Study on Derivatization and Biological Activity of Natural Product Daidzein

A new class of Daidzein derivatives were developed,and their protective effects on neuronal cells and their mechanisms were examined.The protective effects of Daidzein derivatives against oxygen and glucose deprivation/reoxygenation(OGD/R)injury in HT22 cells were evaluated via a Cell Counting Kit 8(CCK-8)assay.Biomarkers associated with ferroptosis,including changes in reactive oxygen species(ROS);lipid peroxidation,ferrous ion(Fe^(2+));glutathione(GSH);superoxide dismutase(SOD);malondialdehyde(MDA)levels,were detected via fluorescent probes and specific kits.In addition,the protein expression levels of glutathione peroxidase 4(GPX4);recombinant solute carrier family 7,member 11(SLC7A11 or xCT);nuclear Factor 2(Nrf2)were analyzed via Western blotting.The newly synthesized Daidzein derivative outperforms not only its parent compound,especially derivative 3,in improving the viability of OGD/R-treated HT22 cells but also edaravone,a positive control drug.This study further revealed the mechanism of action of derivative 3:reducing the level of ROS and lipid peroxidation induced by OGD/R in HT22 cells,restoring SOD and GSH activities,reducing MDA and Fe2+accumulation,and increasing the protein expression of GPX4,xCT and Nrf2.Derivative 3 has significant neuroprotective effects,and its mechanism may involve activating the Nrf2/xCT/GPX4 pathway and inhibiting neuronal ferroptosis.This study provides a new perspective for neuroprotection research and a direction for drug development.