Department of Food & Life Sciences, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea.
Molecules. 2012 Jul 4;17(7):8037-55. doi: 10.3390/molecules17078037.
The rhizome of ginger (Zingiber officinale Roscoe) is known to have several bioactive compounds including gingerols and shogaols which possess beneficial health properties such as anti-inflammatory and chemopreventive effects. Based on recent observations that 6-shogaol may have more potent bioactivity than 6-gingerol, we obtained a 6-shogaol-rich extract from ginger and examined its effects on the nuclear factor E2-related factor2 (Nrf2)/antioxidant response element (ARE) pathway in vitro and in vivo. 6-Shogaol-rich extract was produced by extracting ginger powder with 95% ethanol at 80 °C after drying at 80 °C (GEE8080). GEE8080 contained over 6-fold more 6-shogaol compared to the room temperature extract (GEE80RT). In HepG2 cells, GEE8080 displayed much stronger inductions of ARE-reporter gene activity and Nrf2 expression than GEE80RT. GEE8080 stimulated phosphorylations of mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. Moreover, the GEE8080-induced expressions of Nrf2 and HO-1 were attenuated by treatments of SB202190 (a p38 specific inhibitor) and LY294002 (an Akt specific inhibitor). In a mouse model, the GEE8080 decreased the diethylnitrosamine (DEN)-mediated elevations of serum aspartate transaminase and alanine transaminase as well as the DEN-induced hepatic lipid peroxidation. Inductions of Nrf2 and HO-1 by GEE8080 were also confirmed in the mice. In addition, the administration of GEE8080 to the mice also restored the DEN-reduced activity and protein expression of hepatic antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase. In conclusion, GEE8080, a 6-shogaol-rich ginger extract, may enhance antioxidant defense mechanism through the induction of Nrf2 and HO-1 regulated by p38 MAPK and PI3k/Akt pathway in vitro and in vivo.
姜（Zingiber officinale Roscoe）的根茎含有多种生物活性化合物，包括姜酚和姜烯酚，具有抗炎和化学预防等有益健康的特性。基于最近的观察结果，6-姜烯酚的生物活性可能比 6-姜酚更强，我们从姜中获得了一种富含 6-姜烯酚的提取物，并在体外和体内研究了它对核因子 E2 相关因子 2（Nrf2）/抗氧化反应元件（ARE）途径的影响。6-姜烯酚丰富的提取物是通过在 80°C 下将姜粉用 95%乙醇提取，然后在 80°C 下干燥（GEE8080）制成的。与室温提取物（GEE80RT）相比，GEE8080 中 6-姜烯酚的含量高出 6 倍以上。在 HepG2 细胞中，GEE8080 对 ARE 报告基因活性和 Nrf2 表达的诱导作用明显强于 GEE80RT。GEE8080 刺激丝裂原激活蛋白激酶（MAPK）如 ERK、JNK 和 p38 的磷酸化。此外，用 SB202190（一种 p38 特异性抑制剂）和 LY294002（一种 Akt 特异性抑制剂）处理可减弱 GEE8080 诱导的 Nrf2 和 HO-1 的表达。在小鼠模型中，GEE8080 降低了二乙基亚硝胺（DEN）介导的血清天冬氨酸转氨酶和丙氨酸转氨酶的升高以及 DEN 诱导的肝脂质过氧化。在小鼠中也证实了 GEE8080 诱导 Nrf2 和 HO-1 的表达。此外，给予 GEE8080 还恢复了 DEN 降低的肝抗氧化酶如超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶的活性和蛋白表达。总之，富含 6-姜烯酚的姜提取物 GEE8080 可能通过体外和体内 p38 MAPK 和 PI3k/Akt 途径诱导 Nrf2 和 HO-1 的表达来增强抗氧化防御机制。
