Structure-activity relationships of tanshinones in activating Nrf2. A DFT study and implications for multifunctional antioxidant discovery.

A series of recent studies reveal that tanshinones, derived from the traditional Chinese herbal medicine Salvia miltiorrhiza Bunge, are promising multifunctional antioxidants by activating nuclear factor (erythroid-derived 2) - like 2 (Nrf2). It is thus of great interest to elucidate their structure-activity relationships (SAR) for Nrf2 activation. In this study, two theoretical parameters characterizing the electron-abstracting potential, namely, electron affinity (EA) and energy level of the lowest unoccupied molecular orbital (ELUMO), are calculated by a density functional theory (DFT) method. By these parameters, we provide a satisfactory explanation to the SAR oftanshinones for activating Nrf2, which is helpful to find new multifunctional antioxidants.