title: Lobeline improves acute lung injury via nuclear factor-κB-signaling pathway and oxidative stress.
abstract: Acute lung injury (ALI) is a severe, life-threatening medical condition whose pathogenesis is linked to neutrophil infiltration of the lung. Activation and recruitment of neutrophils to the lung is mostly attributed to the production of chemokines NO, IL-6, for instance. This study aims to investigate lobeline ability in reducing NO production, and nitric oxide synthase (iNOs) expression. Lobeline was tested by inhibiting phosphorylation of mitogen-activated protein kinases (MAPKs), NF-κB and IκBα in LPS-stimulated RAW 264.7 cells. When RAW 264.7 macrophages were given lobeline with LPS, a significant concentration-dependent inhibition of NO production was detected. In vivo tests, mice were either treated with normal saline, 10mg/kg dexmethasone or 5, 10, 20mg/kg lobeline intraperitoneally, and after an hour, the administration of 5mg/kg of LPS was given intratracheally. External performance, cytokines, MAPK pathways and antioxidative enzymes (AOEs) were also carried out to evaluate the effects of these drugs. This is the first investigation in which lobeline was found to effectively inhibit acute lung edema, which may provide a potential target for treating ALI. Lobeline may utilize MAPKs pathways as well as AOEs activity to attenuate LPS-induced nonspecific pulmonary inflammation.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan.
authors.forename: Kun-Cheng
authors.initials: KC
authors.lastname: Li
authors.affiliation: Department of Nursing, Hungkuang University, Taichung 433, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Ho
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Cing-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Wen-Tsong
authors.initials: WT
authors.lastname: Hsieh
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan; Chinese Crude Drug Pharmacy, China Medical University Hospital, Taichung 404, Taiwan. Electronic address: yschang@mail.cmu.edu.tw.
authors.forename: Yuan-Shiun
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan. Electronic address: gjhuang@mail.cmu.edu.tw.
authors.forename: Guan-Jhong
authors.initials: GJ
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides; D008120:Lobeline / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D008120:Lobeline; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D020928:Mitogen-Activated Protein Kinases
keywords: ALI; AOEs; IκBα; Lobeline; MAPKs; NF-κB