In vitro and in silico ROS and NO inhibition by grains of Selim (Xylopia aethiopica) extract and its phytoconstituents

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Xylopia aethiopica is a medicinal and food plant of the Annonaceae family, used as a spice for flavouring foods and beverages. The anti-inflammatory potential of X. aethiopica extract was evaluated in vitro while its phytoconstituents were evaluated through molecular docking against two key pro-inflammatory targets, cyclooxygenase-2 (COX-2) and tumour necrosis factor-alpha (TNF-α), using GNINA v1.0.3, a deep-learning-augmented docking framework. X. aethiopica extract had low inhibition ( p < 0.05) of nitric oxide (NO) with an IC 50 of 79.0±1.3 µg/mL compared to the standard L-NMMA which showed an IC 50 value of 24.2±0.8 µg/mL. Oxidative burst (ROS) inhibition was good with an IC 50 value of 16.5±2.1 µg/mL compared to ibuprofen (IC 50 = 11.2±1.9 µg/mL). A total of 43 phytoconstituents representing alkaloids, diterpenes, triterpenes, flavonoids, steroids, and phenolics were docked against the rofecoxib-bound form of COX-2 (PDB: 5KIR ) and the SPD304-bound form of TNF-α (PDB: 2AZ5 ), with ibuprofen as the reference anti-inflammatory compound. Against COX-2, ten compounds exceeded ibuprofen (reference: −7.61 kcal/mol), with trans-tiliroside (−12.48 kcal/mol), liriodenine (−10.22 kcal/mol), oxonantenine (−9.93 kcal/mol), and lanuginosine (−9.65 kcal/mol) as the strongest binders. Against TNF-α, 37 of 38 natural products surpassed ibuprofen (reference: −5.95 kcal/mol). The aporphine alkaloids liriodenine (COX-2: −10.22, TNF-α: −8.14 kcal/mol), oxonantenine (COX-2: −9.93, TNF-α: −7.99 kcal/mol), and lanuginosine (COX-2: −9.65, TNF-α: −8.28 kcal/mol) were the top three confirmed dual-target leads. Interaction profiling by BIOVIA Discovery Studio revealed that binding at COX-2 is anchored by a π-cation interaction with ARG120, consistent with competitive displacement of arachidonic acid, while TYR59 pi-pi stacking constitutes the universal pharmacophoric anchor at the TNF-α subunit interface across all top leads. These findings provide a molecular basis for the reported anti-inflammatory activity of X. aethiopica extracts.