Attenuation of acute lung injury in mice by oxymatrine is associated with inhibition of phosphorylated p38 mitogen-activated protein kinase.
Oxymatrine is one of the alkaloids extracted from Chinese herb Sophora japonica (Sophora flavescens Ait.) with activities of anti-inflammation, inhibiting immune reaction, antivirus, protecting hepatocytes and antihepatic fibrosis. However, the effect of oxymatrine on acute lung injury (ALI) has not been known yet. In this study, the effect of oxymatrine on ALI was investigated using an oleic acid-induced ALI mouse model. Morphological findings showed that the oleic acid group demonstrated a marked lung injury represented by prominent atelectasis, intraalveolar and interstitial patchy hemorrhage, edema, thickened alveolar septum, formation of hyaline membranes and the existence of inflammatory cells in alveolar spaces. While in the oxymatrine/dexamethasone group, these changes were less severe and in the vicinity of the control group. Furthermore, pretreatment with oxymatrine significantly alleviated oleic acid-induced lung injury accompanied by reduction of lung index and wet-to-dry weight ratio, decreases in serum TNF-alpha level and inhibition of phosphorylated p38 MAPK. These findings suggest that oxymatrine has a beneficial effect on acute lung injury induced by oleic acid in mice and may inhibit the production of proinflammatory cytokine, TNF-alpha, by means of the inhibition of p38 MAPK.
Xu
G L
GL
Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, Nanjing 210097, China.
Yao
L
L
Rao
S Y
SY
Gong
Z N
ZN
Zhang
S Q
SQ
Yu
S Q
SQ
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004336:Drug Antagonism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008168:Lung / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008855:Microscopy, Electron, Scanning; D019301:Oleic Acid / Q000008:administration & dosage / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011807:Quinolizines; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D029909:Sophora / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism*; D000093842:Matrines
D000470:Alkaloids; D003907:Dexamethasone; D019301:Oleic Acid; D011807:Quinolizines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C037573:oxymatrine; D000093842:Matrines