Pinocembrin protects rat brain against oxidation and apoptosis induced by ischemia-reperfusion both in vivo and in vitro.
Pinocembrin is one of the flavonoids at the highest concentration in propolis. In this study, we investigated the neuroprotective effect of pinocembrin on ischemia/reperfusion and ischemia/reperfusion-like insults. Protection by pinocembrin was studied at the in vivo level using a model of middle cerebral artery occlusion and reperfusion in rats. Pinocembrin was administrated at the start of reperfusion. Pinocembrin markedly increased rat viability, reduced infarct volumes and neurological deficit scores in all treatment groups. Primary cortical neuronal cultures were subjected to oxygen-glucose deprivation/reoxygenation, a model of ischemia/reperfusion-like injury, and treated with pinocembrin at the start of reoxygenation. Neuronal survival rates were increased, LDH release was decreased and both neurite length and apoptosis were alleviated when pinocembrin was present during reoxygenation, and this protection was associated with the reduction of reactive oxygen species, nitric oxide and neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS), and an increase of glutathione. Moreover, DNA laddering was decreased in treatment groups of pinocembrin. Caspase-3 protein was down-regulated and PARP degradation was alleviated after pinocembrin treatments. Our results suggest that pinocembrin may be a novel therapeutic strategy to reduce cerebral ischemia/reperfusion injury, and may act by the anti-oxidative and anti-apoptotic effects.
Liu
Rui
R
National Centre for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Gao
Mei
M
Yang
Zhi-Hong
ZH
Du
Guan-Hua
GH
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D044950:Flavanones / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018709:Statistics, Nonparametric
D044950:Flavanones; D018696:Neuroprotective Agents; D009569:Nitric Oxide; C016063:pinocembrin