Artesunate Protects LPS-Induced Acute Lung Injury by Inhibiting TLR4 Expression and Inducing Nrf2 Activation.
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.
Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Deli
D
Zhao
Department of CT, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Jinling
J
Zhang
Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Guangquan
G
Xu
Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. wangqiushi12@sina.com.
Qiushi
Q
Wang
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D000077332:Artesunate; D008070:Lipopolysaccharides; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000187:drug effects* / Q000378:metabolism; D020011:Protective Agents; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D037621:Artemisinins; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D020011:Protective Agents; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077332:Artesunate
HO-1; LPS; Nrf2; artesunate; lung injury