In Silico Investigation of the Anti-Inflammatory Activity of Some Diarylheptanoids

Purpose: The search for potentially non-toxic and efficacious anti-inflammatory agents has been of keen interest among researchers due to the side effects of existing anti-inflammatory agents, making their long-term use unsuitable. This study aimed to explore the mechanisms of the anti-inflammatory activity of some diarylheptanoids. Methods: We performed molecular docking and MM/GBSA binding free energy calculations to assess the binding affinity of selected diarylheptanoids against nuclear factor-kB (PDB ID: 1NFK) and COX-2 (PDB ID: 3LN1). The stability of the lead complexes was evaluated using molecular dynamics simulations for 200ns. The SwissADME web tool and HyperChem 8.0 were used to predict the physicochemical and pharmacokinetic properties. Results: The results revealed that platyphylloside and hirsutenone were potential NF-kB inhibitors with docking scores of -4.76 and -4.48 Kcal/mol; and binding free energies of -15.84 and -31.17 Kcal/mol. Furthermore, hirsutenone and yakuchinone were identified as potential inhibitors of cyclooxygenase 2 enzyme with docking scores of -11.81 and -10.63 Kcal/mol; and binding free energies of -54.72 and -45.95 Kcal/mol. The types of interactions between the diarylheptanoids’ atoms and amino acid residues in the target protein active site were the same as those of the reference inhibitors; dexamethasone for NF-kB, and Celecoxib for COX-2, thus further confirming their potential as NF-kB and COX-2 inhibitors. Conclusion: Inhibition of NF-kB remains a promising strategy in the treatment of inflammation, and hirsutenone has been identified as a potentially safe and effective anti-inflammatory agent for treating chronic inflammatory conditions, whose anti-inflammatory properties may include both NF-kB and cyclooxygenase 2 inhibition.