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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-12-20
pubmed:abstractText
The preventive effects of cepharanthine, a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata, on the lethality and cell death caused by endotoxin or tumor necrosis factor (TNF)-alpha-induced syndrome in septic shock were investigated. In these experiments, we estimated the survival of mice treated with a lethal dose of endotoxin (50 mg/kg, i.p.) or recombinant human (rh) TNF-alpha (10,000 units/mouse, i.v.) together with a sublethal dose (1 mg/kg, i.p.) of endotoxin. Cepharanthine clearly protected mice from endotoxin-induced and endotoxin/rhTNF-alpha-induced lethal shock. In in vitro experiments, cepharanthine (3 micro g/ml) definitely inhibited cell death in mouse L929 fibroblast cells incubated with rhTNF-alpha (100 units/ml) at 37 degrees C for 24 h. On the other hand, non-apoptotic programmed death of cells was observed by fluorescence microscopy in rhTNF-alpha (100 units/ml)-treated L929 cells. In the 3-(4,5-Dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay after 48-h drug exposure, the cell proliferation of L929 cells was significantly increased by the addition of cepharanthine (1 and 3 micro g/ml). It seems that the preventive effect of cepharanthine on rhTNF-alpha-induced cytotoxicity in fibroblast cells occurs through an increase of cell proliferation by the drug. In addition, cepharanthine suppressed nitric oxide (NO) production by endotoxin-stimulated Raw 264.7 mouse macrophage cells. These findings suggest that cepharanthine prevents lethality or cytotoxicity through suppression of endotoxin-induced NO in macrophages and that its effects are possibly mediated by the enhancement of the proliferation of fibroblast cells. Cepharanthine may therefore protect against some of the various disturbances caused by endotoxin through its ability to inhibit NO production in septic shock.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1567-5769
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Preventive effects of a biscoclaurine alkaloid, cepharanthine, on endotoxin or tumor necrosis factor-alpha-induced septic shock symptoms: involvement of from cell death in L929 cells and nitric oxide production in raw 264.7 cells.
pubmed:affiliation
Department of Environmental Health Science, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Sendai, Japan. shuhei@tohoku-pharm.ac.jp
pubmed:publicationType
Journal Article