Novel Anticholinesterase and Antiamnesic Activities of Dehydroevodiamine, a Constituent ofEvodia rutaecarpa

Abstract

To find a new compound with antiamnesic activity, we screened 29 natural products for their abilities to inhibit acetylcholinesterase and reverse scopolamine-induced amnesia. Among the plants tested Evodia rutaecarpa Bentham showed a strong inhibitory effect on acetylcholinesterase in vitro and an anti-amnesic effect in vivo. By sequential fractionation of E. rutaecarpa, the active component was finally identified as dehydroevodiamine hydrochloride (DHED). DHED inhibited acetylcholinesterase activity in a dose-dependent and non-competitive manner. The IC50 value of DHED is 37.8 microM. A single administration of DHED to rats (6.25 mg/kg) significantly reversed the scopolamine-induced memory impairment in a passive avoidance test. The antiamnesic effect of DHED was more potent than that of tacrine which is the only drug for Alzheimer's disease approved by FDA. This potent antiamnesic effect of DHED was thought to be due to the combined effects of acetylcholinesterase inhibition and the known cerebral blood flow enhancement. These results indicate that DHED has novel anti-cholinesterase and antiamnesic activities and might have therapeutic potential in various disorders including Alzheimer's disease.

Acetylcholinesterase Inhibition by Flavonoids from Agrimonia pilosa

“…The present study also confirms that these compounds have significant anticholinesterase activity. Particularly quercetin (4) was twice as active against AChE than DHED, which showed more in vivo antiamnesic activty than the clinically useful tacrine [16] and thus, quercetin or its derivatives might have the therapeutic potential for the treatment in Alzheimer's disease. …”

“…These flavonoids are less effective than the clinically useful tacrine (IC 50 = 0.1 μM) and berberine (IC 50 = 0.7 μM). However, tiliroside 1 and quercetin 4 showed higher AChE ihhibitory activity (IC 50 ) than dehydroevodiamine hydrochloride [16].…”

Effects of Oleamide on Choline Acetyltransferase and Cognitive Activities

“…13) Treatment with SCOP (1 mg W kg), a muscarinic receptor blocker, signiˆcant-ly shortened the latency time (31z decrease in stepthrough latency) in the retention trial (Fig. 5).…”

Anti-Alzheimer and Antioxidant Activities of Coptidis Rhizoma Alkaloids

“…[20][21][22][23] In particular, Coptidis Rhizoma and its isolated alkaloids have been reported to exhibit cognitive-en- 24) anti-depressing, 25) and cholinesterase-inhibitory effects. 26,27) Although much research has been conducted considering the anti-AD and neuroprotective effects of Coptidis Rhizoma and its alkaloids, 28,29) the relationship between individual alkaloid structure and anti-AD effects, as well as its relevance to antioxidant effects, remain limited. Furthermore, protoberberine alkaloids with relatively low molecular weight and high lipophilicity are supposed to meet the requirements of promising therapeutic drugs for AD.…”