Anti-Glycation and Anti-Aging Properties of Resveratrol Derivatives in the in-vitro 3D Models of Human Skin.

Purpose: Human skin undergoes modifications affecting its structural properties and barrier functions involved in protection against age-related damage. Glycation is a non-enzymatic reaction between macromolecules and sugars causing alterations to the elastic fibers and premature aging of the skin. Glycation can be prevented by a range of bioactive molecules; however, at present only a few of them are validated for inclusion in cosmetic products. There is also a demand for reproducible in-vitro assays demonstrating the anti-aging effect of compounds on the skin. This study aimed to define the potential targets for screening and validation of anti-glycation activity of novel cosmetic candidates from natural products and to provide a plausible mechanism for their anti-aging potential based on 3D skin models. Methods: Dermal fibroblasts and 3D skin models were treated with glycation agent and topical applications of Resveratrol derivatives. The samples were analyzed for advanced glycation end products (AGEs) alongside an organization of elastic fibers and expression of proliferative, senescence, and oxidative stress markers by autofluorescence, immunocytochemistry and quantitative assays. Results: Accumulation of AGEs in the 3D skin model is associated with reduced stratification of the epidermis and re-organization of the collagen in the upper, cell-dense layer of the dermis. Treatment of dermal fibroblasts with Resveratrol, OxyResveratrol, Piceatannol, and Triacetyl Resveratrol ameliorates the effects of glycation consistent with cellular aging. Subsequent topical application of the compounds in skin models results in a reduction in glycation-induced AGEs, an increase in collagen expression and a stratification of the epidermis. Conclusion: Glycation could result in age-related alterations in the structural and cellular organizations of the superficial layers of the skin, which can be restored by Resveratrol derivatives, pointing to their promising capacities as bioactive ingredients in cosmetic products. Insight into the potential parameters affected by skin glycation could also serve as a reference for screening the bioactive molecules for cosmetic purposes.