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Artesunate Protects LPS-Induced Acute Lung Injury by Inhibiting TLR4 Expression and Inducing Nrf2 Activation

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Abstract

Artesunate, a derivative of artemisinin, has been reported to have anti-inflammatory property. However, few studies showed the protective effects of artesunate on lung injury. In this study, we aimed to investigate the effects of artesunate on LPS-induced lung injury in mice. The mice were treated with artesunate 1 h before or after LPS treatment. The effects of artesunate on lung MPO activity and malondialdehyde (MDA) content were detected. The lung wet/dry radio and the numbers of inflammatory cells in BALF were also measured. ELISA was used to evaluate the levels of TNF-α, IL-1β, and IL-6 in BALF. Western blot analysis was adapted to detect TLR4 and Nrf2 signaling pathways. The results showed that artesunate protected against LPS-induced ALI by decreasing the numbers of inflammatory cells, lung edema, MPO activity, and MDA content. Furthermore, artesunate significantly inhibited the levels of TNF-α, IL-1β, and IL-6. Artesunate also inhibited LPS-induced IL-6 and IL-8 production in the A549 cells. In addition, artesunate dose-dependently suppressed LPS-induced TLR4 expression and NF-κB activation. The expression of Nrf2 and HO-1 were also up-regulated by artesunate. The data suggest that artesunate possesses anti-inflammatory and anti-oxidant properties against LPS-induced ALI via inhibiting TLR4 signaling pathway and activating Nrf2 signaling pathway.

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    Authors and Affiliations

    1. Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China

      Deli Zhao & Jinling Zhang

    2. Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China

      Guangquan Xu & Qiushi Wang

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    1. Deli Zhao
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    2. Jinling Zhang
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    3. Guangquan Xu
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    4. Qiushi Wang
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    Correspondence to Qiushi Wang.

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    Deli Zhao and Jinling Zhang contribute equally to this article.

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    Zhao, D., Zhang, J., Xu, G. et al. Artesunate Protects LPS-Induced Acute Lung Injury by Inhibiting TLR4 Expression and Inducing Nrf2 Activation. Inflammation 40, 798–805 (2017). https://doi.org/10.1007/s10753-017-0524-6

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