Inhibitory effect of ursolic acid purified from Origanum majorana L. on the acetylcholinesterase

We screened 139 herbal spices in seal ch of the acetylcholinesterase (AChE) inhibitor from natural resources. AChE inhibitors, which enhance cholinerg ic transmission by reducing the enzymatic degradation of acetylcholine, al e the only source of compound currently approved for the treatment of Alzhe imer's Disease (AD), Among these herbs, edible plants and spices, the ethan ol extract fi om Origanum majorana L, showed the highest inhibitory effect on AChE in vitro. By sequential fractionation of Origanum majorana L,, the active component was finally identified as ursolic acid (3 beta -Hydroxyurs -12-en-28-oic acid), The ursolic acid of Origanum majorana L, inhibited ACh E activity in a dose-dependent and competitive/non-competitive type. The K- i value (representing the affinity of the enzyme and inhibitor) of Origanum majorana L, ursolic acid was 6 pM, and that of tacrine was 0.4 nM, The con centration required for 50% enzyme inhibition of the active component (IC50 value) was 7.5 nM, and that of tacrine was 1 nM, This study demonstrated t hat the ursolic acid of Origanum majorana L, appeared Co be a potent AChE i nhibitor in Alzheimer's Disease.