Glutaminase inhibitory activities of pentacyclic triterpenes isolated from Thymus vulgaris L.

Glutaminase is an important target that is often over expressed in neurodegenerative and　lifestyle related diseases but few effective inhibitors of this enzyme have yet reached clinical trials. Ursolic acid (1), betulinic acid (2) and oleanolic acid (3), three pentacyclic triterpene acids, have been isolated from the leaves of Thymus vulgaris L. Enzyme inhibition experiments demonstrated their inhibitory effects against glutaminase activity. Compound 2 significantly inhibited the glutaminase activity with IC50 of 0.31 mM, stronger than the positive control 6-diazo-5-oxo-L-norleucine (DON) with IC50 of 0.57 mM. Compound 2 may serve as a potential lead compound for the prevention and treatment of neurodegenerative diseases and lifestyle related diseases by targeting glutaminase. This is the first report on glutaminase inhibitory activities of 1-3 isolated from T. vulgaris L.