The effects of Danggui-Shaoyao-San on neuronal degeneration and amyloidosis in mouse and its molecular mechanism for the treatment of Alzheimer’s disease
Cong Yang, Yousheng Mo, Huifang Chen, Yanhui Huang, Shaoling Li, Hong Wang, Shuiqing Huang, Xiang Chang, Qun Du, Qi Wang
Abstract
The abnormal deposition of the extracellular amyloid-β peptide is the typical pathological hallmark of Alzheimer’s disease. Strategies to reduce the amyloid-β deposition effectively alleviate the neuronal degeneration and cognitive deficits of Alzheimer’s disease. Danggui-Shaoyao-San has been considered a useful therapeutic agent known for the treatment of Alzheimer’s disease. However, the mechanism of Danggui-Shaoyao-San for the treatment of Alzheimer’s disease remains unclear. We investigated Danggui-Shaoyao-San’s effect on amyloidosis and neuronal degeneration in an APP/PS1 mouse model. We found Danggui-Shaoyao-San alleviated the cognitive deficits in APP/PS1 mice. Additionally, Danggui-Shaoyao-San ameliorated the neuronal degeneration in these mice. Danggui-Shaoyao-San reduced the amyloidosis and amyloid-β1-42 deposition in APP/PS1 mouse brain and down-regulated the receptor for advanced glycation end products, and up-regulated the level of low-density lipoprotein receptor-related protein-1. However, the protein expression of the β-amyloid precursor protein, β-Secretase and presenilin-1 (PS1) in the amyloid-β production pathway, and the expression of neprilysin and insulin-degrading enzyme in the amyloid-β degradation pathway were not altered. Our findings collectively suggest that Danggui-Shaoyao-San could ameliorate the amyloidosis and neuronal degeneration of Alzheimer’s disease, which may be associated with its up-regulation lipoprotein receptor-related protein-1 and down-regulation of the receptor for advanced glycation end products.