Protective Effect Against Hydroxyl Radical-induced DNA Damage and Antioxidant Mechanism of [6]-gingerol: A Chemical Study

Abstract

[6]-Gingerol is known as the major bioactive constituent of ginger. In the study, it was observed to effectively protect against <TEX>${\bullet}OH$</TEX>-induced DNA damage (<TEX>$IC_{50}$</TEX> <TEX>$328.60{\pm}24.41{\mu}M$</TEX>). Antioxidant assays indicated that [6]-gingerol could efficiently scavenge various free radicals, including <TEX>${\bullet}OH$</TEX> radical (<TEX>$IC_{50}$</TEX> <TEX>$70.39{\pm}1.23{\mu}M$</TEX>), <TEX>${\bullet}O_2{^-}$</TEX> radical (<TEX>$IC_{50}$</TEX> <TEX>$228.40{\pm}9.20{\mu}M$</TEX>), <TEX>$DPPH{\bullet}$</TEX>radical (<TEX>$IC_{50}$</TEX> <TEX>$27.35{\pm}1.44{\mu}M$</TEX>), and <TEX>$ABTS{^+}{\bullet}$</TEX>radical (<TEX>$IC_{50}$</TEX> <TEX>$2.53{\pm}0.070{\mu}M$</TEX>), and reduce <TEX>$Cu^{2+}$</TEX> ion (<TEX>$IC_{50}$</TEX> <TEX>$11.97{\pm}0.68{\mu}M$</TEX>). In order to investigate the possible mechanism, the reaction product of [6]-gingerol and <TEX>$DPPH{\bullet}$</TEX> radical was further measured using HPLC combined mass spectrometry. The product showed a molecular ion peak at m/z 316 <TEX>$[M+Na</TEX><TEX>]</TEX><TEX>^+$</TEX>, and diagnostic fragment loss (m/z 28) for quinone. On this basis, it can be concluded that: (i) [6]-gingerol can effectively protect against <TEX>${\bullet}OH$</TEX>-induced DNA damage; (ii) a possible mechanism for [6]-gingerol to protect against oxidative damage is <TEX>${\bullet}OH$</TEX> radical scavenging; (iii) [6]-gingerol scavenges <TEX>${\bullet}OH$</TEX> radical through hydrogen atom (<TEX>$H{\bullet}$</TEX>) transfer (HAT) and sequential electron (e) proton transfer (SEPT) mechanisms; and (iv) both mechanisms make [6]-gingerol be oxidized to semi-quinone or quinone forms.