We carried out this study to search a new active constituent that had cognitive enhancing activity and low side effects from natural source. We found that the extract of dried root of Polygala tenuifolia Willdenow (BT-11, 10 mg/kg, i.p.) could significantly reverse scopolamine-induced cognitive impairments in rat, using a passive avoidance and a water maze test. We also investigated the effects of BT-11 on neurotoxicity induced by glutamate (Glu) and toxic metabolites of amyloid precursor protein (APP) such as amyloid beta protein (A beta) and C-terminal fragment of APP (CT) in primary cultured neurons of rat. The pretreatment of BT-11 (0.5, 3, and 5 micro g/ml) significantly reduced cell death induced by Glu (1 mM), A beta (10 micro M) and CT105 (10 micro M) in a dose-dependent manner. In addition, BT-11 inhibited acetylcholinesterase (AChE) activity in a dose-dependent and non-competitive manner (IC(50) value; 263.7 micro g/ml). Our novel findings suggest the possibility that this extract may have some protective effects against neuronal death and cognitive impairments in Alzheimer's disease (AD), or other neurodegenerative diseases related to excitotoxicity and central cholinergic dysfunction.