title: Oxymatrine attenuates bleomycin-induced pulmonary fibrosis in mice via             the inhibition of inducible nitric oxide synthase expression and the TGF-β/Smad             signaling pathway.
abstract: Oxymatrine (OM) is an alkaloid extracted from the Chinese herb Sophora flavescens             Ait. with a variety of pharmacological activities. The aim of this study was to             investigate the preventive effects of OM on bleomycin (BLM)-induced pulmonary             fibrosis (PF) and to further explore the underlying mechanisms. C57BL/6 mice were             randomly assigned to five groups: the saline sham group; the BLM group, in which             mice were endotracheally instilled with BLM (3.0 mg/kg); and the BLM plus OM groups,             in which OM was given to mice daily (10, 20 or 40 mg/kg) one day after BLM instillation             for 21 days. The bronchoalveolar lavage fluid (BALF) and lung tissues were collected             at 15 and 22 days post BLM administration, respectively. Lung tissues were stained             with hematoxylin and eosin (H&E) for histological evaluation. Levels of tumor             necrosis factor (TNF)-α, interleukin-6 (IL-6) and nitric oxide (NO) in mouse BALF             were measured, as well as myeloperoxidase (MPO) activity and malondialdehyde (MDA)             content in lung homogenates. The inducible nitric oxide synthase (iNOS) expression             in the lung tissues was determined by immunohistochemical staining, quantitative             real-time PCR and western blot analysis. Moreover, the expression of transforming             growth factor (TGF)-β1, Smad2, Smad3, p-Smad2 and p-Smad3 were also detected.             We found that OM improved BLM-induced lung pathological changes, inhibited MPO             activity and reduced MDA levels in a dose-dependent manner. OM also dose-dependently             inhibited the release of TNF-α and IL-6, and decreased the expression of iNOS             in lung tissues and thus prevented NO release in response to BLM challenge. In             addition, OM decreased the expression of TGF-β1, p-Smad2 and p-Smad3, which are             all important members of the TGF-β/Smad signaling pathway. Our study provides             evidence that OM significantly ameliorated BLM-induced PF in mice via the inhibition             of iNOS expression and the TGF-β/Smad pathway.
authors.affiliation: Institute of Respiratory Diseases, The First Affiliated Hospital                     of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Ma
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Li
mesh_terms: D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001761:Bleomycin / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011807:Quinolizines / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D029909:Sophora / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000903:Antibiotics, Antineoplastic; D000998:Antiviral Agents; D001761:Bleomycin; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase; D011807:Quinolizines; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C037573:oxymatrine; D000093842:Matrines