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

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.

A 3-hydroxy %-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals

“…These carbonyl compounds have diverse biological activities by reacting with sulfhydryl groups of target proteins. Various phytochemicals and medicines with an ␣ , ␤ -unsaturated carbonyl structure were reported to have biological activity such as anti-tumor, anti-viral, and anti-infl ammatory activities (42)(43)(44). In the present study, three oxidative metabolites of xanthophylls were found to suppress the NO production by mouse macrophage RAW 264 cells stimulated with LPS.…”

Formation of Damascenone and its Related Compounds from Carotenoids in Tea

“…For example, they can act as antioxidants or exhibit antimicrobial properties (reviewed by Goff and Klee, 2006). It was found that these compounds can both up-regulate the phase 2 cytoprotective enzymes and inhibit the induction of pro-inflammatory enzymes (Gerhäuser et al, 2009). It was found that these compounds can both up-regulate the phase 2 cytoprotective enzymes and inhibit the induction of pro-inflammatory enzymes (Gerhäuser et al, 2009).…”

“…Preliminary studies highlight the fact that the varied chemical natures of these compounds significantly influence their biological activities (Gerhäuser et al, 2009). Moreover, systematic studies are needed to elucidate the specific chemical properties of each species.…”

Carotenoids and Norisoprenoids as Carotenoid Degradation Products in Pandan Leaves (Pandanus amaryllifoliusRoxb.)

“…[16] Apart from their role as aroma impact compounds, several norisoprenoids (β-ionone, β-damascenone, and 3-hydroxy-β-damascone) show health-related properties, such as anticarcinogenic activity. [17,18] Pandan leaves are a promising source of natural colorant, as well as a natural flavor precursor. In this work, a general screening of norisoprenoids and carotenoids as their precursors was performed.…”