Élucidation des mécanismes moléculaires de l’activité anti-inflammatoire de l’huile essentielle de Dittrichia viscosa: étude multi-cibles sur la cascade de l’acide arachidonique

This study aims to provide a mechanistic interpretation of the traditionally reported anti-inflammatory properties of Dittrichia viscosa (L.) Greuter. Using an in silico approach, we investigated the inhibitory potential of its leaf essential oil constituents against three key enzymes of the arachidonic acid cascade: cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and cytosolic phospholipase A₂ (cPLA₂).Molecular docking simulations were performed using MOE software. The molecular database was constructed based on the chemical profiles of D. viscosa essential oils from ten distinct Algerian populations. The docking protocol was validated using co-crystallized reference inhibitors for each human enzyme target. Affinity was evaluated through S-scores (kcal/mol) and detailed analysis of ligand-residue interactions within the catalytic sites.The results revealed that several major sesquiterpenes exhibit significant binding affinities comparable to or exceeding those of reference NSAIDs. (E)-Nerolidol demonstrated the highest affinity for COX-2 (-7.25 kcal/mol), establishing key interactions with Arg120 and Tyr385. For 5-LOX, farnesylacetone emerged as the most potent ligand (-6.02 kcal/mol), uniquely coordinating with the catalytic iron (Fe²⁺). Regarding cPLA₂, farnesylacetone (-5.30 kcal/mol) and α-bisabolol (-5.21 kcal/mol) were identified as the most effective natural inhibitors, mimicking synthetic standards by interacting with critical residues such as LYS32 and ASN64.