@article{APS10350,
author = {Shao-peng Lin and Jue-xian Wei and Jia-song Hu and Jing-yi Bu and Li-dong Zhu and Qi Li and Hao-jun Liao and Pei-yi Lin and Shan Ye and Sheng-qiang Chen and Xiao-hui Chen},
title = {Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in microglia},
journal = {Acta Pharmacologica Sinica},
volume = {42},
number = {7},
year = {2021},
keywords = {},
abstract = {Sepsis is life-threatening organ dysfunction due to dysregulated systemic inflammatory and immune response to infection, often leading to cognitive impairments. Growing evidence shows that artemisinin, an antimalarial drug, possesses potent anti- inflammatory and immunoregulatory activities. In this study we investigated whether artemisinin exerted protective effect against neurocognitive deficits associated with sepsis and explored the underlying mechanisms. Mice were injected with LPS (750 μg · kg−1 · d−1, ip, for 7 days) to establish an animal model of sepsis. Artemisinin (30 mg · kg−1 · d−1, ip) was administered starting 4 days prior LPS injection and lasting to the end of LPS injection. We showed that artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests, attenuated neuronal damage and microglial activation in the hippocampus. In BV2 microglial cells treated with LPS (100 ng/mL), pre-application of artemisinin (40 μΜ) significantly reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-6) and suppressed microglial migration. Furthermore, we revealed that artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway; knockdown of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin in BV2 microglial cells. In conclusion, atemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect is probably mediated by activation of the AMPKα1 signaling pathway in microglia.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10350}
}