Prolonged effects of poly(lactic-co-glycolic acid) microsphere-containing huperzine A on mouse memory dysfunction induced by scopolamine

Abstract

Huperzine A is an anticholinesterase and cognitive enhancer, which is able to alleviate the symptoms of memory dysfunction in the mouse. The fast metabolization rate and narrow therapeutic spectrum makes it unfit for clinical use. Poly(lactic-co-glycolic acid) microsphere as delivery system effectively maintains the blood concentration of huperzine A by a slow-release effect over a long time. In the present article, we investigated the prolonged protective effect of microsphere-containing huperzine A on memory dysfunction induced by scopolamine. Spectrophotometric assay was used to determine the activity of acetylcholinesterase (AChE) and passive avoidance tests to evaluate memory performance. The results show that a bolus dose of microsphere-containing huperzine A (at a dose of 300 μg/kg or 600 μg/kg) administered intramuscularly can effectively maintain drug activity and significantly decrease the activity of AChE from day 3 to 14, the strongest effect seen on day 3 and 7. Accompanying the reduction of the activity of AChE, microsphere-containing huperzine A (300 μg/kg or 600 μg/kg) remarkably increased transfer latency time and no transfer response on the second trial through mitigating the memory impairments induced by scopolamine as compared to the scopolamine model group. Microsphere-containing huperzine A showed cognitive enhancing properties and anticholinesterase activity and may thus be a candidate for treatment of memory impairment. © 2007 The Authors Journal compilation © 2007 Nordic Pharmacological Society.