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Astrocytic Nrf2 Mediates the Neuroprotective and Anti-Inflammatory Effects of Nootkatone in an MPTP-Induced Parkinson’s Disease Mouse Model
- Title
- Astrocytic Nrf2 Mediates the Neuroprotective and Anti-Inflammatory Effects of Nootkatone in an MPTP-Induced Parkinson’s Disease Mouse Model
- Authors
- Park; Jung-Eun; Leem; Yea-Hyun; Jin-Sun; Kim; Seong-Eun; Hee-Sun
- Ewha Authors
- 김희선; 김성은; 박진선; 임예현
- SCOPUS Author ID
- 김희선; 김성은; 박진선; 임예현
- Issue Date
- 2023
- Journal Title
- Antioxidants
- ISSN
- 2076-3921
- Citation
- Antioxidants vol. 12, no. 11
- Keywords
- anti-inflammation; astrocyte; neuroprotection; nootkatone; Nrf2; Parkinson’s disease
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- This study aims to investigate the neuroprotective effects of nootkatone (NKT), a sesquiterpenoid compound isolated from grapefruit, in an MPTP-induced Parkinson’s disease (PD) mouse model. NKT restored MPTP-induced motor impairment and dopaminergic neuronal loss and increased the expression of neurotrophic factors like BDNF, GDNF, and PGC-1α. In addition, NKT inhibited microglial and astrocyte activation and the expression of pro-inflammatory markers like iNOS, TNF-α, and IL-1β and oxidative stress markers like 4-HNE and 8-OHdG. NKT increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)-driven antioxidant enzymes like HO-1 and NQO-1 in astrocytes, but not in neurons or microglia in MPTP-treated mice. To investigate whether Nrf2 mediates the anti-inflammatory, antioxidant, or neuroprotective effects of NKT, mice were pretreated with Nrf2-specific inhibitor brusatol (BT) prior to NKT treatment. BT attenuated the NKT-mediated inhibition of 4-HNE and 8-OHdG and the number of Nrf2+/HO-1+/NQO1+ cells co-localized with GFAP+ astrocytes in the substantia nigra of MPTP-treated mice. In addition, BT reversed the effects of NKT on dopaminergic neuronal cell death, neurotrophic factors, and pro-/anti-inflammatory cytokines in MPTP-treated mice. Collectively, these data suggest that astrocytic Nrf2 and its downstream antioxidant molecules play pivotal roles in mediating the neuroprotective and anti-inflammatory effects of NKT in an MPTP-induced PD mouse model. © 2023 by the authors.
- DOI
- 10.3390/antiox12111999
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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antioxidants-12-01999.pdf(5.18 MB)
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