Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner
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
Affiliations
Chuan-Hsiu Liu
Graduate Institute of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Mei-Ying Chen
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Yueh-Hsiung Kuo
Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Jack Cheng
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Li-Zhong Chang
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Meng-Shiun Chang
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Tsai-Ni Chuang
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Wen-Tsong Hsieh
Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Yan-Ru Xiao
Department of Pharmacology, School of Medicine, China Medical University, Taichung 40402, Taiwan
Bor-Tsang Wu
Department of Senior Service Management, National Taichung University of Science and Technology, Taichung City 40343, Taiwan
Wei-Yong Lin
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Hsin-Ping Liu
Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
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.
