Enhancement of Antioxidant Activity of Isorosmanol in Aqueous Micellar Solution by a Cysteine Thiol

This study investigated the enhancement of antioxidant activity of rosemary diterpene polyphenols in the presence of thiols. The antioxidant capacity was assessed by measuring the inhibition of lipid oxidation in an aqueous micellar system as a model for many foods containing water. The antioxidant activity of major diterpene polyphenols [carnosic acid (CA), carnosol (CAR), rosmanol (ROS), and isorosmanol (ISO)] under the conditions in the presence or absence of cysteine thiol (1 or 2 mol equiv) was examined at 0.63 mM for 5–8 days. Only CAR and ISO exhibited a significant enhancement in antioxidant activity in the presence of the thiol, with ISO demonstrating a greater effect. To investigate the mechanism underlying the enhancement by ISO, time-course analysis by high-performance liquid chromatography (HPLC) and structural characterization of a key reaction product were first conducted. Subsequently, HPLC and rapid ultraviolet–visible (UV–vis) spectral scanning were employed to examine the reactions of quinone derivatives from ISO and ROS, confirming the markedly higher reactivity of the ISO quinone with the thiol. These experimental findings were further examined by density functional theory (DFT) calculations, which elucidated a reaction mechanism consistent with the notable enhancement in antioxidant activity observed for ISO.