Astragalus membranaceus sprouts and their unique constituents regulate reactive oxygen species production, inflammation-related senescence-associated secretory phenotype components, and extracellular matrix in fibroblasts.

Aging involves a gradual decline in physiological functions and increased susceptibility to damage and disease. Suppressing reactive oxygen species (ROS) production and inflammatory responses is critical for delaying age-related cellular decline. Astragalus membranaceus is one of the important health functional foods worldwide due to its health benefits, including antioxidant and immunomodulatory properties. While the root is the most commonly utilized part, other plant parts remain largely unexplored despite their potential benefits. This study investigated that A. membranaceus sprouts and their unique constituents could regulate ROS production, inflammation-related senescence-associated secretory phenotype components, and extracellular matrix in fibroblasts. Sprouts showed better biological activities than roots; molecular networking analysis revealed 15 sprout-specific flavonoid-3-O-glycosides, including one new natural and eight previously unreported ones (1-9), as key metabolites underlying this result. Astraflavonol H (8) exhibited potent bioactivity. Molecular target analysis of the compound using ligand-based in silico tools revealed the involvement of the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Western blotting analysis revealed KEAP1 downregulation and NRF2 and heme oxygenase-1 upregulation. Molecular docking indicated the Kelch domain of KEAP1 as the binding site. Astraflavonol H increased NRF2 protein stability and attenuated tumor necrosis factor-α-induced Janus-activated kinase and signal transducer and activator of transcription-1 phosphorylation. Overall, this study highlights the potential of A. membranaceus sprouts and their components as anti-aging foods.