Abstract:
While screening extracts of natural products in search of anticholinesterase
activity, we found that a total methanolic extract of the tuber of
Corydalis ternata (Papaveraceae) showed significant inhibitory effects
on acetylcholinesterase. Further fractionation of this extract using acetylcholinesterase
inhibition as the parameter screened resulted in the isolation and purification
of an alkaloid, protopine. Protopine inhibited acetylcholinesterase activity
in a dose-dependent manner. The concentration required for 50 % inhibition
was 50 μM. The anti-acetylcholinesterase activity of protopine
was specific, reversible and competitive in manner. Furthermore, when mice
were pretreated with protopine, the alkaloid significantly alleviated scopolamine-induced
memory impairment. In fact, protopine had an efficacy almost identical to
that of velnacrine, a tacrine derivative developed by a major drug manufacturer
to treat Alzheimer's disease, at an identical therapeutic concentration. We
suggest, therefore, that protopine has both anti-acetylcholinesterase and
antiamnesic properties that may ultimately hold significant therapeutic value
in alleviating certain memory impairments observed in dementia.
Key words:
Corydalis ternata
- Papaveraceae - protopine - reversible AChE inhibitor - scopolamine-induced memory impairment - dementia - tacrine
