title: Hepatoprotective effects of Sedum sarmentosum on D-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure.
abstract: The hepatoprotective effects of sarmentosin-containing extracts of Sedum sarmentosum (SS) in D-galactosamine (D-GalN) / lipopolysaccharide (LPS)-induced fulminant hepatic failure mouse model. Pretreatment with SS markedly protected mice from lethal liver injury, which has known to be associated with an abrupt elevation of serum tumor necrosis factor (TNF)-α level. Indeed, SS significantly blocked the elevation of TNF-α and alanine aminotransferase and aspartate aminotransferase as well. SS also remarkably reduced number of apoptotic hepatocytes and DNA fragmentation in the liver, which correlated with blockade of caspase-3 activation. In addition, SS suppressed the increased expression of toll-like receptor 4 (TLR4). The activation of c-Jun NH(2)-terminal kinase, extracellular signal-regulated kinase, and p38 induced by D-GalN/LPS was also significantly suppressed by SS treatment. Furthermore, SS significantly inhibited the activation of nuclear factor-κB. In RAW 264.7 cells stimulated with LPS, TNF-α release and TLR4 expression was suppressed by SS pretreatment, which was in line with in vivo results. These findings suggested that SS prevents D-GalN/LPS-induced fulminant hepatic failure, and this protection is likely associated with its anti-apoptotic activity and the down-regulation of mitogen activated protein kinase activity associated at least in part with suppressing the transcription of LPS receptors.
authors.affiliation: Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Lian
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wu
authors.forename: Xing Fu
authors.initials: XF
authors.lastname: Cai
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Nan
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D015536:Down-Regulation; D005688:Galactosamine; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D031963:Sedum / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D008070:Lipopolysaccharides; D009570:Nitriles; D010936:Plant Extracts; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C082842:sarmentosine; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D005947:Glucose