Abstract
The effects of (-)-huperzine A, a promising therapeutic agent for Alzheimer's disease, on learning behavior and on alterations of the cholinergic system, the oxygen free radicals and energy metabolites induced by permanent bilateral 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 after ischemia, correlating to about 33-40% inhibition of acetylcholinesterase activity in cortex and hippocampus. Huperzine A significantly restored the decrease in choline acetyltransferase activity in hippocampus and significantly reduced the increases in superoxide dismutase, lipid peroxide, lactate and glucose to their normal levels. The present findings demonstrate that 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 energy metabolism. Our results strongly suggest that huperzine A has therapeutic potential for the treatment of dementia caused by cholinergic dysfunction and/or decrease of cerebral blood flow. (C) 2000 Elsevier Science B.V.
| Original language | English |
|---|---|
| Pages (from-to) | 65-72 |
| Number of pages | 8 |
| Journal | European Journal of Pharmacology |
| Volume | 398 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 9 Jun 2000 |
| Externally published | Yes |
Keywords
- (-)-Huperzine A
- Acetylcholinesterase
- Alzheimer's disease
- Cerebral ischemia
- Cholinesterase inhibitor
- Free radical
- Learning
- Memory
- Morris water maze
ASJC Scopus subject areas
- Pharmacology