Chemical profiling and biological activities of <i>Athamanta sicula</i> L. Aerial parts extracts: <i>in vitro</i> and in <i>silico</i> approaches

Athamanta sicula, traditionally used in infusions for its diuretic effects, was investigated for its chemical composition and biological activities through in vitro and in silico approaches. Following maceration, the extracts were fractionated with solvents ranging from nonpolar to polar, including diethyl ether (ASEE), ethyl acetate (ASAE), and n-butanol (ASBE). Chemical profiling identified vanillic acid as the major compound in all extracts: ASEE (2.46 ± 0.03 mg/g), ASAE (1.76 ± 0.03 mg/g), and ASBE (1.57 ± 0.02 mg/g). All samples demonstrated antioxidant activity, surpassing standard compounds (BHA and Ascorbic acid) in reducing power. Enzyme inhibition measured by half maximal inhibitory concentration (IC50) revealed that extracts derived from ASBE and ASEE exhibited stronger α-amylase inhibition (IC50 = 683 ± 23 and 747 ± 29 µg/mL, respectively) than acarbose (IC50 = 3,650 ± 10 µg/mL). Pancreatic lipase inhibition was significant only in ASAE (IC50 = 10.14 ± 0.93 µg/mL), outperforming orlistat (IC50 = 25.07 ± 0.48 µg/mL). All extracts inhibited protein denaturation more effectively than diclofenac, with ASBE showing the highest inhibition (88.89%). Additionally, moderate cytotoxic effects were observed against breast cancer cell lines (MCF-7 and MDA-MB-231). Molecular modeling suggested a synergistic interaction of compounds in ASAE with pancreatic lipase, while ADME predictions indicated favorable oral bioavailability for most phenolic acids except rutin. The observed bioactivities emphasize the medicinal value of A. sicula, supporting its potential role as a natural additive in food preservation and pharmaceutical formulation.