable safe RE supply on spot. Methods: The expres sion levels of hyaluronic acid, Tumor Necrosis Factor alpha (TNF α ) and In terleukin 1 alpha (IL-1 α ), were measured using various skin models before and after exposure to PRE and RE. Full genome microarray was performed and the affected genes and pathways were analyzed. Results: Following fibroblasts exposure to PRE, the natural synthesis of hyaluronic acid is significantly elevated . Skin safety, demonstrated via cytokines expression on ex-vivo skin, results with TNF α and IL-1 α elevation by RE application. In contrary PRE significantly reduces TNF α while IL-1 α is not affected. These results establish skin safety advantage of PRE vs RE. Microarray results examined on skin equivalents reveal the involvement of PRE in inflammatory attenuation. Conclusions: Formulat ing RE precursors as a safe source for RE is partially supported. PRE presents a skin benefit in parallel to RE, while PRE characteristics are suggested to be safer to skin.
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