Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, Republic of China.
J Agric Food Chem. 2011 Nov 23;59(22):11966-74. doi: 10.1021/jf202958r. Epub 2011 Oct 25.
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.
本研究旨在探讨从紫锥菊根部分离得到的主要丙烯酰胺十二碳-2E、4E、8Z、10Z(E)-四烯酸异丁酰胺（Alk-8/9）对脂多糖/半乳糖胺（LPS/D-GalN）诱导的小鼠急性暴发性肝炎的抗炎和保肝作用。结果表明，Alk-8/9 可剂量依赖性诱导 LPS 刺激的小鼠巨噬细胞血红素加氧酶（HO）-1 蛋白表达，这可能是通过增加 SAPK/JNK 磷酸化、c-jun 蛋白表达和磷酸化以及转录因子 AP-1 结合的 DNA 活性来调节 JNK 介导的途径。HO-1 抑制剂或 CO 清除剂显著逆转了 Alk-8/9 对 TNF-α 表达的抑制作用，而 N-乙酰-L-半胱氨酸则观察到减少了 LPS 处理的巨噬细胞中 Alk-8/9 诱导的 HO-1 表达。此外，Alk-8/9 显著诱导 c-jun 和 HO-1 蛋白表达，并抑制 LPS/d-GalN 处理小鼠的血清转氨酶活性、TNF-α 表达和肝组织肝细胞损伤。本文提出了一种新的应用，即作为一种保肝剂，使用紫锥菊，一种最畅销的草药补充剂。
