Amygdalin alleviates LPS-induced acute lung injury in mice by targeting CD5L/iNOS pathway

Abstract

Amygdalins (AMY) from bitter almonds are distinguished by their anti-inflammatory, antibacterial and antioxidant properties, but their role in the treatment of acute lung injury (ALI) and their mechanisms need to be clarified. We sought to investigate whether AMY provides protection against lipopolysaccharide (LPS)-induced ALI in mice and explore the mechanisms of its protection. Results showed that AMY effectively alleviated LPS-induced ALI in a dose-dependent manner by reducing in vivo lung wet/dry ratio, lung/body weight ratio, and myeloperoxidase (MPO). In addition, AMY can significantly reduce lung histopathological injury, decreased bronchoalveolar lavage fluid (BALF) lymphocyte, neutrophil, and monocyte numbers, and decreased the secretion of inflammatory cytokines IL-6, IL-1β, and TNF-α. Through transcriptome sequencing, AMY was found to effectively reduce the mRNA level of CD5L in mice. In AAV-CD5L transfected mice, CD5L overexpression was found to block the protective effect of AMY in LPS-induced ALI mice. It was revealed that AMY inhibited NF-κB entry into the nucleus to reduce iNOS by targeting CD5L. Taken together, AMY can effectively reduce lung inflammation and alleviate ALI, and is a potential novel protective agent against LPS-induced ALI.