title: Echinacea alkamides prevent lipopolysaccharide/D-galactosamine-induced acute hepatic injury through JNK pathway-mediated HO-1 expression.
abstract: This study aimed to shed light on the anti-inflammatory and hepatoprotective effect of the major alkamides dodeca-2E,4E,8Z,10Z(E)-tetraenoic acid isobutylamides (Alk-8/9), isolated from Echinacea purpurea roots, against acute fulminant hepatitis induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. The results show that Alk-8/9 dose-dependently induced heme oxygenase (HO)-1 protein expression in LPS-stimulated murine macrophages that was likely regulated by the JNK-mediated pathway through increasing SAPK/JNK phosphorylation, c-jun protein expression, and phosphorylation, and transcription factor AP-1 binding consensus DNA activity. The HO-1 inhibitor or CO scavenger significantly reversed the inhibitory effect of Alk-8/9 on TNF-α expression, whereas N-acetyl-L-cysteine was observed to reduce Alk-8/9-induced HO-1 expression in LPS-treated macrophages. Furthermore, Alk-8/9 markedly induced c-jun and HO-1 protein expression and suppressed serum aminotransferase activities, TNF-α expression, and hepatocyte damage in liver tissues of LPS/d-GalN-treated mice. This paper suggests a new application of Echinacea, a top-selling herbal supplement, as a hepatoprotective agent.
authors: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, Republic of China.
authors: Chia-Chung
authors: CC
authors: Hou
authors: Chi-Chang
authors: CC
authors: Huang
authors: Lie-Fen
authors: LF
authors: Shyur
mesh_terms: D000818:Animals; D020900:Echinacea / Q000737:chemistry*; D005688:Galactosamine / Q000009:adverse effects; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006505:Hepatitis / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000293:injuries; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000008:administration & dosage*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage*
chemical_list: D008070:Lipopolysaccharides; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D005688:Galactosamine; D051547:Heme Oxygenase-1; D048670:MAP Kinase Kinase 4