Ethnopharmacological and Antiaging Evaluation of Salvia cadmica: Modulation of MMP1/MMP3 and Collagen in Oxidative Stress-Induced Senescence.

Salvia cadmica, an Anatolian endemic species traditionally used for wound healing and inflammation, has been scarcely investigated for its anti-aging potential. In this study, the aqueous-ethanol extract of S. cadmica was evaluated for its antioxidant, cytoprotective, and anti-senescence effects using in vitro and in silico approaches. LC-ESI-MS/MS analysis identified rosmarinic acid (3447 µg/g), luteolin 7-glucoside (767 µg/g), and luteolin (586 µg/g) as major constituents. The extract exhibited strong antioxidant capacity, particularly in the phosphomolybdenum assay (713.51 mg TEs/g), and showed notable radical scavenging activity in ABTS (140.00 mg TEs/g) and DPPH (99.20 mg TEs/g) assays. In H2O2-induced senescent human dermal fibroblasts (HDFa), pre-treatment with the extract significantly reduced senescence-associated β-galactosidase positivity from 97.15% to 49.12% and improved cell viability. The extract downregulated MMP1 and MMP3 mRNA expression (0.51- and 0.66-fold, respectively) while markedly upregulating COL1A1 expression (7.48-fold). Molecular docking and MM/GBSA analyses revealed that luteolin 7-glucoside showed high binding affinities toward MMP1 and MMP3 (ΔGdocking = -9.06 and -9.86 kcal/mol; ΔGMM/GBSA = -37.21 and -50.22 kcal/mol, respectively). In silico ADMET predictions supported a favorable dermal safety profile. Overall, S. cadmica represents a promising natural source of bioactive compounds with antioxidant and anti-aging potential relevant to skin aging prevention.