Multi-Target Bioactivity of Dittrichia viscosa Polyphenols: HPLC-ESI-MS Profiling, Antimicrobial Mechanisms, and...

Background/Objectives:Dittrichia viscosa (L.) W. Greuter (Asteraceae) is a Mediterranean medicinal plant whose polar phenolic fraction remains insufficiently characterized. This study aimed to characterize the phenolic composition and evaluate the antioxidant, antimicrobial, and mechanistic bioactivity of aqueous and methanolic leaf extracts collected from the Rmilate Forest in Tangier, northern Morocco. Methods: Extracts were characterized by ICP-AES for elemental content and by HPLC-PDA-ESI-MS for phenolic annotation, and total phenolic, flavonoid, and tannin contents were quantified. Antioxidant capacity was assessed using DPPH, ABTS, FRAP, and ORAC assays. Antibacterial activity was evaluated against four reference strains, with time-kill kinetics and membrane integrity assays used to probe the mechanism of action, and antifungal activity was tested against dermatophytic and phytopathogenic fungi. Molecular docking against four bacterial, fungal, and antioxidant enzyme targets and ProTox-3 toxicity prediction were also performed. Results: ICP-AES revealed high concentrations of calcium (12,476.75 mg/kg) and potassium (29,699 mg/kg). The methanolic extract showed higher total phenolic (55.05 mg GAE/g), flavonoid (84.18 mg QE/g), and tannin (262.1 mg TAE/g) contents and superior antioxidant activity (DPPH IC₅₀: 0.090 mg/mL). Twelve phenolic compounds were tentatively annotated, including caffeic acid, caffeoylquinic acid derivatives, and quercetin/kaempferol glycosides. Antibacterial activity (MIC: 0.25-1 mg/mL) was consistent with cell envelope disruption, and up to 88% mycelial inhibition was achieved against Trichophyton rubrum. Docking ranked kaempferol-3-O-pentoside (-10.3 kcal/mol) among the top-scoring ligands, and the top compounds were assigned to toxicity class 5. Conclusions:D. viscosa is a promising source of bioactive phenolics for pharmaceutical and agrochemical development.