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

作者：Shen, Hongmei; Yuan, Ying; Ding, Fei; Hu, Nan; Liu, Jie; Gu, Xiaosong^*

来源：Journal of Neuroscience Research, 2010, 88(3): 669-676.

DOI：10.1002/jnr.22221

• Achyranthes bidentata polypeptides
• middle cerebral artery occlusion
• N-methyl-D-aspartate receptors
• mitochondrial apoptosis pathway

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.

• 出版日期2010-2-15
• 单位南通大学