Neuroprotective effect and the mechanism of Shenzao jiannao oral liquid on Alzheimer ’s disease model mice / 中国药房

ABSTRACT

OBJECTIVE To study the neuroprotective effects of Shenzao jianna o oral liquid （SZJN）on Alzheimer ’s disease （AD）model mice and its mechanism. METHODS The mice were randomly divided into sham operation group ，model group ， Donepezil hydrochloride tablet group （0.65 mg/kg），SZJN low-dose ，medium-dose and high-dose groups （0.3，1.5 and 7.5 g/kg， calculated by crude drug quantity ），with 12 mice in each group ，half male and half female. Each group was given relevant medicine（intragastric administration of water at constant volume in sham operation group and model group ），twice a day ，for consecutive 28 d. On the 15th day of administration ，intracerebroventricular injection of β-amyloid 1-42（Aβ1-42）combined with intraperitoneal injection of scopolamine hydrobromide were used to induce AD model. Morris water maze was used to detect the learning and memory ability of mice. HE staining and Nissl staining were used to evaluate the pathological changes of brain tissue in mice. The levels of MDA and SOD in brain tissue of mice were detected. The phosphorylation level of cyclic adenosine monophosphate response element binding protein （CREB） and expression of brain-derived neurotrophic factor （BDNF） in hippocampal tissues were detected by Western blot. RESULTS Compared with sham operation group ，the escape latency of the model group was significantly prolonged ，and the number of crossing the platform and the percentage of residence time in the target quadrant were significantly reduced （P＜0.01）. The level of SOD in brain tissue ，the phosphorylation level of CREB and the expression level of BDNF in hippocampus decreased significantly （P＜0.01），while the level of MDA increased significantly （P＜ 0.01）. In hippocampal CA 1 area and cortical tissue ，nerve cells showed significantly decreased number ，the disordered arrangement and large gap ；the shape of nucleus was irregular and deeply stained ，and Nissl body was blurred ，loosely arranged and the number decreased. Compared with model group ，the escape latency of mice in each dose group of SZJN was significantly shortened ，and the times of crossing the platform and the percentage of residence time in the target quadrant were significantly jing- increased（P＜0.01）. Above indexes of brain tissue in mice were reversed sig nificantly in SZJN high-dose group （P＜0.01），and pathological damage of brain tiss ue was improved. CONCLUSIONS SZJN can significantly improve the learning and memory ability of AD model mice ，and alleviate the pathological injury and oxidative stress of brain tissue ，which may be related to the activation of CREB/BDNF signaling pathway.