Theoretical study of the antioxidant mechanism of chrysin and its metabolites – a computational approach

Flavonoid chrysin, obtained from different plants, has different pharmacological property, due to its antioxidative effects. But the poor bioavailability of chrysin limits its therapeutics application. In systemic circulation, chrysin can be transported by binding with serum albumin protein. Furthermore, in hepatic circulation, two chrysin metabolites e.g. chrysin-7-O-glucuronide (C7G) and chrysin-7-O-sulphate (C7S) are formed by biotransformation process in liver. By using computational methods like density functional theory (DFT) study, the antioxidant potential of these four compounds has been investigated. In this study, both the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) have been identified by using Gaussian software. The energies of these orbitals, as well as the energy gap between HOMO and LUMO, have been calculated. Using these calculations, it can be concluded that chrysin in its bound form with human serum albumin, is the best antioxidant among these four compounds. Since, it has the lowest energy gap between the calculated HOMO and LUMO. In this bound form, the cinnamoyl group present in chrysin molecule participates in the charge transfer event. The antioxidant activity by donating electrons to scavenge the free radicles, has been explained for chrysin and its derivatives. Global descriptive parameters, which describe the reactivity and stability of molecules, are calculated to highlight the electron or proton donation/acceptance of these four compounds. Antioxidant efficiency correlates strongly with electron-donating ability and stability of the resulting radical. The albumin bound chrysin is considered as best antioxidant among these four compounds for the three types of antioxidation reaction mechanisms. This finding will help us to overcome the problem regarding poor bioavailability of chrysin during its performance as antioxidant.