Isolation of quinone reductase (QR) inducing agents from ginger rhizome and their in vitro anti-inflammatory activity

To investigate the potential activity of ginger rhizome extracts to induce quinone reductase (QR), we performed bioactivity-guided fractionation using a murine hepatoma cell (Hepa 1c1c7) bioassay. Anti-inflammatory effects were then studied utilizing lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264.7) cells. An ethyl acetate-partitioned fraction from ethanolic extract, rich in both QR inducing potency and anti-inflammatory activity, was subjected to repeated silica gel column and preparative thin layer chromatography to yield three compounds. The three isolated compounds were [6]-shogaol, 1-dehydro-[6]-gingerdione and hexahydrocurcumin. [6]-Dehydroshogaol, a minor component in ginger rhizome, was chemically synthesized and used for comparison in the subsequent bioassay based on its excellent QR inducing potency. Results showed that [6]-dehydroshogaol had the highest ability to induce QR activity (CD = 9.23 ± 0.22 μM), followed by 1-dehydro-[6]-gingerdione (CD = 13.24 ± 0.45 μM), and then hexahydrocurcumin (CD = 68.81 ± 3.90 μM). Increasing QR activity in induced cells was associated with elevated expression of NQO-1 protein as confirmed by Western blot. [6]-Dehydroshogaol, [6]-shogaol and 1-dehydro-[6]-gingerdione were also potent inhibitors of nitric oxide (NO) synthesis in activated macrophages. Their IC50 values ranged from 5.80 ± 1.27 to 25.06 ± 4.86 μM. Hexahydrocurcumin exhibited the weakest inhibitory effect (IC50 = 304.76 ± 54.80 μM). These findings contribute to our theoretical understanding of the potential beneficial effects of consuming ginger as food and/or dietary supplement.

Research Highlights
► Isolation of quinone reductase inducing agents from ginger rhizome.
► 1-dehydro-[6]-gingerdione, 6-shogaol and hexahydrocurcumin were obtained.
► [6]-dehydroshogaol exhibited the highest activity to induce QR among four compounds.
► α,β-unsaturated carbonyl was correlated to QR inducing and anti-inflammatory activity.