title: 6-shogaol-rich extract from ginger up-regulates the antioxidant defense systems in cells and mice.
abstract: 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.
authors: Department of Food & Life Sciences, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea. redapplemj@hanmail.net
authors: Min-Ji
authors: MJ
authors: Bak
authors: Seon
authors: S
authors: Ok
authors: Mira
authors: M
authors: Jun
authors: Woo-Sik
authors: WS
authors: Jeong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000097:blood; D002396:Catechols / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004052:Diethylnitrosamine; D017930:Genes, Reporter / Q000235:genetics; D020939:Zingiber officinale / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D002396:Catechols; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; D004052:Diethylnitrosamine; C040115:shogaol; D008156:Luciferases; D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases