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Pharmacol Biochem Behav. 2015 Aug;135:199-209. doi: 10.1016/j.pbb.2015.06.009. Epub 2015 Jun 15.

Orally administrated pterostilbene attenuates acute cerebral ischemia-reperfusion injury in a dose- and time-dependent manner in mice.

Author information

1
Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China.
2
Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China. Electronic address: xinjin@xmu.edu.cn.

Abstract

Pterostilbene (3,5-dimethoxy-4-hydroxystilbene) is a component of blueberry. It has been reported that long-term treatment with blueberry has a neuroprotective effect. However, it has not been reported whether pterostilbene is effective in attenuating cerebral ischemia/reperfusion (I/R) injury. In the present study, focal cerebral ischemia was induced by middle cerebral artery occlusion for 90min followed by reperfusion. To observe the dose-dependent effect, pterostilbene (2.5-80mg/kg, ig) was administered for 3days before ischemia. To determine the time-dependent effect, pterostilbene (10mg/kg, ig) was administered as a single dose at 0, 1, or 3h after reperfusion. Twenty-four hours after I/R, pterostilbene dose-dependently improved neurological function, reduced brain infarct volume, and alleviated brain edema. The most effective dose was 10mg/kg; the therapeutic time window was within 1h after I/R and treatment immediately after reperfusion showed the best protective effect. The protective effect is further confirmed by the results that post-ischemic treatment with pterostilbene (10mg/kg) significantly improved motor function, alleviated blood brain barrier disruption, increased neurons survival and reduced cell apoptosis in cortical penumbra after cerebral I/R. We also found that pterostilbene (10mg/kg) significantly reversed the increased content of malondialdehyde and the decreased activity of superoxide dismutase in the ipsilateral hemisphere. Furthermore, pterostilbene decreased the oxidative stress markers 4-hydroxynonenal and 8-hydroxyguanosine positive cells in the cortical penumbra. All these findings indicate that pterostilbene dose- and time-dependently exerts a neuroprotective effect against acute cerebral I/R injury. This neuroprotective effect of pterostilbene may be associated with its inhibition of oxidative stress and subsequent neuronal apoptosis in the cortical penumbra.

KEYWORDS:

Apoptosis; Cerebral ischemia/reperfusion; Mice; Oxidative stress; Pterostilbene

PMID:
26086685
DOI:
10.1016/j.pbb.2015.06.009
[Indexed for MEDLINE]

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