Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats

The effects of (-)-huperzine A, a promising therapeutic agent for Alzheimer 's disease. on learning behavior and on alterations of the cholinergic syst em, the oxygen free radicals and energy metabolites induced by permanent bi lateral Ligation of the common carotid arteries were investigated in rats. Daily oral administration of huperzine A produced a significant improvement of the deficit in the learning of the water maze task, beginning 28 days a fter ischemia, correlating to about 33-40% inhibition of acetyl-cholinester ase activity in cortex and hippocampus. Huperzine A significantly restored the decrease in choline acetyltransferase activity in hippocampus and signi ficantly reduced the increases in superoxide dismutase, lipid peroxide, lac tate and glucose to their normal levels. The present findings demonstrate t hat the improvement by huperzine A of the cognitive dysfunction in the late phase in chronically hypoperfused rats is due to its effects, not only on the cholinergic system, but also on the oxygen free radical system and ener gy metabolism. Out results strongly suggest that huperzine A has therapeuti c potential for the treatment of dementia caused by cholinergic dysfunction and/or decrease of cerebral blood flow. (C) 2000 Elsevier Science B.V. All rights reserved.