Effect and mechanism of fuzhisan and donepezil on the sirtuin 1 pathway and amyloid precursor protein metabolism in PC12 cells
Open accessAbstract
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.
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Fuzhisan inhibits Abeta25-35-induced neurotoxicity.
“Consequently, studies have shown that Fuzhisan inhibits Abeta25-35-induced neurotoxicity, with the induction of the ADAM10 and SIRT1-Fox0 pathway serving a potential role in neuroprotection, since PC12 cells treated with Fuzhisan demonstrated significantly elevated levels of ADAM10 [170].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [170]
PC12 cells treated with Fuzhisan demonstrated significantly elevated levels of ADAM10.
“Consequently, studies have shown that Fuzhisan inhibits Abeta25-35-induced neurotoxicity, with the induction of the ADAM10 and SIRT1-Fox0 pathway serving a potential role in neuroprotection, since PC12 cells treated with Fuzhisan demonstrated significantly elevated levels of ADAM10 [170].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [170]
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“Fuzhisan’s neuroprotective effects have been proposed to be associated with anti- Aβ accumulation and anti-apoptotic effects, as well as elevating acetylcholine levels and enhancing neurotropic effects [170].”
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- Authors
- GUO, P., WANG, D., WANG, X., FENG, H., TANG, Y., SUN, R., ZHENG, Y., DONG, L., ZHAO, J., ZHANG, X., WANG, S., & SUN, H.
- Affiliations
- Harbin Medical University (CN)
- Capital Medical University (CN)
- ORCID
- Venue
- Molecular Medicine Reports
- Publisher
- Spandidos Publications
- Published
- 2016-03-01
- Volume
- 13
- Issue
- 4
- Pages
- 3539-3546
- ISSN
- 1791-2997 (ISSN-L)
- 1791-3004
- OpenAlex
- W2290097945
- Cited by
- 30
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 8 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 3
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Medicine Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- donepezil, SIRT1, APP processing, ADAM10, FOXO, neuroprotection, Alzheimer's disease, PC12 cells, apoptosis, sAPPα, sAPPβ
- MeSH terms
- ADAM10 Protein, Donepezil, Animals, Drugs, Chinese Herbal, Enzyme-Linked Immunosorbent Assay, Indans, Piperidines, Blotting, Western, Signal Transduction, PC12 Cells, Rats, Forkhead Transcription Factors, Amyloid Precursor Protein Secretases, Sirtuin 1
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