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 deprivatio...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.展开更多
基金supported by the 2023 Guangxi Zhuang Autonomous Region New Engineering,New Medical,New Agricultural,and New Humanities Research and Practice Project,China(No.XYK202319)the Project of Guangxi Collaborative Innovation Center of Modern Sericulture and Silk,China(No.2022GXCSSC10).
文摘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.
