α-Cyperone Attenuates H2O2-Induced Oxidative Stress and Apoptosis in SH-SY5Y Cells via Activation of Nrf2
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α-cyperone, extracted from Cyperus rotundus, has been reported to inhibit microglia-mediated neuroinflammation. Oxidative stress and apoptosis play crucial roles in the course of Parkinson's disease (PD). PD is a common neurodegenerative disease characterized by selective death of dopaminergic neurons. This study was designed to investigate the neuroprotective effects of α-cyperone against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in dopaminergic neuronal SH-SY5Y cells. Neurotoxicity was assessed by MTT assay and measurement of lactic dehydrogenase (LDH) release. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. The apoptosis of SH-SY5Y cells was evaluated by annexin-V-FITC staining. The translocation of NF-E2-related factor 2 (Nrf2) was determined by western blot and immunofluorescence staining. Western blot analysis was conducted to determine the expression level of cleaved-caspase-3, the pro-apoptotic factor Bax, and the anti-apoptotic factor, Bcl-2. The results showed that α-cyperone substantially decreased H2O2-induced death, release of LDH, and production of ROS in SH-SY5Y cells. In addition, we found that α-cyperone attenuated H2O2-induced cellular apoptosis. Moreover, α-cyperone remarkably reduced the expression of cleaved-caspase-3 and Bax, and upregulated Bcl-2. Furthermore, α-cyperone enhanced the nuclear translocation of Nrf2. Pretreatment with brusatol (BT, an Nrf2 inhibitor) attenuated α-cyperone-mediated suppression of ROS, cleaved-caspase-3, and Bax, as well as α-cyperone-induced Bcl-2 upregulation in H2O2-treated SH-SY5Y cells. α-cyperone neuroprotection required Nrf2 activation. In conclusion, α-cyperone attenuated H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells via the activation of Nrf2, suggesting the potential of this compound in the prevention and treatment of PD.
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The human neuroblastoma SH-SY5Y is among the most used cell lines, a subclone of the parental neuronal line SK-N-SH, which originated in 1970 from a biopsy metastatic tumor.
“The human neuroblastoma SH-SY5Y is among the most used cell lines [131,136,137,138,139,140,141,142], a subclone of a parental neuronal line SK-N-SH, which originated in 1970 from a biopsy metastatic tumor.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [131]
In vitro models with neurons isolated from the CNS and/or immortalized cell lines demonstrated that H2O2 causes cell death through apoptosis.
“Various in vitro models carried out with neurons isolated from the CNS and/or with immortalized cell lines, demonstrated that H2O2 causes cell death through apoptosis [118,131,132,133,134,135].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [131]
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- Authors
- Huang, B., Liu, J., Fu, S., Zhang, Y., Li, Y., He, D., Ran, X., Yan, X., Du, J., Meng, T., Gao, X., & Liu, D.
- Affiliations
- Jilin University (CN)
- Corresponding author
- Liu, Dianfeng
- ORCID
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2020-04-08
- Volume
- 11
- Pages
- 281-281
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC7156596
- OpenAlex
- W3016046180
- Cited by
- 62
- References
- 52
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 7 · 2023: 9 · 2022: 9 · 2021: 12 · 2020: 2
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31772547, 31672509)
- Jilin Scientific and Technological Development Program (20170623083-04TC, 20170623029 TC, 31672509)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- α-cyperone, Cyperus rotundus, Nrf2, oxidative stress, apoptosis, Parkinson's disease, dopaminergic neurons, SH-SY5Y cells, hydrogen peroxide, reactive oxygen species, caspase-3, Bax, Bcl-2, brusatol, neuroprotection
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