Phenylpropanoid dimers from Chrysanthemum indicum with antioxidant effects via activating the Nrf2 signaling pathway

Five phenylpropanoid dimers chrysanthephenyls A-E, with the 1-O-1'-type (1) and 1-O-2'-type (2-5) ether bond linking modes, were isolated from the aerial parts of Chrysanthemum indicum. Among them, chrysanthephenyls D and E were two pairs of enantiomers, and chrysanthephenyl E was further resolved into its enantiomers (+)-chrysanthephenyl E and (-)-chrysanthephenyl E via chiral-phase HPLC. Their structures were characterized on the basic analysis of the spectroscopic techniques (IR, HRESIMS, 1D and 2D NMR), and their absolute configurations were determined by DP4+ NMR analysis and ECD calculation method. The antioxidant activity of chrysanthephenyls A-E was determined by measuring their free radical scavenging effects using the trolox equivalent antioxidant activity (TEAC) assay, and chrysanthephenyls D and E showed 17 and 15 times better activity respectively than that of the positive control trolox. Moreover, a mechanistic study revealed that the potential antioxidant activity of chrysanthephenyl D decreased the level of reactive oxygen species (ROS) mediated via activating nuclear factor E2-related factor 2 (Nrf2) and its downstream oxidases.