Asiatic acid derivatives enhance cognitive performance partly by improving acetylcholine synthesis

Thirty-six semi-synthesized derivatives of asiatic acid were examined to determine if they had cognitive-enhancing activity in a passive avoidance test. Among the compounds tested, AS-2, AS-2-9-006 and AS-9-006 significantly alleviated scopolamine-induced memory impairment at doses of 1 and 10 mg kg(-1). Furthermore, AS-2 and AS-2-9-006 (1 mg kg(-1) administered four times daily) enhanced cognitive performance as determined in a water maze test. These three asiatic acid derivatives did not show any significant effect on the learning process in active avoidance tests. AS-2, AS-2-9-006 and AS-9-006 enhanced cholineacetyltransferase activity in a cholinergic neuroblastoma cell line, S-20Y, in-vitro. Therefore, AS-2, AS-2-9-006 and AS-9-006 may have therapeutic value in alleviating certain memory impairment observed in dementia.