title: Bigelovii A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Blocking NF-κB and CCAAT/Enhancer-Binding Protein δ Pathways.
abstract: Optimal methods are applied to acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), but the mortality rate is still high. Accordingly, further studies dedicated to identify novel therapeutic approaches to ALI are urgently needed. Bigelovii A is a new natural product and may exhibit anti-inflammatory activity. Therefore, we sought to investigate its effect on lipopolysaccharide- (LPS-) induced ALI and the underlying mechanisms. We found that LPS-induced ALI was significantly alleviated by Bigelovii A treatment, characterized by reduction of proinflammatory mediator production, neutrophil infiltration, and lung permeability. Furthermore, Bigelovii A also downregulated LPS-stimulated inflammatory mediator expressions in vitro. Moreover, both NF-κB and CCAAT/enhancer-binding protein δ (C/EBPδ) activation were obviously attenuated by Bigelovii A treatment. Additionally, phosphorylation of both p38 MAPK and ERK1/2 (upstream signals of C/EBPδ activation) in response to LPS challenge was also inhibited by Bigelovii A. Therefore, Bigelovii A could attenuate LPS-induced inflammation by suppression of NF-κB, inflammatory mediators, and p38 MAPK/ERK1/2-C/EBPδ, inflammatory mediators signaling pathways, which provide a novel theoretical basis for the possible application of Bigelovii A in clinic.
authors.affiliation: Department of Pathogenic Biology and Immunology, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yan
authors.affiliation: Research Center for Natural Products Chemistry, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210004, China.
authors.forename: Fuqin
authors.initials: F
authors.lastname: Guan
authors.affiliation: Department of Bioengineering, Medical School of Southeast University, Nanjing 210009, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of the State Food and Drug Administration of China, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Intensive Care, Jintan Hospital, Jiangsu University, Changzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative & Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
authors.affiliation: Research Center for Natural Products Chemistry, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210004, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D015153:Blotting, Western; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; C575123:bigelovii A; D051743:CCAAT-Enhancer-Binding Protein-delta; D009195:Peroxidase