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• W3022732743 abstract "Turmeric extract, a mixture of curcumin and its demethoxy (DMC) and bisdemethoxy (BDMC) isomers, is used as an anti-inflammatory preparation in traditional Asian medicine. Curcumin is considered to be the major bioactive compound in turmeric but less is known about the relative anti-inflammatory potency and mechanism of the other components, their mixture, or the reduced in vivo metabolites. We quantified inhibition of the NF-κB pathway in cells, adduction to a peptide mimicking IκB kinase β, and the role of cellular glutathione as a scavenger of electrophilic curcuminoid oxidation products, suggested to be the active metabolites. Turmeric extracts (IC50 14.5 ± 2.9 μM), DMC (IC50 12.1 ± 7.2 μM), and BDMC (IC50 8.3 ± 1.6 μM), but not reduced curcumin, inhibited NF-κB similar to curcumin (IC50 18.2 ± 3.9 μM). Peptide adduction was formed with turmeric and DMC but not with BDMC, and this correlated with their oxidative degradation. Inhibition of glutathione biosynthesis enhanced the activity of DMC but not BDMC in the cellular assay. These findings suggest that NF-κB inhibition by curcumin and DMC involves their oxidation to reactive electrophiles, whereas BDMC does not require oxidation. Because it has not been established whether curcumin undergoes oxidative transformation in vivo, oxidation-independent BDMC may be a promising alternative to test in clinical trials." @default.
• W3022732743 created "2020-05-13" @default.
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• W3022732743 date "2020-05-07" @default.
• W3022732743 modified "2023-10-17" @default.
• W3022732743 title "Mechanistic Differences in the Inhibition of NF-κB by Turmeric and Its Curcuminoid Constituents" @default.
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• W3022732743 doi "https://doi.org/10.1021/acs.jafc.0c02607" @default.
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