1. Academic Validation
  2. Artesunate alleviates intestinal ischemia/reperfusion induced acute lung injury via up-regulating AKT and HO-1 signal pathway in mice

Artesunate alleviates intestinal ischemia/reperfusion induced acute lung injury via up-regulating AKT and HO-1 signal pathway in mice

  • Int Immunopharmacol. 2023 Jul 11;122:110571. doi: 10.1016/j.intimp.2023.110571.
Tuo Ji 1 Meng Chen 2 Yinyin Liu 3 Haixing Jiang 4 Na Li 5 Xianghu He 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, 169 East Lake Road, Wuhan, Hubei 430071, China; Department of Anesthesiology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China. Electronic address: jiituo@foxmail.com.
  • 2 Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, 745 Wuluo Road, Wuhan, Hubei 430070, China. Electronic address: chenm1106@163.com.
  • 3 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, 169 East Lake Road, Wuhan, Hubei 430071, China. Electronic address: yinyinliu@whu.edu.cn.
  • 4 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, 169 East Lake Road, Wuhan, Hubei 430071, China. Electronic address: 283984116@qq.com.
  • 5 Department of Anesthesiology, Maternal and Child Health Hospital of Hubei Province, 745 Wuluo Road, Wuhan, Hubei 430070, China. Electronic address: lina@hbfy.com.
  • 6 Department of Anesthesiology, Zhongnan Hospital of Wuhan University, 169 East Lake Road, Wuhan, Hubei 430071, China. Electronic address: hexh1220@aliyun.com.
Abstract

Acute Lung injury (ALI) is a common complication following intestinal ischemia/reperfusion (II/R) injury that can lead to acute respiratory distress syndrome (ARDS) a fatal illness for there is no specific therapy. The semisynthetic artemisinin Artesunate (Art) extracted from Artemisia annua has been found lots of pharmaceutical effects such as anti-malaria, anti-inflammatory, and anti-apoptosis. This study aimed to investigate the effect of Artesunate on intestinal ischemia/reperfusion and the mechanism of how Artesunate works in mice. To establish the II/R model, the C57BL/c mice were subjected to occlude superior mesenteric artery (SMA) for 45 min and 120 min reperfusion, and the lung tissue was collected for examination. Severe lung injury occurred during the II/R, meanwhile Art pretreatment decreased the lung injury score, wet/dry ratio, the level of MDA, MPO, IL-1β, TNFα, CXCL1, MCP-1, the TUNEL-positive cells, Bax and Cleaved-Caspase3 protein expression obviously, and increased the activity of SOD and the expression of Bcl-2. In addition, the protein of P-AKT and HO-1 were upregulated during the Art pretreatment. Then the Akt Inhibitor Triciribin and HO-1 inhibitor Tin-protoporphyrin IX were administered which reversed the protein expression of Apoptosis, Akt and HO-1. Our study suggests that Art mitigated the II/R induced acute lung injury by targeting the oxidative stress, inflammatory response and Apoptosis which is associated with the activating of Akt and HO-1, providing novel insights into the therapeutic candidate for the treatment of II/R induced acute lung injury.

Keywords

AKT; Apoptosis; Artesunate; HO-1; II/R - ALI.

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