Abstract: OBJECTIVE: To examine the neuroprotective effect of extract from Naomaitong following focal cerebral ischemia reperfusion induced by occlusion of middle cerebral artery(MCA), and to determine the biochemical alterations in urine using proton nuclear magnetic resonance spectroscopy and principal component analysis.METHODS: Wistar rats were randomly assigned tothree groups: sham-operated group, MCA focal cerebral ischemia reperfusion model group, and active extract of Naomaitong treatment group. The model was established by an improved MCA occlusion(MCAO) method. Sham-operated rats received the same surgical procedure, but without occlusion. The Naomaitong treatment group were treated with active extract from Naomaitong at a dose of3.0 g·kg-·1d-1. Brain tissues and urine samples were collected from all groups for histopathological assessment and proton nuclear magnetic resonance spectroscopy-based metabonomics, respectively.RESULTS: Hematoxylin-eosin and triphenyl tetrazolium chloride staining of brain tissues showed a significant decrease in cerebral infarction area in the Naomaitong group. In model rats, metabonomic analyses showed increased urinary levels of glutamate, taurine, trimetlylamine oxide, betaine, and glycine, and reduced levels of creatinine and creatine.Naomaitong regulated the metabolic changes by acting on multiple metabolic pathways, including glycine metabolism, glutaminolysis, transmethylation metabolism and creatinine metabolism.CONCLUSION: These data demonstrate that extract from Naomaitong is neuroprotective against focal cerebral ischemia induced by MCAO, and can alleviate biochemical changes in urinary metabolism. Metabonomics may be a useful approach for assessing the biochemical mechanisms underlying the neuroprotective actions of extract from Naomaitong.

Key words: Cerebrovascular circulation, Reperfusion, Middle cerebral artery, Principal component analysis, Metabonomics, Magnetic resonance spectroscopy, Naomaitong