Exploring the Multitarget Pharmacological Potential of Halogeton sativus Secondary Metabolites: An Integrated Experimental and Computational Approach.

This study offers an in-depth analysis of Halogeton sativus, traditionally consumed in the Mediterranean region. Phytochemical investigation of crude extracts allowed the isolation and spectroscopic identification of 15 secondary metabolites. α-Amylase inhibitory and anti-inflammatory activities were determined via the caraway iodine method, heat-induced lysis, and denaturation inhibition assays, respectively. The antimicrobial activity was tested using a disc diffusion method, and the antioxidant effects were assessed by six methods. The ethyl acetate extract (HS-EtOAc) showed a stronger α-amylase inhibitory effect (IC50 = 28.70 µg/mL) compared to the reference drug, while the HS-BuOH exerted strong antioxidant activities in CUPRAC (A0.5 = 3.75 µg/mL) and hydrogen peroxide radical scavenging assays. Additionally, all extracts protected erythrocyte membranes, prevented protein denaturation, and displayed moderate antimicrobial effects. To elucidate the mechanism of action behind these observed bioactivities, drug-likeness, ADMET properties, and molecular docking (α-amylase, IL-1β, and DNA gyrase) of the isolates were performed. The results revealed high binding affinities associated with promising pharmacokinetic and safety profiles. Furthermore, the stability of the resulting ligand-target complexes was validated through 100 ns molecular dynamics simulations, with MM-PBSA calculations providing quantitative binding free energies. These results underscore the potential of H. sativus as a valuable source of potential therapeutic agents.