Tongluo Xingnao effervescent tablet reverses memory deficit and reduces plaque load in APPswe/PS1dE9 mice

Abstract

Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β (Aβ)-induced neurodegeneration is hypothesized to be the primary pathological mechanism of AD. Tongluo Xingnao effervescent tablets (TXET), based on the traditional Chinese formula Qionggui Tang, have been used to treat AD and other types of dementia in China for decades. In the present study, the effects of TXET on cognition deficit, amyloid-βproduction, amyloid precursor protein procession and β-secretase expression were investigated in the APPswe/PS1dE9 mouse model of AD. As expected, APPswe/PS1dE9 mice exhibited cognitive decline and higher levels of Aβ and plaques in the brain compared with normal mice; however, these changes were attenuated following TXET treatment. Levels of C-terminal fragment (CTF)-β protein were decreased following treatment with TXET; however, CTF-αlevels were unaffected. Furthermore, TXET treatment did not decreaseγ-secretase activity or levels of presenilin-1 (PS1), neprilysin or insulin-degrading enzyme. These results indicate that TXET may regulate Aβmetabolism by downregulating the expression of β-secretase. The results of the present study have laid the foundation for the development of a Chinese medicinal compound with a β-secretase inhibitor as the target for the treatment of AD.