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胡椒碱可恢复链脲佐菌素诱导的认知障碍:对脑脊液和海马体氧化平衡的见解。

Piperine restores streptozotocin-induced cognitive impairments: Insights into oxidative balance in cerebrospinal fluid and hippocampus.

作者信息

Khalili-Fomeshi Mohsen, Azizi Mohammad Golparvar, Esmaeili Mohammad Reza, Gol Mohammad, Kazemi Sohrab, Ashrafpour Manouchehr, Moghadamnia Ali Akbar, Hosseinzadeh Soheila

机构信息

Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

出版信息

Behav Brain Res. 2018 Jan 30;337:131-138. doi: 10.1016/j.bbr.2017.09.031. Epub 2017 Sep 20.

DOI:10.1016/j.bbr.2017.09.031
PMID:28939403
Abstract

Piperine has been shown to have antioxidant activity and a cognitive-enhancing effect following long-term oral administration. In a comparative study of memantine, the current investigation threw light on the cognitive benefits of piperine. Lipid peroxidation and the ferric reducing antioxidant power (FRAP) of cerebrospinal fluid (CSF) and hippocampus in streptozotocin (STZ)-induced experimental dementia of the Alzheimer's type was measured. After reaching a criterion in a memory test, STZ-induced rats received piperine [2.5, 5, and 10mg/kg, intraperitoneally (i.p.)], vehicle, and memantine (10mg/kg, i.p.) for two weeks after the first STZ administration, or two weeks before and one week after, as a preventive approach. After the behavioral studies, samples were taken for biochemical and histological assays. An appropriate concentration of piperine (2.5mg/kg), on a daily basis, effectively increased the number of correct (non-repeated) arm entries and repressed reentry to a previously visited arm, in terms of reference errors as well as memantine (10mg/kg, i.p.), irrespective of the dose administered. The cognitive-enhancing effect induced by piperine at a relevant dose was simultaneous with CSF and hippocampal malonaldehyde decrement, and the redox balance was established to some extent by maintaining the FRAP levels of CSF near to those of the control. Similarly, the neuroprotective properties of piperine are in accordance with histopathological outcomes, which have shown an increased number of live cresyl violet (CV)-positive neurons in a dentate gyrus (DG) subregion. Therefore, the effects of piperine on the redox balance of CSF and hippocampal neurons may certainly contribute to the cognitive-enhancing activity of the drug.

摘要

胡椒碱经长期口服给药后已显示出抗氧化活性和认知增强作用。在一项与美金刚的对比研究中,当前的调查揭示了胡椒碱的认知益处。对链脲佐菌素(STZ)诱导的阿尔茨海默病型实验性痴呆大鼠的脑脊液(CSF)和海马中的脂质过氧化及铁还原抗氧化能力(FRAP)进行了测量。在记忆测试达到标准后,STZ诱导的大鼠在首次给予STZ后接受胡椒碱[2.5、5和10mg/kg,腹腔注射(i.p.)]、溶剂对照以及美金刚(10mg/kg,i.p.),持续两周,或者作为预防措施,在首次给予STZ前两周和后一周给药。行为学研究结束后,采集样本进行生化和组织学分析。每天给予适当浓度的胡椒碱(2.5mg/kg),在参考误差方面以及与美金刚(10mg/kg,i.p.)一样,有效增加了正确(非重复)进入臂的次数,并抑制了再次进入先前访问过的臂。胡椒碱在相关剂量下诱导的认知增强作用与脑脊液和海马丙二醛的减少同时出现,并且通过将脑脊液的FRAP水平维持在接近对照水平,在一定程度上建立了氧化还原平衡。同样,胡椒碱的神经保护特性与组织病理学结果一致,该结果显示齿状回(DG)亚区域中活的甲酚紫(CV)阳性神经元数量增加。因此,胡椒碱对脑脊液和海马神经元氧化还原平衡的影响肯定有助于该药物的认知增强活性。

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