Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner
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 <i>Cnidium monnieri</i> and bears a microglia-antagonizing ability. However, the underlying mechanism o...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/2/507 |
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| author | Chuan-Hsiu Liu Mei-Ying Chen Yueh-Hsiung Kuo Jack Cheng Li-Zhong Chang Meng-Shiun Chang Tsai-Ni Chuang Wen-Tsong Hsieh Yan-Ru Xiao Bor-Tsang Wu Wei-Yong Lin Hsin-Ping Liu |
| author_facet | Chuan-Hsiu Liu Mei-Ying Chen Yueh-Hsiung Kuo Jack Cheng Li-Zhong Chang Meng-Shiun Chang Tsai-Ni Chuang Wen-Tsong Hsieh Yan-Ru Xiao Bor-Tsang Wu Wei-Yong Lin Hsin-Ping Liu |
| author_sort | Chuan-Hsiu Liu |
| collection | DOAJ |
| description | 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 <i>Cnidium monnieri</i> 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. |
| first_indexed | 2024-03-09T11:37:29Z |
| format | Article |
| id | doaj.art-c39652f6e11045a0a538c16883faba61 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:37:29Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c39652f6e11045a0a538c16883faba612023-11-30T23:40:50ZengMDPI AGMolecules1420-30492023-01-0128250710.3390/molecules28020507Osthole Antagonizes Microglial Activation in an NRF2-Dependent MannerChuan-Hsiu Liu0Mei-Ying Chen1Yueh-Hsiung Kuo2Jack Cheng3Li-Zhong Chang4Meng-Shiun Chang5Tsai-Ni Chuang6Wen-Tsong Hsieh7Yan-Ru Xiao8Bor-Tsang Wu9Wei-Yong Lin10Hsin-Ping Liu11Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanDepartment of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanDepartment of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung 40402, TaiwanDepartment of Senior Service Management, National Taichung University of Science and Technology, Taichung City 40343, TaiwanGraduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanGraduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung 40402, TaiwanMicroglia 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 <i>Cnidium monnieri</i> 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.https://www.mdpi.com/1420-3049/28/2/507ostholeNRF2microglia |
| spellingShingle | Chuan-Hsiu Liu Mei-Ying Chen Yueh-Hsiung Kuo Jack Cheng Li-Zhong Chang Meng-Shiun Chang Tsai-Ni Chuang Wen-Tsong Hsieh Yan-Ru Xiao Bor-Tsang Wu Wei-Yong Lin Hsin-Ping Liu Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner Molecules osthole NRF2 microglia |
| title | Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner |
| title_full | Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner |
| title_fullStr | Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner |
| title_full_unstemmed | Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner |
| title_short | Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner |
| title_sort | osthole antagonizes microglial activation in an nrf2 dependent manner |
| topic | osthole NRF2 microglia |
| url | https://www.mdpi.com/1420-3049/28/2/507 |
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