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- Title
Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner.
- Authors
Liu, Chuan-Hsiu; Chen, Mei-Ying; Kuo, Yueh-Hsiung; Cheng, Jack; Chang, Li-Zhong; Chang, Meng-Shiun; Chuang, Tsai-Ni; Hsieh, Wen-Tsong; Xiao, Yan-Ru; Wu, Bor-Tsang; Lin, Wei-Yong; Liu, Hsin-Ping
- Abstract
Microglia are neuroglia in the brain with an innate immune function and participate in the progress of neurodegenerative diseases. Osthole (OST) is a coumarin derivative extracted from Cnidium monnieri and bears a microglia-antagonizing ability. However, the underlying mechanism of the antagonism is not clear. The lipopolysaccharides-induced microglial BV2 cell line and amyloid-overexpressing fruit fly were used as models to study OST treatment. We found that OST treatment is sufficient to evoke NRF2 cascade under an LPS-induced inflammatory environment, and silencing NRF2 is sufficient to abolish the process. Moreover, we found that OST is sufficient to antagonize microglial activation in both LPS-induced BV2 cells and Aβ-overexpressing fruit flies, and silencing NRF2 abolishes OST's antagonism. Furthermore, OST treatment rescued survival, climbing, and the learning ability of Aβ-overexpressing fruit flies and relieved oxidative stress. In conclusion, we proved that OST antagonizes microglial activation induced by either LPS or Aβ and that NRF2 is necessary for OST's antagonism.
- Subjects
MICROGLIA; FRUIT flies; NEUROGLIA; NUCLEAR factor E2 related factor; COUMARIN derivatives; LEARNING ability
- Publication
Molecules, 2023, Vol 28, Issue 2, p507
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules28020507