The Effect Of Active Ingredient Combinat In Acorus Tatarinowii Schott On Learning-Memory Ability In SAMP8and Its Mechanism

ObjectivesTo observe the influence in compatibility of active ingredients β-asarone with eugenol (4:1) in Acorus Tatarinowii Schott on learning-memory ability in senescence accelerated mouse-Prone/8(SAMP8).MethodsThe6-month-old male SAMP8were randomly divided into5groups (12-13in each group):SAMP8model group, huperzine A group,β-asarone group, low and high-dose of active ingredients combination groups; In addition,13male SAMR1with the same age as the negative control. The drug was administered by gavage for2months, except of that the negative control group and model group were administered with same volume of distilled water. Spatial learning and memory were tested by Morris water maze tests. Concomitant apoptosis in the brain tissue was quantified by TUNEL assay. The expression of Aβ42and Bax were measured by immunohistochemistry; protein level of phospho-tau and Bcl-2were measured using western Blotting.Reasult(1) Morris water maze testCompared with SAMR1group, SAMP8model group showed prolonged swimming time and distance (P<0.01). Compared with SAMP8model group, the swimming time and distance in the low-dose groups of effective chemical combination were significantly decreased (P<0.01, P<005)(2) the incidence rate of neuronal apoptosis in the hippocampus and cortex Compared with the negative SAMR1, the incidence rate of neuronal apoptosis in the hippocampus CA1area and cortex of the brain was significantly increased in model group (P<0.01). Compared with the model group, the incidence rate of neuronal apoptosis in the hippocampus CAl area and cortex of Huperzine A group and ow-dose of active ingredients combination group were both significantly decreased (P<0.01)(3) the expression of Aβ42in the cotexComPared with the negative SAMR1, Aβ42level in the cortex of the brain was significantly increased in model group (P<0.01). Compared with the model group, the expression of Aβ42in the cortex of each other group did not show significant difference (P>0.05)(4) the expression of p-tau (thr231) in the hippocampusCompared with the model group, the p-tau(thr231) exPression in the negative group showed a decreasing trend, but did not show significant difference (P>0.05)(5) the expression of Bcl-2in the hippocampusCompared with the model group, the Bcl-2expression of the negative group、Huperzine treated group and the low-dose of active ingredients combination group showed a increasing trend, but did not show significant difference (P>0.05)(6) the expression of Bax in the hippocampus and cotexCompared with the negative SAMR1, Bax level in the hippocampus CAl area and cortex of the brain was significantly increased in model group (P<0.01) While the expressions of Bax in the hippocampus CAl area and cortex in huperzine A group and low-dose of active ingredients combination group were significantly decreased than that in model grouP (P<0.01). However, Bax exPression in high-dose of active ingredients group and β-asarone group showed a significant increase than that in low-dose of active ingredients group (P<0.01)Conclus ionThe SAMP8exhibited sptial learning and memory impirment in the Morris water maze tests, and high incidence rate of neuronal aPoPtosis in the hiPPocamPus CAl and cortex at8months of age. Low-dose of active ingredients combination in Acorus Tatarinowii Schott can effectively decrease neural cell aPoPtosis and Bax exPression, which may be a mechanism for its effect on imProving learning and memory ability in SAMP8.