Metabolite Profiling and Skin Anti-Aging Potential of Astragalus sarcocolla: Antioxidant, Enzyme Inhibitory, and Computational Insights

The study evaluated the skin anti-aging activity of Astragalus sarcocolla leaves extract (ASE) by assessing its antioxidant and inhibitory effect activity on matrix metalloproteinase (MMP), collagenase, elastase, hyaluronidase, and tyrosinase in relation to its chemical composition. Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) identified 27 metabolites (15 flavonoids, 8 phenolic acids and their derivatives, and 4 coumarins). ASE showed strong antioxidant capacity in DPPH (IC₅₀ value of 26.05 µg/mL) and FRAP (2433 µM FeSO₄/g extract) assays. The extract inhibited MMP-1 and MMP-9 in a concentration-dependent manner and suppressed collagenase, elastase, hyaluronidase, and tyrosinase activities (IC₅₀ = 35.038, 40.748, 61.389, and 30.980 µg/mL, respectively). A network pharmacology study was conducted to uncover the mechanisms responsible for skin anti-aging effects, and molecular docking further evaluated interactions of key metabolites with hub targets. Twenty-one bioactive metabolites, selected based on oral bioavailability and drug-likeness, highlighted cinnamic acid, acacetin, luteolin, kaempferol, and apigenin as key compounds. MMP-9, ESR1, PTGS-2, and EGFR were identified as main targets. Docking studies revealed that acacetin and apigenin have stronger binding affinities to MMP-9, PTGS-2, and EGFR than other constituents. These findings suggest that ASE may serve as a natural multi-target skin anti-aging remedy with potential cosmetic applications.