Andrographolide Protects against LPS-Induced Acute Lung Injury by Inactivation of NF-κB

• Published in: PloS one Vol. 8; no. 2; p. e56407
• Main Authors: Zhu, Tao, Wang, Dao-xin, Zhang, Wei, Liao, Xiu-qing, Guan, Xian, Bo, Hong, Sun, Jia-yang, Huang, Ni-wen, He, Jing, Zhang, Yun-kun, Tong, Jing, Li, Chang-yi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.02.2013; Public Library of Science (PLoS)
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - genetics; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Alveolar Epithelial Cells - pathology; Alveolar Epithelial Cells - ultrastructure; Alveoli; Andrographis; Animals; Binding sites; Biology; Bronchoalveolar Lavage Fluid; Cell adhesion & migration; Cell Count; Cell Survival - drug effects; Cell Survival - genetics; Cytokines - metabolism; Deactivation; Deoxyribonucleic acid; Diterpenes - pharmacology; Diterpenes - therapeutic use; DNA; DNA - metabolism; Down-Regulation - drug effects; Drug dosages; Edema; Epithelial cells; Gene expression; Gene Expression Regulation - drug effects; Herbal medicine; Hospitals; Hypoxia; In vitro methods and tests; In vivo methods and tests; Inactivation; Inflammation; Interleukin 6; Kinases; Laboratory animals; Leukocytes (neutrophilic); Lipopolysaccharides; Lungs; Macrophages; Male; Medicinal plants; Medicine; Mice; Mice, Inbred BALB C; NF-kappa B - metabolism; NF-κB protein; Pathogens; Peroxidase - metabolism; Phosphorylation; Pneumonia - complications; Pneumonia - drug therapy; Pneumonia - genetics; Pneumonia - pathology; Protective Agents - pharmacology; Protective Agents - therapeutic use; Protein Binding - drug effects; Protein Binding - genetics; Pulmonary Edema - complications; Pulmonary Edema - drug therapy; Pulmonary Edema - genetics; Pulmonary Edema - pathology; Respiratory distress syndrome; Rheumatoid arthritis; Rodents; Therapeutic applications; Traditional Chinese medicine; Transcription Factor RelA - metabolism; Tumor necrosis factor-α; Ultrastructure; Vascular cell adhesion molecule 1; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056407

Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.