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.
Highlights
The cellular defense mechanism through induction of phase II detoxifying and/or antioxidant stress responsive genes is extremely important in protection of cells/tissues against both toxic chemicals and the resulting oxidative stress [1,2]
The DEN-attenuated heme oxygenase-1 (HO-1) expression was restored by GEE8080. These data suggest a possible involvement of nuclear factor E2-related factor2 (Nrf2) and Nrf2-mediated HO-1 expression by GEE8080 which may contribute to hepatic protection against DEN toxicity in mice. 6-Gingerol, a major constituent in ginger, has been shown to have hepatoprotective effects in acetaminophen-induced hepatotoxic mice through lowering hepatic markers such as aspartate trasaminase (AST) and alanine transaminase (ALT) [50]
Our study reports for the first time the hepatoprotective activity of 6-shogaol-rich ginger extract via Nrf2/antioxidant response element (ARE)-mediated antioxidant defense mechanism
Summary
The cellular defense mechanism through induction of phase II detoxifying and/or antioxidant stress responsive genes is extremely important in protection of cells/tissues against both toxic chemicals and the resulting oxidative stress [1,2]. By phenolic antioxidants and other naturally occurring cancer chemopreventive agents [1,3] These enzymes protect cells and/or tissues from carcinogens that can initiate carcinogenic process [1,4,5]. The rhizome of ginger (Zingiber officinale Roscoe) originated in Southeast Asia and is nowadays widely spread around the World It has been reported as a traditional medicinal herb for thousands of year to treat many diseases such as gastrointestinal, stomachic, and rheumatic disorders [7]. We applied this observation to a real extraction process, produced a 6-shogaol-rich extract, and evaluated its regulatory roles in cellular defense mechanisms, in particular its ability to induce Nrf2/ARE-mediated gene expressions in cells and an animal model
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
