Cardamonin protects septic mice from acute lung injury by preventing endothelial barrier dysfunction.
Cardamonin, a flavone compound isolated from Alpinia katsumadai Heyata seeds, has been reported to possess anti-inflammatory and anticoagulative activities, and it might be beneficial for management of sepsis. This study was conducted to examine the protective effects of cardamonin on experimental sepsis and resultant acute lung injury (ALI). Cardamonin (30 and 100 mg/kg) significantly elevated the survival rate of septic mice, alleviated ALI and lung microvascular leak, and lowered the serum levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6. In vitro, it (25 and 50 µM) concentration dependently inhibited endothelium permeability and downregulated phosphorylation of P38 in rat lung microvascular endothelial cells induced by lipopolysaccharide (LPS). P38 inhibitor inhibited the endothelium permeability. In RAW 264.7 macrophage cells, cardamonin also showed selective inhibition of P38 phosphorylation induced by LPS. These results indicate that cardamonin can protect septic mice from ALI by preventing endothelium barrier dysfunction via selectively inhibiting P38 activation.
State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Zhifeng
Z
Wei
Jian
J
Yang
Yu-Feng
YF
Xia
Wen-Zhe
WZ
Huang
Zheng-Tao
ZT
Wang
Yue
Y
Dai
D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D002478:Cells, Cultured; D047188:Chalcones / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D010539:Permeability / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047188:Chalcones; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C436747:cardamonin