Artemisia roxburghiana is used in traditional medicine for treating various diseases including diabetes. The present study was designed to evaluate the antidiabetic potential of active constituents by using protein tyrosine phosphatase 1B (PTP1B) as a validated target for management of diabetes. Various compounds were isolated as active principles from the crude methanolic extract of aerial parts of A. roxburghiana. All compounds were screened for PTP1B inhibitory activity. Molecular docking simulations were performed to investigate the mechanism behind PTP1B inhibition of the isolated compound and positive control, ursolic acid. Betulinic acid, betulin and taraxeryl acetate were the active PTP1B principles with IC 50 values 3.49 ± 0.02, 4.17 ± 0.03 and 87.52 ± 0.03 mM, respectively. Molecular docking studies showed significant molecular interactions of the triterpene inhibitors with Gly220, Cys215, Gly218 and Asp48 inside the active site of PTP1B. The antidiabetic activity of A. roxburghiana could be attributed due to PTP1B inhibition by its triterpene constituents, betulin, betulinic acid and taraxeryl acetate. Computational insights of this study revealed that the C-3 and C-17 positions of the compounds needs extensive optimization for the development of new lead compounds.

Cycloxygenase inhibitors are one of the main class of therapeutic agents for management of inflammation. New COX inhibitors are discovered from natural and synthetic sources. In the current investigation taraxerol acetate have been discovered as a new COX inhibitor. Taraxerol acetate showed considerable inhibitory activity against both COX-1 (IC50: 116.3 ± 0.03 μM) and COX-2 (IC50: 94.7 ± 0.02 μM) enzymes using in-vitro enzyme inhibition assay. Molecular docking revealed significant interactions of taraxerol acetate with the important amino acid residues surrounding the inhibitor in binding pocket of COX-2 enzyme. This study indicate potential of taraxerol acetate to be further explored and modified as a new lead compound for better management of inflammatory conditions via targeting COX enzymes. Article Info