Neuroprotective Effects of a Standardized Extract of Diospyros kaki Leaves on MCAO Transient Focal Cerebral Ischemic Rats and Cultured Neurons Injured by Glutamate or Hypoxia

Abstract

Naoxinqing (NXQ, a standardized extract of Diospyros kaki leaves) is a patented and approved drug of Traditional Chinese Medicine (TCM) used for the treatment of apoplexy syndrome for years in China, but its underlying mechanism remains to be further elucidated. The present study investigates the effects of NXQ against focal ischemia/reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats and against glutamate-induced cell injury of hippocampal neurons as well as against hypoxia injury of cortical neurons. Oral administrations of NXQ at 20, 40, 80 mg/kg/day for 7 days (3 days before MCAO and 4 days after MCAO) significantly reduced the lesion of the insulted brain hemisphere and improved the neurological behavior of the rats. In primary rat hippocampal neuron cultures, treatment with NXQ at 5 - 20 μg mL concentration protects the neurons against glutamate-induced excitotoxic death in a dose-dependent manner. In primary rat cerebral cortical neuron cultures, pretreatment with 5 - 100 μg/mL NXQ also attenuates hypoxia-reoxygen induced neuron death and apoptosis in a dose-dependent manner. These results suggest that NXQ significantly protects the rats from MCAO ischemic injury in vivo and the hippocampal neurons from glutamate-induced excitotoxic injury as well as cortical neurons from hypoxia injury in vitro by synergistic mechanisms involving its antioxidative effects.

Abbreviations

NXQ:Naoxinqing

CNS:central nervous system

MCAO:middle cerebral artery occlusion

I/R:ischemia and reperfusion

Key words

Naoxinqing - Diospyros kaki L. - CNS pharmacology - neuroprotection - middle cerebral artery occlusion - ischemia and reperfusion - glutamate - hypoxia

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