title: Glutathione conjugation attenuates biological activities of 6-dehydroshogaol from ginger.
abstract: 6-Dehydroshogaol (6-DHSG) is a bioactive α,β-unsaturated carbonyl compound isolated from fresh ginger with anti-inflammatory and phase II enzyme inducing activities. Here we describe the glutathione (GSH)-dependent metabolism and the effect of this metabolic transformation on the biological activities of 6-DHSG. Compared with other ginger compounds, such as 6-gingerol and 6-shogaol, 6-DHSG showed the most potent anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The biological activities of 6-DHSG were attenuated by sulfhydryl antioxidants such as glutathione (GSH) or N-acetyl cysteine (NAC), but not ascorbic acid (ASC). 6-DHSG was metabolised by GSH to form a GSH conjugate (GS-6-DHSG) in RAW 264.7 cells, via a potential mechanism involving the catalytic activity of glutathione-S-transferase (GST). GS-6-DHSG showed reduced biological activities compared with 6-DHSG in multiple biological assays. Together, these results indicate that GSH conjugation attenuates the biological activities of 6-DHSG and other α,β-unsaturated carbonyl compounds.
authors.affiliation: Department of Food Science, University of Wisconsin, 1605 Linden Dr., Madison, WI 53706, USA. gdzhang@ucdavis.edu
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.forename: Viriya
authors.initials: V
authors.lastname: Nitteranon
authors.forename: Lok Yan
authors.initials: LY
authors.lastname: Chan
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Parkin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D002396:Catechols / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D005233:Fatty Alcohols / Q000737:chemistry / Q000378:metabolism*; D020939:Zingiber officinale / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D002396:Catechols; D005233:Fatty Alcohols; D010936:Plant Extracts; C007845:gingerol; D005982:Glutathione Transferase; D005978:Glutathione