Scutellarin protects against lipopolysaccharide-induced acute lung injury via inhibition of NF-kappaB activation in mice.
This paper investigates the effect of natural scutellarin on acute lung injury (ALI) induced by Escherichia coli endotoxin lipopolysaccharide (LPS) in mice and its mechanism of action. Mouse ALI was induced by the injection of LPS (15 mg/kg) via the tail vein, and mice were intraperitoneally injected with 50 and 25 mg/kg of scutellarin before the LPS injection. The lung index, serum NO2(-)/NO3(-), and tumor necrosis factor-alpha (TNF-alpha) levels were determined using kits. The lung lesions were examined by light microscope. The mRNA levels of TNF-alpha, inducible nitric oxide synthase (iNOS), and FasL in pulmonary tissues were detected by RT-PCR. c-Fos, c-Jun, IkappaB, and iNOS proteins were detected by the western blotting method. Pretreatment with 25 and 50 mg/kg of scutellarin significantly reduced lung injury induced by LPS, which expressed in the decrease in lung morphological lesions, serum NO2(-)/NO3(-), TNF-alpha levels, lactate dehydrogenase release, and total protein in the lavage fluid of bronchoalveolar of the lung. The mRNA level of TNF-alpha, iNOS, the protein content of c-Fos, iNOS, and the activation of NF-kappaB in pulmonary tissues were all inhibited, while the lung glutathione level increased. In conclusion, scutellarin has protective action against LPS-induced lung damage in mice, and its underlying mechanism might be the inhibition of IkappaB alpha degradation and the expression of TNF-alpha mRNA.
Tan
Zheng-Huai
ZH
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Yu
Ling-Hong
LH
Wei
Huai-Ling
HL
Liu
Geng-Tao
GT
D000199:Actins / Q000097:blood / Q000378:metabolism; D055371:Acute Lung Injury / Q000139:chemically induced*; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry; D016762:Genes, fos / Q000187:drug effects; D005965:Glucuronates / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000097:blood / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*
D000199:Actins; D004731:Endotoxins; D005965:Glucuronates; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C484876:scutellarin; D047310:Apigenin; D052247:Nitric Oxide Synthase Type II