Icaritin Improves Memory and Learning Ability by Decreasing BACE-1 Expression and the Bax/Bcl-2 Ratio in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice.

Icaritin (ICT) is the main component in the traditional Chinese herb Epimedium, and it has been shown to have anti-Alzheimer's disease (AD) effects, but its neuroprotective effects and the pharmacological mechanisms are unclear. In the present study, senescence-accelerated mouse prone 8 (SAMP8) mice were randomly divided into a model group and an ICT-treated group. Learning and memory abilities were detected by the Morris water maze assay, and the expression of amyloid beta protein (Aß) and ß-site APP cleavage enzyme 1 (BACE1) was determined by Western blotting and polymerase chain reaction (PCR). Histological changes in CA1 and CA3 were detected by hematoxylin-eosin staining (H&E staining), and the immunohistochemical analysis was used to detect the expression and localization of Bax and Bcl-2. The results showed that compared with the SAMP8 mice, the ICT-treated SAMP8 mice showed improvements in spatial learning and memory retention. In addition, the number of necrotic cells and the morphological changes in CA1 and CA3 areas were significantly alleviated in the group of ICT-treated SAMP8 mice, and the expression of BACE1, Aß 1-42 levels, and the Bax/Bcl-2 ratio in the hippocampus was obviously decreased in the ICT-treated group compared with the control group. The results demonstrated that ICT reduced BACE-1 levels, the contents of Aß 1-42, and the Bax/Bcl-2 ratio, suggesting that ICT might have potential therapeutic benefits by delaying or modifying the progression of AD.

Icariin improves cognitive deficits by reducing the deposition of ß-amyloid peptide and inhibition of neurons apoptosis in SAMP8 mice.

Effective therapeutic drugs for prevent or reverse the pathobiology of Alzheimer's disease (AD) have not been developed. Icariin (ICA), a prenylated flavonol glycoside derived from the traditional Chinese herb Epimedium sagittatum, exerts a variety of pharmacological activities and shows promise in the treatment and prevention of AD. This study investigated the neuroprotective effects of ICA in SAMP8 mice model of aspects of early AD and explored potential underlying mechanisms. Our results showed that intragastric administration of ICA could reverse the learning and memory impairment of SAMP8 mice in the Morris water maze. Western blot of hippocampal specimens revealed that ICA down-regulated the expression of BACE1 to reduce the expression of cytotoxic Aß1-42. Furthermore, ICA siginificantly increase the Bcl-2/Bax ratio by increasing the expression of anti-apoptotic protein Bcl-2, and decreasing the expression of pro-apoptotic protein Bax, and thus inhibit neurons apoptosis. These findings indicate that ICA could improve cognitive deficits by reducing the deposition of ß1-42 and inhibition of neurons apoptosis and provide further evidence for the clinical efficacy of ICA in the treatment of AD.