Influence Of Various Doses Of The Combinations Of β-asarone And Eugenol In Acorus Tatarinowii On Learning-Memory Ability In Dementia Model Rats Induced By Ibotenic Acid

ObjectivesTo observe the influence of various doses of combination of β-asarone and eugenol in Acorus Tatarinowii with the ratio of4:1on learning-memory ability in Alzheimer’s Disease(AD) model rats induced by Ibotenic Acid.Methods119rats were randomly divided into6groups:sham operation group, Scop model group, Donepezil hydrochloride group, and low dose, middle dose and high dose of combination of β-asarone and eugenol. Ibotenic acid was injected into the bilateral NBM to establish the AD model in rats, Morris water maze test was adopted to observe the changes in learning-memory ability. The activity of acetylcholinesterase (AChE) in cerebral cortex were measured. The expressions of Bax and Smad2were detected by immunohistochemisty. Apoptotic cells were detected by Tunel.(1) Morris’ water maze testCompared with sham operation group, rats in model group showed significant prolonging escape latency in last three days in place navigation test(P<0.01). The escape latency in last three days in Donepezil hydrochloride group and high dose group were significantly decreased than that in model group (P<0.05). The escape latency of the rats in middle dose group and low dose group showed no significant change in place navigation test compared with the rats in model group (P>0.05). There were no significant difference in the total distance in last three days and times of crossing the platform among the six groups(2) The result of expression of Ache in cortexThere were no significant difference in expression of Ache in cortex among the six groups (P>0.05)(3) The expression of Bax in the hippocampus and cortexCompared with sham operation group, Bax level in hippocampus and cortex of the brain in model group was significantly increased (P<0.01). Compared with modle group, Bax expressions in hippocampus and cortex in donepezil treated group and various dose groups of combination of β-asarone and eugenol were significantly decreased (P<0.01)(4) The expression of Smad2in the hippocampus and cortexCompared with sham operation group, Smad2level in hippocampus and cortex of the brain in model group was significantly decreased (P<0.01). Compared with modle group, Smad2expressions in hippocampus in donepezil treated group and various dose groups of combination of β-asarone and eugenol were significantly increased (P<0.01), the expression in cortex in high dose group was significantly increased (P<0.01)(5) Cell apoptosis measured by TunelCompared with sham operation group, the numbers of apoptotic cells in hippocampus and cortex of the brain were significantly increased in model group (P<0.01). Compared with modle group, the numbers of apoptotic cells in hippocampus and cortex were significantly decreased in donepezil treated group and various dose groups of combination of β-asarone and eugenol (P<0.01, P<0.05). Conclusion(1) Learning memory dysfunction was caused by injection Ibotenic into the bilateral NBM of rats. Bax level was increased while Smad2level was decreased in hippocampus and cortex of the brain.(2) High dose of the combinations of β-asarone and eugenol in Acorus Tatarinowii may improve Learning-Memory Ability in Dementia Model Rats. While the low dose and middle dose has no such effect. The results suggest that the effect of combination of β-asarone and eugenol on nervous system may be in dose dependent manner. (3) The mechanisms of combination of β-asarone and eugenol in Acorus Tatarinowii on rescuing the Learning and memory deficits may be by up-regulating Smad2expression and down-regulating Bax expression which result in decreasing cell apoptosis.