Effects and Therapeutic Value of Ziziphi Spinosae Preparations and Haierfu on Alzheimer's Disease-Related Cerebral Secretase Activity

To investigate the effects of Ziziphi Spinosae preparations and traditional Chinese medicine Haierfu on β-amyloid cleaving enzyme activity in aluminum-induced Alzheimer's disease (AD) model mice, and their therapeutic effects. Sixty KM mice were randomly divided into four groups: normal group, model group, treatment group 1, and treatment group 2, with 15 mice in each group. During the modeling phase, the normal group received no treatment, while the model group and the two treatment groups were administered maltol and AlCl3 via intraperitoneal injection to establish the AD mouse model. After 30 days of injection modeling, treatment group 1 mice were administered 0.3 ml/mouse of diluted Ziziphi Spinosae preparation by gavage, and treatment group 2 mice were administered 0.3 ml/mouse of diluted Haierfu solution by gavage. The normal group and model group mice were administered an equal amount of distilled water by gavage, once daily for 5 consecutive weeks. Before exposure, after exposure, and after treatment, the learning and memory abilities of the mice were assessed using the Y-maze test. After the treatment, the brain tissues of the mice were taken and made into 10% brain homogenates to determine the activities of β-amyloid cleaving enzyme (BACE), α-secretase, γ-secretase, and acetylcholinesterase (AchE) in the brain. The results of the water maze test showed that the escape latency to reach the platform was significantly prolonged in the mice after modeling (P<0.01), and the time required for the mice to reach the platform was significantly shortened after treatment (P<0.01). The results of β-secretase activity in the brains of mice showed that the β-secretase activity of the two treatment groups was significantly lower than that of the model group mice. Sorted by normal group, model group, treatment group 1, and treatment group 2, the β-secretase activities were 9.54±1.31▲, 9.79±2.22▲, 6.92±2.97, 8.57±2.03 (u/L), respectively (F=2.902, P=0.051, compared with treatment group 1, ▲P<0.05). The α-secretase activities were 26.98±5.37▲▲, 25.97±3.52, 48.30±39.06▲▲, 24.10±2.80▲▲ (u/L), respectively (F=3.973, P=0.013, compared with treatment group 1, ▲▲P<0.01). The brain AchE activities were 0.08±0.02, 0.16±0.06▲▲, 0.15±0.07▲▲, 0.12±0.05▲ (u/mg.prot), respectively (F=6.833, P=0.001, compared with the normal group, ▲P<0.05, ▲▲P<0.01). Ziziphi Spinosae preparations and traditional Chinese medicine Haierfu can reduce β-amyloid cleaving enzyme activity in the brains of mice and improve cognitive dysfunction in AD mice.