6-shogaol-rich extract from ginger up-regulates the antioxidant defense systems in cells and mice

Molecules. 2012 Jul 4;17(7):8037-55. doi: 10.3390/molecules17078037.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / metabolism*
  • Aspartate Aminotransferases / blood
  • Catechols / pharmacology*
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Diethylnitrosamine
  • Genes, Reporter / genetics
  • Ginger / chemistry*
  • Heme Oxygenase-1 / metabolism
  • Hep G2 Cells
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Luciferases / metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Response Elements / genetics
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Up-Regulation / drug effects*

Substances

  • Antioxidants
  • Catechols
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Plant Extracts
  • Thiobarbituric Acid Reactive Substances
  • Diethylnitrosamine
  • shogaol
  • Luciferases
  • Heme Oxygenase-1
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases