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.

6-Shogaol, a dehydrated form of 6-gingerol, is a minor component in ginger (Zingiber officinale Roscoe) and has recently been reported to have more potent bioactivity than 6-gingerol. Based on the thermal instability of gingerols (their dehydration to corresponding shogaols at high temperature), we aimed to develop an optimal process to maximize the 6-shogaol content during ginger extraction by modulating temperature and pH. Fresh gingers were dried under various conditions: freeze-, room temperature (RT)- or convection oven-drying at 60 or 80°C, and extracted by 95% ethanol at RT, 60 or 80°C. The content of 6-shogaol was augmented by increasing both drying and extraction temperatures. The highest production of 6-shogaol was achieved at 80°C extraction after drying at the same temperature and the content of 6-shogaol was about 7-fold compared to the lowest producing process by freezing and extraction at RT. Adjustment of pH (pH 1, 4, 7 and 10) for the 6-shogaol-richest extract (dried and extracted both at 80°C) also affected the chemical composition of ginger and the yield of 6-shogaol was maximized at the most acidic condition of pH 1. Taken together, the current study shows for the first time that a maximized production of 6-shogaol can be achieved during practical drying and extraction process of ginger by increasing both drying and extracting temperatures. Adjustment of pH to extraction solvent with strong acid also helps increase the production of 6-shogaol. Our data could be usefully employed in the fields of food processing as well as nutraceutical industry.

We investigated the cellular and molecular mechanisms mediating the effects of Angelica gigas Nakai extract (AGNE) through the mitogen-activated protein kinases (MAPKs)/NF-κB pathway using in vitro and in vivo atopic dermatitis (AD) models. We examined the effects of AGNE on the expression of proinflammatory cytokines and chemokines in human mast cell line-1 (HMC-1) cells. Compound 48/80-induced pruritus and 2,4-dinitrochlorobenzene- (DNCB-) induced AD-like skin lesion mouse models were also used to investigate the antiallergic effects of AGNE. AGNE reduced histamine secretion, production of proinflammatory cytokines including interleukin- (IL-) 1β, IL-4, IL-6, IL-8, and IL-10, and expression of cyclooxygenase- (COX-) 2 in HMC-1 cells. Scratching behavior and DNCB-induced AD-like skin lesions were also attenuated by AGNE administration through the reduction of serum IgE, histamine, tumor necrosis factor-α (TNF-α), IL-6 levels, and COX-2 expression in skin tissue from mouse models. Furthermore, these inhibitory effects were mediated by the blockade of the MAPKs and NF-κB pathway. The findings of this study proved that AGNE improves the scratching behavior and atopy symptoms and reduces the activity of various atopy-related mediators in HMC-1 cells and mice model. These results suggest the AGNE has a therapeutic potential in anti-AD.

The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.