Protostemonine effectively attenuates lipopolysaccharide-induced acute lung injury in mice

• Published in: Acta pharmacologica Sinica 2018-01, Vol.39 (1), p.85-96
• Main Authors: Wu, Ya-xian, He, Hui-qiong, Nie, Yun-juan, Ding, Yun-he, Sun, Lei, Qian, Feng
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - prevention & control; AKT protein; Alkaloids - administration & dosage; Alkaloids - therapeutic use; Animals; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cell activation; Chemical compounds; Edema; Immunology; Inflammation; Interleukin 6; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Internal Medicine; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lung - pathology; Lungs; Macrophage Activation; Macrophages; Macrophages - metabolism; MAP kinase; Medical Microbiology; Mice; Mice, Inbred C57BL; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Original; original-article; p38 Mitogen-Activated Protein Kinases - metabolism; Peroxidase - metabolism; Pharmacology/Toxicology; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Pulmonary Edema - prevention & control; RAW 264.7 Cells; Rodents; Traditional Chinese medicine; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vaccine
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2017.131

Protostemonine （PSN） is the main anti-inflammatory alkaloid extracted from the roots of Stemona sessilifolia （known as ＂Baibu＂ in traditional Chinese medicine）. Here, we reported the inhibitory effects of PSN on lipopolysaccharide （LPS）-induced macrophage activation in vitro and LPS-induced acute lung injury in mice. Macrophage cell line RAW264.7 cells and mouse bone marrow-derived macrophages （BMDMs） were treated with PSN （1, 3, 10, 30 and 100 pmol/L） for 0.5 h and then challenged with LPS （0.1 pg/mL） for 24 h. Pretreatment with PSN significantly inhibited LPS-induced phosphorylation of MAPKs and AKT, iNOS expression and NO production in the macrophages. C57BL/6 mice were intratracheally injected with LPS （5 mg/kg） to induce acute lung injury （ALl）. The mice were subsequently treated with PSN （10 mg/kg, ip） at 4 and 24 h after LPS challenge. PSN administration significantly attenuated LPS-induced inflammatory cell infiltration, reduced pro-inflammatory cytokine （TNF-α, IL-113 and IL-6） production and eliminated LPS-mediated lung edema. Furthermore, PSN administration significantly inhibited LPS-induced pulmonary MPO activity. Meanwhile, LPS-induced phosphorylation of p38 MAPK, iNOS expression and NO production in the lungs were also suppressed. The results demonstrate that PSN effectively attenuates LPS-induced inflammatory responses in vitro and in vivo; the beneficial effects are associated with the decreased phosphorylation of MAPK and AKT and the reduced expression of pro-inflammatory mediators, such as iNOS, NO and cytokines. These data suggest that PSN may be a potential therapeutic agent in the treatment of ALl.