Exploring Anti-Aging Potential of Flavonoids from Muntingia calabura Fruit Extract: LC-ESI/MS, Network Pharmacology, and Molecular Validation

Muntingia calabura L. has been reported to possess diverse pharmacological effects, with flavonoid derivatives recognized as the main bioactive constituents. This study aimed to identify flavonoids from M. calabura fruit extract and to explore their pharmacological potential as anti-aging agents targeting key proteins through a network pharmacology approach and in silico analyses. The research was conducted in several stages, including maceration extraction and identification of flavonoid compounds from the ethanol extract of M. calabura fruit. The identified compounds were subsequently evaluated for physicochemical properties and skin permeability using web-based tools. Compounds meeting these criteria were further analyzed through network pharmacology, molecular docking, and molecular dynamics simulations. A total of 41 compounds were identified, including 36 flavonoid derivatives. Among them, 6-hydroxy-7-methoxy-2-(2-phenylethyl)-chromone (compound 16) demonstrated strong multi-target interactions with aging-related proteins, including collagenase, gelatinase, elastase, and tyrosinase. Physicochemical and skin permeability evaluations indicated that 38 compounds were suitable for further analysis, while network pharmacology linked 19 compounds to aging-related proteins, particularly matrix metalloproteinases (MMPs) and tyrosinase (TYR). Docking studies revealed that compound 16 exhibited binding affinities of –8.65 kcal/mol (collagenase), –8.91 kcal/mol (gelatinase), –7.26 kcal/mol (elastase), and –1.31 kcal/mol (tyrosinase). Molecular dynamics simulations confirmed the stability of these interactions. Collectively, these findings suggest that the ethanol extract of M. calabura fruit may exert anti-aging effects, supported by the presence of stable, multi-target flavonoid derivatives, making it a promising candidate for further research and development.