A bioassay-guided isolation on the plant Zanthoxylum armatum DC yielded compounds tambulin (1), and prudomestin (2), from ethyl acetate fraction which showed the highest ROS inhibiting activity (IC50 = 17.8 ± 1.1 µg/mL). Structure elucidation of pure compounds was done using mass and NMR spectroscopic techniques. Compounds 1 and 2 revealed potent ROS inhibition with IC50 = 7.5 ± 0.3 and 1.5 ± 0.3 µg/mL, respectively, as compared to standard ibuprofen (IC50 = 11.2 ± 1.9 µg/mL). Likewise, both compounds 1 and 2 showed potent antioxidant activity with IC50 = 32.65 ± 0.31 and 26.96 ± 0.19 µg/mL, respectively. In vitro studies were supported by molecular docking and drug-likeliness properties. In silico studies of 1 and 2 with cyclooxygenase-2 (COX-2) showed perfect binding affinity with binding energies of -8.4 and -8.6 kcal/mol, respectively, comparable to standard ibuprofen (-7.7 kcal/mol). Drug likeness and ADMET showed higher gastrointestinal absorption of 1 and 2 and no toxic impact.
Keywords: Anti-inflammatory; Zanthoxylum armatum DC; antioxidant; flavonoids; molecular docking; reactive oxygen species.