The skin, as the body’s outermost layer, constantly faces environmental stressors that accelerate the aging process. Factors such as ultraviolet radiation (UVR) and pollution, including Benzo[a]pyrene (BAP), induce oxidative damage, impair skin homeostasis, and lead to the accumulation of damaged proteins, ultimately contributing to premature skin aging and cellular senescence. Counteracting these effects by stimulating endogenous protective mechanisms is a crucial area of research in skincare. In this context, plant-derived extracts rich in bioactive compounds have garnered significant attention. Rose extracts, known to contain phenolic compounds with antioxidant properties, were considered as a potential solution to mitigate these age-related skin changes by modulating skin longevity pathways such as the AMP-activated protein kinase (AMPK), antioxidant defense, and autophagy. The study aimed to explore these potential benefits of a specific Rosa hybrid extract on human keratinocytes subjected to environmental stress.
Methods:
The researchers utilized a supercritical CO2 extraction method to obtain the active compounds from Rosa hybrid flowers. Primary human keratinocytes were then treated with various concentrations of this rose extract. To mimic environmental stress, the cells were exposed to Benzo[a]pyrene (BAP) followed by UV-A irradiation. The study assessed the impact of the rose extract on antioxidant defense (NRF2 levels), autophagy (LAMP2A levels, carbonylation levels), cellular senescence (P16INK4A), and cell proliferation (KI67) using in situ visualization and quantification. The involvement of the AMPK pathway was investigated by evaluating its phosphorylation state (P-AMPK/AMPK ratio, P-ACC levels) via Western blot and by using Compound C, a specific AMPK inhibitor, and AICAR, an AMPK activator.
Key Findings:
•The rose extract significantly increased the levels of NRF2 (a master regulator of antioxidant response) and LAMP2A (involved in chaperone-mediated autophagy) in human keratinocytes under basal conditions, suggesting enhanced antioxidant defense and detoxification mechanisms.
•Pre-treatment with the rose extract effectively mitigated the stress-induced increase in protein carbonylation levels (a marker of oxidative damage) and the number of P16INK4A-positive cells (a marker of cellular senescence) in keratinocytes exposed to BAP and UV-A.
•The rose extract also preserved the levels of KI67, a marker of cell proliferation, counteracting the cell growth arrest induced by stress.
•The beneficial effects of the rose extract in reducing carbonylation and cellular senescence were reversed by Compound C, a specific inhibitor of AMPK, indicating that these effects are mediated through the AMPK pathway.
•The rose extract activated the AMPK pathway, as evidenced by a significant increase in the phosphorylation of AMPK and its downstream target ACC in stressed keratinocytes.
•Chromatographic analysis of the rose extract identified a range of volatile and non-volatile compounds, including tannins, flavonoids, organic acids, monoterpenes, sesquiterpenes, and fatty acid derivatives.
This study provides novel insights into the protective mechanisms of a Rosa hybrid extract on skin cells subjected to environmental stress. The research demonstrates for the first time that this specific rose extract activates the AMPK pathway in human keratinocytes. This activation is crucial for mediating the extract’s antioxidant, anti-senescent, and pro-autophagic effects, ultimately protecting skin cells from oxidative damage, cellular senescence, and loss of proliferation induced by pollution and UV-A irradiation. Notably, the findings highlight a novel link between AMPK activation and the preservation of protein integrity by reducing oxidative protein modifications like carbonylation. These results underscore the significant potential of this Rosa hybrid extract as an active ingredient in cosmetic formulations aimed at mitigating age-related skin changes by targeting fundamental longevity pathways and maintaining skin health. Future research could focus on identifying the specific bioactive compounds responsible for AMPK activation within the extract and further explore its efficacy and safety through in vivo studies and clinical trials.
Link to the study: https://www.mdpi.com/2079-9284/12/2/57
