Targeting Skin Aging Hallmarks In Vitro: Antioxidant, Anti-Inflammatory, and Anti-Senescence Effects of Phenolic-Rich Extracts from Cistus L. Species

Plant-based extracts are rich sources of phenolic compounds, which may act as skin antiaging mediators. Herein, <i>Cistus albidus</i> L. (Ca), <i>Cistus ladanifer</i> L. subsp. <i>ladanifer</i> (Cl) and <i>Cistus salviifolius</i> L. (Cs) were selected to test whether their phytochemical profile and bioactive potential align to target human skin aging. Hydroethanolic extracts (HEs) were prepared and characterized using infrared vibrational spectroscopy (FTIR-ATR) and liquid chromatography-mass spectrometry (LC-MS). Non-toxic concentrations were screened, and cytoprotective and antioxidant effects were studied in <i>tert</i>-butyl hydroperoxide-stimulated normal human dermal fibroblasts (NHDFs). Lipopolysaccharide-stimulated RAW 264.7 macrophages were used to assess anti-inflammatory activity, the Organization for Economic Co-operation and Development (OECD) Test Guideline No. 439 was used to assess irritant effects, and the anti-senescence potential was assessed in etoposide-stimulated NHDFs. A series of enzymatic inhibition assays was performed. All extracts comprised ellagic acid derivatives, as well as myricetin and quercetin derivatives in Cs and Ca. The HE of Cs was also markedly composed of ligstroside. At non-toxic concentrations, cytoprotective effects were observed in NHDFs. However, only Cs and Cl exhibited significant antioxidant activity in these cells (<i>p</i> < 0.001 and <i>p</i> < 0.0001, respectively). In addition to that, Cl demonstrated highly significant anti-inflammatory (<i>p</i> < 0.0001) and anti-senescence (<i>p</i> < 0.0001) effects. Cs and Cl showed a remarkable potential to inhibit elastase; in addition, Cs also showed anti-hyaluronidase and anti-tyrosinase activities. Meaningfully, Cs and Cl extracts did not exhibit skin irritant effects. The unveiled potential of Cl in skin aging offset highlights the need to elucidate the detailed mechanisms of action, paving the way for the development of skin anti-aging formulations.