CZ2HF mitigates -amyloid 25-35 fragment-induced learning and memory impairment through inhibition of neuroinflammation and apoptosis in rats

Cu-zhi-2-hao-fang (CZ2HF), a traditional Chinese medicine, has been used clinically for the treatment of amnesia. However, whether CZ2HF is capable of alleviating learning and memory impairment in Alzheimer's disease (AD) remains to be elucidated. The present study was designed to explore the effect and mechanism of CZ2HF on -amyloid 25-35 (A(25-35))-induced impairment in the learning and memory of rats. Morris water maze test was used to determine spatial learning and memory ability in A(25-35)-induced AD rats and hippocampal neuronal damage and apoptosis were observed using hematoxylin and eosin staining, Nissl staining and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively. The levels of -amyloid 1-42 (A(1-42)), pro-inflammatory factors, such as cyclooxygenase-2 (COX-2), tumor necrosis factor- (TNF-) and interleukin-1 (IL-1) and apoptosis-associated genes including B cell leukemia/lymphoma 2 (Bcl-2), Bcl-2-associated X, apoptosis regulator (Bax), pro-caspase-3, inhibitor of B (IB-) degradation and phosphorylated-nuclear factor-B p65 (p-NF-B p65) activation were analyzed using western blotting. The findings of the present study revealed that CZ2HF treatment significantly attenuated A(25-35)-induced cognitive impairments in rats. Subsequently, CZ2HF treatment markedly inhibited neuronal damage and deletions. Furthermore, CZ2HF reduced TNF-, IL-1, COX-2 protein expression levels, Bax/Bcl-2 ratio, and reduced A(1-42) and active-caspase-3 levels. In addition, IB- degradation and p-NF-B p65 activation were reduced by CZ2HF. These findings suggested that CZ2HF treatment improved A(25-35)-induced learning and memory impairment and hippocampal neuronal injury, and its underlying mechanism may be due to the inhibition of neuroinflammation and neuronal apoptosis. CZ2HF may be a potential agent for the treatment of AD.