Rare Hybrid Dimers with Anti-Acetylcholinesterase Activities from a Safflower (Carthamus tinctorius L.) Seed Oil Cake

Safflower (Carthamus tinctorius). is commercially cultivated for vegetable oil extracted from the seeds. However, during the production process of seed oil, a large amount of the oil cake is thrown away or fermented as fertilizer to improve the homing rate of pigeons. Therefore, to solve the ecological problem and develop its new function, we investigated the chemical constituents of a safflower seed oil cake, and six new hybrid dimers, (+/-)-carthatins A-F (1-6, respectively), with a phenylpropanoid and a feruloylserotonin fused via a dihydrofuran ring, together with four known compounds, including sinapyl alcohol (7), coniferyl alcohol (8), serotobenine (9), and feruloylserotonin (10), were isolated. The extensive nudear magnetic resonance spectra, combined with electronic circular dichroism analysis and chiral high-performance liquid chromatography, allowed the complete structural assignments of (+/-)-carthatins A-F. Moreover, we evaluated their anti-acetylcholinesterase activities. Racemic carthatixis A and B (1 and 2, respectively) showed anti-acetylcholinesterase effects with IC50 values of 17.96 and 66.83 mu M, respectively. To some extent, our findings provide a new scaffold of acetylcholinesterase inhibitors, which could be beneficial for developing therapeutic molecules for the treatment of Alzheimer's disease and supporting folk application of a safflower seed oil cake.