Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in Mice.

Andrographolide sulfonate (Andro-S), a sulfonation derivative of andrographolide, is known to be effective in treating inflammation-related diseases, while the underlying mechanisms and global protein alterations in response to Andro-S remain unknown. This study aimed to investigate the pharmacological effects and potential targets of Andro-S in a murine model of acute lung injury (ALI). ALI was induced by aerosolized lipopolysaccharide (LPS) exposure before treatment with Andro-S. Inflammatory state of each treatment group was determined by histological analysis and quantification of inflammatory markers. Differentially expressed proteins in lung tissues were identified by an iTRAQ-based quantitative proteomic approach and further confirmed by immunohistochemistry analysis. Administration of Andro-S alleviated LPS-induced histological changes in the lung and reduced the expression of inflammatory markers in serum, bronchoalveolar fluid and lung tissues. Proteomic analysis identified 31 differentially expressed proteins from a total of 2,234 quantified proteins in the lung. According to bioinformatics analysis, neutrophil elastase (ELANE), cathepsin G (CTSG) and myeloperoxidase (MPO), three neutrophil-derived proteases related to immune system process and defense responses to fungi were chosen as potential targets of Andro-S. Further immunohistochemistry analysis confirmed the inhibitory effects of Andro-S on LPS-induced ELANE, CTSG and MPO up-regulation. These results indicate that Andro-S suppressed the severity of LPS-induced ALI, possibly by attenuating the expression of and neutrophil-derived proteases.