Integrated LC‐MS/MS Profiling, In Vitro Antioxidant, and Anti‐Inflammatory Evaluation, Molecular Docking, and Molecular Dynamics Simulation of Bioactive Compounds from <i>Dittrichia Viscosa</i>

Abstract

ABSTRACT This study investigates the hydroethanolic leaf extract of Dittrichia viscosa (L.) Greuter, collected from northeastern Algeria, a plant widely recognized in Mediterranean traditional medicine for its therapeutic properties. LC‐MS/MS analysis tentatively identified eleven major bioactive compounds, including folic acid, β‐carotene, thymol, oleanolic acid, resveratrol, riboflavin, rutin, sinapic acid, ferulic acid, naringenin, and 4‐methoxybenzoic acid. The antioxidant activity was evaluated using DPPH and FRAP assays, revealing strong reducing power with IC 50 values of 0.2808 mg/mL (95% CI: 0.19–0.3715) and 0.5314 mg/mL, respectively. Anti‐inflammatory activity assessed by the protein denaturation assay showed dose‐dependent inhibition with an IC 50 of 0.0780 mg/mL, comparable to diclofenac (IC 50 = 0.1021 mg/mL) under in vitro conditions. Molecular docking demonstrated that naringenin exhibits strong binding affinity toward COX‐2, while rutin shows favorable interaction with Keap1, supporting their anti‐inflammatory and antioxidant roles. Molecular dynamics simulations over 100 ns confirmed the stability of both ligand–protein complexes, and MM‐PBSA calculations further supported these findings by revealing favorable and consistent binding energies. Overall, these results highlight Dittrichia viscosa as a promising natural source of antioxidant and anti‐inflammatory agents.