Pinocembrin attenuates hippocampal inflammation, oxidative perturbations and apoptosis in a rat model of global cerebral ischemia reperfusion

Background: Pinocembrin is a major flavonoid molecule isolated from honey and propolis. It has versatile pharmacological and biological activities including antimicrobial, anti-inflammatory, antioxidant, and anticancer activities as well as neuroprotective effects against cerebral ischemic injury. The purpose of the current study was to determine the possible mechanisms of neuroprotection elicited by pinocembrin with specific emphasis on chronic prophylactic use before the induction of global cerebral ischemia reperfusion. Methods: Global cerebral ischemia-reperfusion (I/R) was induced by bilateral carotid artery occlusion for 15 min followed by 60 min reperfusion period. Animals were randomly allocated into 3 groups (n = 28): Sham operated, I/R control and rats treated with pinocembrin (10 mg/kg, po) daily for 7 days then I/R was induced 1 h after the last dose of pinocembrin. After reperfusion rats were killed by decapitation, brains were removed and both hippocampi separated and the following biochemical parameters were estimated; lactate dehydrogenase activity, oxidative stress markers (lipid peroxides, nitric oxide and reduced glutathione), inflammatory markers (myeloperoxidase, tumor necrosis factoralpha, nuclear factor kappa-B, interleukin-6 and interleukin-10), apoptotic biomarkers (caspase 3 and cytochrome C), neurotransmitters (glutamate, gamma aminobutyric acid) and infarct size were assessed. Results: Pinocembrin ameliorated damage induced by I/R through suppressing oxidative stress, inflammatory and apoptotic markers as well as mitigating glutamate and lactate dehydrogenase activity. One of the more significant findings to emerge from this study is that pinocembrin normalized the infarct size elevated by I/R. Conclusions: Pinocembrin showed a neuroprotective effects through antioxidant, anti-inflammatory and antiapoptotic mechanisms. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.