Achyranthes bidentata polypeptides confer neuroprotection through inhibition of reactive oxygen species production, Bax expression, and mitochondrial dysfunction induced by overstimulation of N-methyl-D-aspartate receptors.
Achyranthes bidentata polypeptides (ABPP), the important constituents separated from the aqueous extract of Achyranthes bidentata, have been shown to attenuate N-methyl-D-aspartate (NMDA)-induced cell apoptosis in cultured hippocampal neurons through differential modulation of NR2A- and NR2B-containing NMDA receptors. The present study sought to investigate the possible mechanism underlying the neuroprotective effect of ABPP on NMDA-induced cell death. Western blot analysis and colorimetric enzymatic assay demonstrated that ABPP pretreatment inhibited NMDA-induced increase of Bax protein expression or caspase-3 activity in cultured hippocampal neurons. Fluorescence measurements after staining with 2,7-dichlorofluorescin diacetate and rhodamine 123 showed that ABPP treatment also reversed NMDA-induced intracellular radical oxygen species (ROS) elevation and mitochondrial membrane potential depression in cultured hippocampal neurons. Furthermore, the in vivo effects of ABPP on cerebral neuronal damage during focal ischemia-reperfusion were also investigated. In rat middle cerebral artery occlusion (MCAO) model, ABPP attenuated the increase in the neurological deficit and cerebral infarction induced by focal ischemia-reperfusion, showing in vivo neuroprotective effects. The results collectively suggest that ABPP might exert neuroprotective actions through inhibiting Bax protein expression, caspase-3 activity, ROS production, and mitochondrial dysfunction that are all caused by overstimulation of NMDA receptors.
Shen
Hongmei
H
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, People's Republic of China.
Yuan
Ying
Y
Ding
Fei
F
Hu
Nan
N
Liu
Jie
J
Gu
Xiaosong
X
D029044:Achyranthes; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D018696:Neuroprotective Agents; D010455:Peptides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3