[Effect of Active Ingredients of Qingxin Kaiqiao Recipe on Spatial Learning and Memory Capacities, and Expressions of Bax, Bcl-2, Caspase-3, and PAPP in Hippocampus of AD Model Rats].

Objective To observe the effects of active ingredients of Qingxin Kaiqiao Recipe (QKR) , such as saponins, volatile oils, effective compositions of polysaccharides, on expressions of Bcl-2 associated X protein (Bax) , B-cell lymphoma-2 (Bcl-2) , cysteinyl aspartate specific proteinase-3 (Caspase-3) , and β-amyloid precursor protein (pAPP) in hippocampus of Ap1_40-induced Alzheimer's disease (AD) model rats. Methods Totally 112 male Sprague-Dawley (SD) rats were randomly divided into 7 groups, i.e., the normal control group, the sham-operation group, the model group, the Aricept group, the saponin group, the volatile oil group, the polysaccharide group, 16 in each group. The AD rat model was established by injecting Aβ₁₋₄₀ from bilateral hippocampus. Equal volume of double distilled water was administered to rats by gastrogavage in the normal control group, the sham-operation group, the model group from the 2nd day after modeling, once per day for 2 successive weeks (at 10:00 am). Aricept (Donepezil Hydrochloride Tablet, 1. 67 mg/kg per day) , saponin (9 mL/kg per day) , benzene (3. 33 mL/kg per day) , and polysaccharides (8. 33 mL/kg per day) was administered to rats by gastro- gavage to the Aricept group, the saponin group, the volatile oil group, the polysaccharides group, re- spectively, once per day for 2 successive weeks (at 10:00 am). By the end of gastrogavage spatial learning and memory capacities were detected using Morris water maze (MWZ). Apoptosis in hippocam- pal CAI region was detected using TUNEL staining. Expressions of Bax, Bcl-2, Caspase-3, and PAPP were measured via Real-time fluorescent quantitative PCR, Western blot, and immunohistochemistry, respectively. Results There was no statistical difference in pre-modeling escape latency and times of crossing platforms among groups at the same time point (P >0. 05). Besides, escape latency was gradu- ally shortened as time went by. Compared with the model group, escape latency was shortened, and times of crossing platforms was significantly increased in the Aricept group and the saponin group (P < 0. 05, P <0. 01). Compared with the model group, the amount of apoptotic cells in hippocampal CA1 re- gion was obviously reduced (P <0. 05, P <0. 01) , expressions levels of Bax, Caspase-3, and pAPP were down-regulated, Bcl-2/Bax ratio was obviously elevated in the saponin group, the volatile oil group, the polysaccharide group (P <0. 05, P <0. 01). Conclusion Three active ingredients (spaonins, benzene, and polysaccharides) of QKR could improve spatial memory and learning capacities to different degrees, which might be possibly achieved by decreasing expressions of Bax, Caspase-3, PAPP in hippocampal CA1 region, elevating Bcl-2 expression, and inhibiting apoptosis in hippocampus.