Neuroprotective effects of formononetin against NMDA-induced apoptosis in cortical neurons.
Formononetin (FMNT) is an isoflavone found in many herbs including Trifolium pratense L., Spatholobus suberectus Dunn., and Astragalus mongholicus Bunge. The purpose of this study is to investigate pharmacological properties of FMNT on neurotoxicity induced by N-methyl-D-asparate (NMDA) in primary-cultured cortical neurons. The cell viability was significantly decreased after exposure to NMDA (200 μM) for 40 min. Pretreatment of FMNT (10 μM) for 12 h significantly attenuated the cell loss induced by NMDA exposure. Flow cytometry analysis revealed that treatment of FMNT attenuated the number of apoptotic cells, especially the early phase apoptotic cells, induced by NMDA exposure. Western blot analysis showed that FMNT regulated the expression of apoptosis-related proteins by increasing the levels of Bcl-2 and pro-caspase-3 and decreasing the levels of Bax and caspase-3. These findings demonstrate that FMNT is capable of protecting neurons from NMDA-evoked excitotoxic injury and has a potential perspective to the clinical treatment for neurodegenerative disorders in central nervous system.
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Zhen
Z
Tian
Shui-Bing
SB
Liu
Yu-Cai
YC
Wang
Xiao-Qiang
XQ
Li
Lian-He
LH
Zheng
Ming-Gao
MG
Zhao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000166:cytology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D007529:Isoflavones; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; C007768:formononetin; D016202:N-Methylaspartate; C505409:Casp3 protein, mouse; D053148:Caspase 3
N-methyl-D-asparate; apoptosis; formononetin; isoflavone