Title: | Identification of 3-hydroxy-beta-damascone and related carotenoid-derived aroma compounds as novel potent inducers of Nrf2-mediated phase 2 response with concomitant anti-inflammatory activity |
Author(s): | Gerhauser C; Klimo K; Hummer W; Holzer J; Petermann A; Garreta-Rufas A; Bohmer FD; Schreier P; |
Address: | "Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany. c.gerhauser@dkfz.de" |
ISSN/ISBN: | 1613-4133 (Electronic) 1613-4125 (Linking) |
Abstract: | "Structural comparison of apple constituents with known inducers of phase two cytoprotective enzymes led to the identification of 3-hydroxy-beta-damascone and related carotenoid derived aroma compounds as potent inducers of NAD(P)H:quinone reductase (QR) activity. Damascone-related compounds were found to be more potent inducers than ionone derivatives, with CD values (concentrations required to double the specific activity of QR in Hepa1c1c7 cell culture) in the range of 1.0-5.7 microM. QR induction by 3-hydroxy-beta-damascone was shown to be mediated via transcription factor Nrf2 signaling in transient transfection experiments. We further identified aroma compounds as potent inhibitors of LPS-induced inducible nitric oxide synthase activity in Raw 264.7 cell culture. Again, damascone derivatives were most potent with half-maximal inhibitory concentration values of 1.8-7.9 microM. These results reveal previously unrecognized cancer chemopreventive potential of aroma compounds such as beta-damascenone, 3-hydroxy-beta-damascone, and related substances, which may contribute to the cancer protective efficacy of apple products and other dietary sources in animal models" |
Keywords: | "Animals Anti-Inflammatory Agents, Non-Steroidal/*pharmacology Anticarcinogenic Agents/pharmacology Cell Line Cell Survival Fruit/chemistry Humans Lipopolysaccharides/antagonists & inhibitors/pharmacology Malus/chemistry Metabolic Detoxication, Phase II Mi;" |
Notes: | "MedlineGerhauser, Clarissa Klimo, Karin Hummer, Wolfgang Holzer, Jana Petermann, Astrid Garreta-Rufas, Antonio Bohmer, Frank-D Schreier, Peter eng Research Support, Non-U.S. Gov't Germany 2009/09/16 Mol Nutr Food Res. 2009 Oct; 53(10):1237-44. doi: 10.1002/mnfr.200800492" |