Fuzhisan, a chinese herbal medicine, suppresses beta-secretase gene transcription via upregulation of SIRT1 expression in N2a-APP695 cells.

The accumulation of β-amyloid (Aβ) peptide plaques is the major pathogenic event in Alzheimer's disease (AD). Because β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) cleaves APP at the first amino acid of the Aβ domain and is the rate-limiting enzyme for Aβ peptide generation, the level of this aspartic protease is a focus of AD research. Fuzhisan (FZS), a Chinese herbal complex prescription that has been used for the treatment of AD for over 20 years, is known to enhance metabolic activity and cognitive ability in aged rats and AD patients. To confirm whether FZS's therapeutic effect related to BACE1 pathway, we investigated the intracellular molecules expression change after FZS treatment in N2a-APP695 cell line. In this study, we demonstrated that BACE1 transcription and translation were reduced, and SIRT1 expression was elevated in the N2a-APP695 cells treated with FZS. The therapeutic efficacy of FZS in AD may be derived from the downregulation of BACE1 expression.