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 pharmacologi...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.00939/full |
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| author | Fei Gao Xing Liu Ziying Shen Xiaohui Jia Han He Jing Gao Jianhong Wu Chunhong Jiang Hu Zhou Yiping Wang |
| author_facet | Fei Gao Xing Liu Ziying Shen Xiaohui Jia Han He Jing Gao Jianhong Wu Chunhong Jiang Hu Zhou Yiping Wang |
| author_sort | Fei Gao |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-04-13T02:09:07Z |
| publishDate | 2018-08-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-632b20a9055140e39e53b3d4c184579a2022-12-22T03:07:21ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-08-01910.3389/fphys.2018.00939346859Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in MiceFei Gao0Xing Liu1Ziying Shen2Xiaohui Jia3Han He4Jing Gao5Jianhong Wu6Chunhong Jiang7Hu Zhou8Yiping Wang9State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaDepartment of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaDepartment of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaDepartment of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaDepartment of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Innovative Natural Medicine and TCM Injections, Ganzhou, ChinaDepartment of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai, ChinaAndrographolide 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.https://www.frontiersin.org/article/10.3389/fphys.2018.00939/fullandrographolide sulfonateacute lung injuryiTRAQquantitative proteomicsimmunohistochemistry |
| spellingShingle | Fei Gao Xing Liu Ziying Shen Xiaohui Jia Han He Jing Gao Jianhong Wu Chunhong Jiang Hu Zhou Yiping Wang Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in Mice Frontiers in Physiology andrographolide sulfonate acute lung injury iTRAQ quantitative proteomics immunohistochemistry |
| title | Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in Mice |
| title_full | Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in Mice |
| title_fullStr | Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in Mice |
| title_full_unstemmed | Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in Mice |
| title_short | Andrographolide Sulfonate Attenuates Acute Lung Injury by Reducing Expression of Myeloperoxidase and Neutrophil-Derived Proteases in Mice |
| title_sort | andrographolide sulfonate attenuates acute lung injury by reducing expression of myeloperoxidase and neutrophil derived proteases in mice |
| topic | andrographolide sulfonate acute lung injury iTRAQ quantitative proteomics immunohistochemistry |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.00939/full |
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