Echinacea Alkamides Prevent Lipopolysaccharide/d-Galactosamine- Induced Acute Hepatic Injury through JNK Pathway-Mediated HO-1 Expression

Chia-Chung Hou, Chi-Chang Huang, and Lie-Fen Shyur*
Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, Republic of China
Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan County 333, Taiwan, Republic of China
J. Agric. Food Chem., 2011, 59 (22), pp 11966–11974
DOI: 10.1021/jf202958r
Publication Date (Web): October 10, 2011
Copyright © 2011 American Chemical Society
Phone/fax: +886 2 26515028. E-mail: lfshyur@ccvax.sinica.edu.tw.

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.

Keywords:

Echinacea; alkamide; heme oxygenase-1; JNK pathway; fulminant hepatitis

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History

  • Published In Issue November 23, 2011
  • Article ASAPOctober 25, 2011
  • Just Accepted ManuscriptOctober 10, 2011
  • Received: July 26, 2011
    Revised: October 08, 2011
    Accepted: October 10, 2011

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