1. Academic Validation
  2. Curdione ameliorates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil extracellular trap formation

Curdione ameliorates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil extracellular trap formation

  • Int Immunopharmacol. 2023 May:118:110082. doi: 10.1016/j.intimp.2023.110082.
Kai Yang 1 Bin Wu 2 Wu Wei 3 Cuiyu Li 3 Lu Li 4 Zhukai Cong 5 Qian Xiang 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No.725, South Wanping Road, Xuhui District, Shanghai 200032, China.
  • 2 Department of Anesthesiology, Peking University Third Hospital, No. 49, North Garden Street, Haidian District, Beijing 100191, China.
  • 3 Department of Anesthesiology, the Eighth Medical Center, Chinese PLA (People's Liberation Army) General Hospital, No. A17, Heishanhu Road, Haidian District, Beijing 100091, China.
  • 4 Department of Infectious Diseases, Peking University Third Hospital, No. 49, North Garden Street, Haidian District, Beijing 100191, China.
  • 5 Department of Anesthesiology, Peking University Third Hospital, No. 49, North Garden Street, Haidian District, Beijing 100191, China. Electronic address: bycongzhukai@bjmu.edu.cn.
  • 6 Department of Anesthesiology, Peking University Third Hospital, No. 49, North Garden Street, Haidian District, Beijing 100191, China. Electronic address: xq17338136297@163.com.
Abstract

Sepsis-associated acute lung injury remains to be a major cause of morbidity and mortality worldwide, and there is a lack of effective therapeutic drugs. Curdione, an activeingredient of Curcuma zedoary, a traditional Chinese medicine (TCM), possesses a variety of pharmacological actions, such as anti-inflammatory, antioxidant and inhibition of platelet aggregation. However, whether curdione protects against sepsis-induced lung injury is still undetermined. In this study, we investigated the effects of curdione on sepsis-induced lung injury. Cecal ligation and puncture (CLP) surgery was performed in mice to establish a model of sepsis. Twenty-four hours after CLP, bronchoalveolar lavage fluid (BALF) and lung tissue samples were harvested for investigation. The protective effects of curdione on acute lung injury and potential mechanisms were explored by detecting pathological sections, exudative proteins, oxidative responses, inflammatory factors, platelet activation, neutrophil infiltration, and neutrophil extracellular trap (NET) formation in the lung and were further verified in vitro. We showed that treatment with curdione clearly relieved histopathological changes, reduced inflammatory cytokine elevation and total protein concentrations in BALF, and decreased oxidative stress responses in lung tissues. In addition, curdione inhibited platelet activation, further blocking the interaction between platelets and neutrophils. Finally, neutrophil infiltration and NET formation was also reduced in mice treated with curdione. In conclusion, curdione alleviates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil recruitment, infiltration, and NET formation as well as its anti-inflammatory and antioxidant properties. Curdione has great therapeutic potential in sepsis.

Keywords

Curdione; Lung injury; Neutrophil extracellular trap; Platelet; Sepsis.

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