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6-Shogaol-Rich Extract from Ginger Up-Regulates the Antioxidant Defense Systems in Cells and Mice
Department of Food & Life Sciences, College of Biomedical Science & Engineering, Inje University, Gimhae 621-749, Korea
Department of Pharmacy, Kyungsung University, Busan 808-736, Korea
Department of Food Science & Nutrition, Dong-A University, Busan 604-714, Korea
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 21 May 2012; in revised form: 23 June 2012 / Accepted: 2 July 2012 / Published: 4 July 2012
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.
Keywords: ginger; 6-shogaol; Nrf2; antioxidant response element (ARE); antioxidant defense; MAPK; chemoprevention; cytoprotection; hemeoxygenase 1; antioxidant enzyme
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Bak, M.-J.; Ok, S.; Jun, M.; Jeong, W.-S. 6-Shogaol-Rich Extract from Ginger Up-Regulates the Antioxidant Defense Systems in Cells and Mice. Molecules 2012, 17, 8037-8055.
Bak M-J, Ok S, Jun M, Jeong W-S. 6-Shogaol-Rich Extract from Ginger Up-Regulates the Antioxidant Defense Systems in Cells and Mice. Molecules. 2012; 17(7):8037-8055.
Bak, Min-Ji; Ok, Seon; Jun, Mira; Jeong, Woo-Sik. 2012. "6-Shogaol-Rich Extract from Ginger Up-Regulates the Antioxidant Defense Systems in Cells and Mice." Molecules 17, no. 7: 8037-8055.