Robustanic acid as a glutaminase and Na+, K+-ATPase inhibitor from leaves of Eucalyptus globulus.

Abstract

This study was to compare glutaminase and Na+, K+-ATPase inhibitory activities of 20 herbal extracts and investigate the isolation, structural elucidation and those inhibitory activities of three triterpenes from the selected extract of Eucalyptus globulus Labill. Three triterpenes, ursolic acid (1), robustanic acid (2) and ursolic acid lactone (3), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC50 values of 1-3 and the control compound against glutaminase, 6-diazo-5-oxo-l-norleucine (DON), were 443 μM, 334 μM, 963 μM and 134 μM, respectively. The IC50 values of 1, 2 and the control compound against Na+, K+-ATPase and ouabain, were 180 μM, 56 μM and 0.5 μM, respectively. Compounds 1 and 2 may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting glutaminase and Na+, K+-ATPase. This is the first report on glutaminase and Na+, K+-ATPase inhibitory activities of 2.