Astrocytic Nrf2 Mediates the Neuroprotective and Anti-Inflammatory Effects of Nootkatone in an MPTP-Induced Parkinson’s Disease Mouse Model
- 주제(키워드) anti-inflammation , astrocyte , neuroprotection , nootkatone , Nrf2 , Parkinson’s disease
- 등재 SCIE, SCOPUS
- OA유형 Gold Open Access; Green Open Access
- 발행기관 Multidisciplinary Digital Publishing Institute (MDPI)
- 발행년도 2023
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000213377
- 본문언어 영어
- Published As https://doi.org/10.3390/antiox12111999
- PubMed 38001852
초록/요약
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.
more