Echinacea alkamides prevent lipopolysaccharide/D-galactosamine-induced acute hepatic injury through JNK...

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.