ABSTRACT
Skin is the essential barrier of the human body which performs multiple functions. Endogenous factors, in concert with external assaults, continuously affect skin integrity, leading to distinct structural changes that influence not only the skin appearance but also its various physiological functions. Alterations of the barrier functions lead to an increased risk of developing disease and side reactions, thus the importance of maintaining the integrity of the epidermal barrier and slowing down the skin aging process is evident. Salvia haenkei (SH) has been recently identified as a potential anti-senescence agent; its extract is able to decrease the level of senescent cells by affecting the IL1α release and reducing reactive oxygen species (ROS) generation. In this study, SH extract was tested on human keratinocyte cell line (HaCaT) exposed to stress factors related to premature aging of cells such as free radicals and ultraviolet B radiation. We confirmed that SH acts as scavenger of ROS and found its ability to restore the skin barrier integrity by reinforcing the cytoskeleton structure, sealing the tight junctions and increasing the migration rate of cells. Given these results, this work becomes relevant, identifying Salvia haenkei as a compound useful for anti-aging skin treatment in clinical performance.
Subject(s)
Keratinocytes/drug effects , Plant Extracts/pharmacology , Skin Aging/drug effects , Skin/drug effects , Cell Line , Cell Survival/drug effects , Cellular Senescence/drug effects , Humans , SalviaABSTRACT
Cellular senescence is a stable cell cycle arrest that is the causative process of aging. The PI3K/AKT/mTOR pathway is implicated in the control of cellular senescence and inhibitors of this pathway have been successfully used for life span prolongation experiments in mammals. PTEN is the major regulator of the PI3K/AKT/mTOR pathway and loss of PTEN promotes a senescence response termed PICS. Here we report a novel-screening assay, for the identification of compounds that block different types of senescence response. By testing a library of more than 3000 natural and chemical compounds in PTEN deficient cells we have found that an extract from Salvia haenkei (SH), a native plant of Bolivia is a potent inhibitor of PICS. SH also decreases replicative and UV-mediated senescence in human primary fibroblasts and in a model of in vitro reconstructed human epidermis. Mechanistically, SH treatment affects senescence driven by UV by interfering with IL1-α signalling. Pre-clinical and clinical testing of this extract by performing toxicity and irritability evaluation in vitro also demonstrate the safety of SH extract for clinical use as anti-aging skin treatment.