Racha Lydia Bouchouka, Farida Larit, Zahia Kabouche, Marlène Debiossat, Laurent Riou, Catherine Ghezzi, Francisco León, Ahmed Kabouche
Asphodelus tenuifolius Cav. (Asphodelaceae) is traditionally used in North African ethnomedicine for inflammatory and oxidative stress-related disorders. In this study, the hydroethanolic root extract was investigated by LC-HRMS/MS, leading to the identification of 58 metabolites, mainly flavonoids, anthraquinones, and cinnamic acid derivatives. Major constituents included luteolin, emodin, luteolin-7-O-β-D-glucoside, subaphyllin (N-trans-feruloylputrescine), and N-trans-feruloyltyramine. The extract showed moderate antiproliferative activity against MDA-MB-231 and PC-3 cells, while flow cytometry revealed pronounced apoptosis induction (up to 85%) and significant G0/G1 cell-cycle arrest. Molecular docking and target prediction suggested multitarget modulation of ERα, AR, AKT1, CDK2, and BCL-2, particularly by aglycone metabolites. ADMET analysis indicated favorable drug-likeness and safety profiles. These findings provide the first mechanistic evidence supporting the multitarget anticancer potential of A. tenuifolius roots and highlight their value as a source of bioactive anticancer scaffolds.