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

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