Is natural fraxin an overlooked radical scavenger?

Fraxin (FX) (7-hydroxy-6-methoxycoumarin 8-glucoside) is a typical natural product of the coumarin family. This compound was shown to protect endothelial cells from oxidative stress; however, the nature of its antioxidant properties is still ambiguous. In this study, we report on a systematic evaluation of the radical scavenging activity of FX using a two-tier protocol based on thermodynamic and kinetic calculations. The results show that FX has moderate activity in the aqueous physiological environment against a range of radicals including HO center dot, CCl3O center dot, CCl3OO center dot, NO2, SO4 center dot, N-3(center dot) and HOO center dot. The latter was examined in detail due to the prevalence of HOO center dot as a source of oxidative stress in biological systems. HOO center dot scavenging activity was promising in the gas phase but low in physiological environments with k(overall) = 1.57 x 10(6), 3.13 x 10(2) and 2.68 x 10(3) M-1 s(-1) in the gas phase, pentyl ethanoate and water solvents, respectively. The formal hydrogen transfer mechanism at the O7-H bond dominates the hydroperoxyl radical scavenging of FX in the nonpolar media, whereas, in the polar environment, the activity is exerted by the single electron transfer mechanism of the anion state. This activity falls behind typical antioxidants such as Trolox, ascorbic acid, and trans-resveratrol under the studied conditions. Thus FX may have multiple health benefits, but it is not an outstanding natural antioxidant.

Automated summary

The study systematically evaluated the radical scavenging activity of FX and found it to have moderate activity against various radicals in different environments. FX showed promising scavenging activity against HOO center dot in the gas phase but lower activity in physiological environments. Its antioxidant activity falls behind typical antioxidants under the studied conditions.