title: Effect and mechanism of fuzhisan and donepezil on the sirtuin 1 pathway and amyloid precursor protein metabolism in PC12 cells.
abstract: The present study aimed to determine the effect and mechanism of fuzhisan (FZS) and donepezil on the SIRT1 signaling pathway and the metabolism of the amyloid precursor protein (APP) in PC12 cells. An experimental cell model of PC12 cells with Aβ25‑35‑induced neurotoxicity was established and cell proliferation was determined by the MTT assay following treatment with donepezil and FZS. In addition, cell apoptosis was determined using DAPI staining and light microscopy. Furthermore, western blot analysis and ELISA were utilized to evaluate the expression levels of associated APP, Aβ40, Aβ42, sAPPα, sAPPβ, ADAM10, sirtuin 1 (SIRT1) and forkhead box O (FoxO) protein. The results indicated that the cell model was successfully established and FZS protected the PC12 cells from the neurotoxic effects of Aβ25‑35, in a similar effect to donepezil, in a dose‑dependent manner. The expression of APP remained at the same level during the experimental period. The levels of Aβ40, Aβ42 and sAPPβ were downregulated, where as sAPPα, ADAM10, SIRT1 and FoxO expression levels were upregulated. In conclusion, FZS treatment attenuated the Aβ25‑35‑induced neurotoxicity in vitro. The neuroprotective mechanism of FZS was determined, including the induction of ADAM10 and SIRT1‑FoxO pathway, which participated in the process of neuroprotection. The present study identified the neuroprotective function of FZS, which may protect against Aβ‑induced toxicity. Therefore, FZS may be used clinically as a beneficial therapeutic drug for the development or progression of Alzheimer's disease.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Sun
authors.affiliation: Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Sun
mesh_terms: D000072197:ADAM10 Protein / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D000077265:Donepezil; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007189:Indans / Q000494:pharmacology*; D016716:PC12 Cells; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000032:analysis / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D051858:Forkhead Transcription Factors; D007189:Indans; D010880:Piperidines; C543479:fuzhisan; D000077265:Donepezil; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; D056564:Sirtuin 1