Pharmacological studies on the leaves, flowers, seeds, and bark of Nyctanthes arbor-tristis Linn have confirmed their traditional therapeutic roles in managing diverse health conditions. This research assessed the anti-inflammatory capabilities of 26 plant-derived compounds through molecular docking with AutoDock 4.2, supplemented by Molecular Dynamics Simulations using GROMACS. SwissADME was employed to analyze ADME (absorption, distribution, metabolism, and excretion) profiles. Among these, Arb_E and Beta-sito exhibited robust binding interactions with targets including COX-1, COX-2, PDE4, PDE7, IL-17A, IL-17D, TNF-α, IL-1β, prostaglandin E2, and prostaglandin F synthase. The standard inhibitor celecoxib showed a binding energy of −9.29 kcal/mol, whereas Arb_E stood out with the highest affinity (docking energy: −10.26 kcal/mol). Beta_sito also demonstrated substantial binding with −8.86 kcal/mol against COX-2. In simulations of COX-2 complexed with Arb_E or celecoxib, RMSD values stayed within 0.15 to 0.25 nm, confirming complex stability over the entire duration. Additionally, MM-PBSA calculations indicated that Arb_E's interaction with COX-2 had the most favorable binding energy at −277.602 kJ/mol. Both compounds presented desirable physicochemical properties and drug-likeness in ADME evaluations, suggesting strong therapeutic promise. Hence, these plant constituents may represent viable candidates for anti-inflammatory therapy and require further validation through in vitro and in vivo testing to advance new drug development.
