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

Pinocembrin attenuates hippocampal inflammation, oxidative perturbations and apoptosis in a rat model of global cerebral ischemia reperfusion
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DOI:
10.1016/j.pharep.2014.08.014
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发表时间:
2015-02-01
影响因子:
4.4
通讯作者:
Attia, Amina S.
Attia, Amina S.
中科院分区:
医学3区
文献类型:
--
作者:
Saad, Muhammed A.;Salam, Rania M. Abdel;Attia, Amina S.

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背景:松属素是从蜂蜜和蜂蜜中分离的主要黄酮类化合物。它具有多种药理学和生物学活性,包括抗微生物、抗炎、抗氧化和抗癌活性,以及对脑缺血损伤的神经保护作用。目前的研究的目的是确定可能的机制pinocembrin引起的神经保护,特别强调慢性预防性使用诱导前的全脑缺血reperfusion.Methods:全脑缺血再灌注(I/R)诱导双侧颈动脉闭塞15分钟,然后60分钟的再灌注期。将动物随机分为3组(n = 28):假手术组、I/R对照组和每天用松属素(10 mg/kg,po)处理大鼠7天,然后在最后一次给药松属素后1 h诱导I/R。再灌注后断头处死大鼠,取脑,分离双侧海马,测定以下生化指标;乳酸脱氢酶活性,氧化应激标志物(脂质过氧化物、一氧化氮和还原型谷胱甘肽)、炎症标志物(髓过氧化物酶、肿瘤坏死因子α、核因子κ-B、白细胞介素-6和白细胞介素-10)、凋亡生物标志物结果:松属素通过抑制氧化应激、炎症和凋亡标志物以及降低谷氨酸和乳酸脱氢酶活性,减轻I/R引起的脑损伤。从这项研究中出现的一个更重要的发现是,松属素正常化的梗死面积升高I/R。结论:松属素显示了通过抗氧化,抗炎和抗凋亡机制的神经保护作用。(C)2014年波兰科学院药理学研究所。出版社:Elsevier Urban & Partner Sp. z o.o. All rights reserved.
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.