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

Abstract

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.