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Identification of 3‐hydroxy‐β‐damascone and related carotenoid‐derived aroma compounds as novel potent inducers of Nrf2‐mediated phase 2 response with concomitant anti‐inflammatory activity
Author(s) -
Gerhäuser Clarissa,
Klimo Karin,
Hümmer Wolfgang,
Hölzer Jana,
Petermann Astrid,
GarretaRufas Antonio,
Böhmer FrankD.,
Schreier Peter
Publication year - 2009
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200800492
Subject(s) - aroma , concomitant , ionone , inducer , chemistry , carotenoid , identification (biology) , pharmacology , biochemistry , stereochemistry , biology , medicine , food science , gene , botany
Structural comparison of apple constituents with known inducers of phase two cytoprotective enzymes led to the identification of 3‐hydroxy‐β‐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 μM. QR induction by 3‐hydroxy‐β‐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 μM. These results reveal previously unrecognized cancer chemopreventive potential of aroma compounds such as β‐damascenone, 3‐hydroxy‐β‐damascone, and related substances, which may contribute to the cancer protective efficacy of apple products and other dietary sources in animal models.