Deciphering the Phytochemical Profile of an Alpine Rose (Rhododendron ferrugineum L.) Leaf Extract for a Better Understanding of Its Senolytic and Skin-Rejuvenation Effects

Abstract

Rhododendron ferrugineum, commonly named Alpine rose, is an emblematic medicinal plant of European mountains. In this study, the chemical profile of a glycerol/water extract developed from this plant as a cosmetic ingredient is investigated to understand the extract constituent(s) that could mostly contribute to its senolytic activity and skin-rejuvenation effects. For this purpose, the dereplication method “CARAMEL”, which combines Centrifugal Partition Chromatography to Nuclear Magnetic Resonance data interpretation, was directly applied to the hydro-glycerinated extract, leading to the unambiguous identification of fourteen Alpine rose metabolites, despite the strong presence of the heavy solvent glycerol. Flavonoids derived from taxifolin, quercetin, and (+)-catechin were identified as significant constituents of the extract, followed by flavanones, orcinol derivatives, phloroacetophenone, and phenolic acids, as well as the pentacyclic triterpene lupeol. Given that senolytic molecules are known to selectively induce the death of senescent cells without affecting healthy proliferating cells, which can be achieved by the selective inhibition or downregulation of the anti-apoptotic Bcl-2 protein, and considering the well-recognized pro-apoptotic activity of hyperoside, taxifolin, naringenin and farrerol, the senolytic activity of the glycerol/water Alpine rose extract can be explained by the abundance of flavonoids present in the extract.