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胡椒碱与槲皮素联合可抑制6-羟基多巴胺诱导的实验性大鼠神经退行性变:生化和神经化学证据

Piperine in combination with quercetin halt 6-OHDA induced neurodegeneration in experimental rats: Biochemical and neurochemical evidences.

作者信息

Singh Shamsher, Kumar Puneet

机构信息

Department of Pharmacology, I.S.F College of Pharmacy, Ferozepur Road, Moga, Punjab, India; I.K. Gujral Punjab Technical University, Jalandhar, Punjab, India.

Department of Pharmacology, I.S.F College of Pharmacy, Ferozepur Road, Moga, Punjab, India.

出版信息

Neurosci Res. 2018 Aug;133:38-47. doi: 10.1016/j.neures.2017.10.006. Epub 2017 Oct 19.

DOI:10.1016/j.neures.2017.10.006
PMID:29056550
Abstract

Parkinson's disease (PD) is a multifactorial neurological disorder caused by selective dopaminergic neuronal loss. Quercetin (QC) in combination with piperine (bioenhancer) acts as potential antioxidant, anti-inflammatory and neuroprotective against 6-OHDA rat model of PD. Rats were injected 6-OHDA (8μg/2μl, saline) unilaterally, intranigrally once into right SNpc. Pre-treatment with QC (25 and 50mg/kg, p.o.) alone and combination of QC (25mg/kg, p.o.) with piperine (2.5mg/kg, p.o.) were given for 14days starting from 8th day of 6-OHDA infusion. Post lesions were confirmed by rotational behavior with amphetamine (2.5mg/kg, i.p.) and motor coordination was assessed by narrow beam walk, open field and rotarod apparatus on the weekly basis. On 22nd day, animals were sacrificed and striatum homogenates were used for biochemical (LPO, GSH, Nitrite), neuroinflammatory (TNF-α, IL-1 β and IL-6) and neurotransmitter (dopamine, norepinephrine, serotonin, GABA, glutamate) analysis. Rats pre-treated with QC alone and in combination with piperine have significantly attenuated the 6-OHDA induced rotational behavior and motor deficits. Further, these drugs have significantly improved antioxidant potential, decreased striatal proinflammatory cytokines level as well as restored neurotransmitters level. The neuroprotective enhancement of QC along with piperine is attributed through antioxidant, anti-inflammatory and preventing neurotransmitter alteration mechanisms.

摘要

帕金森病(PD)是一种由选择性多巴胺能神经元丧失引起的多因素神经障碍。槲皮素(QC)与胡椒碱(生物增强剂)联合使用,对帕金森病的6-OHDA大鼠模型具有潜在的抗氧化、抗炎和神经保护作用。大鼠单侧(右侧黑质致密部)脑内注射6-OHDA(8μg/2μl,生理盐水)一次。从6-OHDA注射的第8天开始,单独给予QC(25和50mg/kg,口服)以及QC(25mg/kg,口服)与胡椒碱(2.5mg/kg,口服)联合用药,持续14天。损伤后通过苯丙胺(2.5mg/kg,腹腔注射)诱导的旋转行为来确认,每周通过窄梁行走、旷场和转棒试验评估运动协调性。在第22天,处死动物,取纹状体匀浆进行生化分析(脂质过氧化、谷胱甘肽、亚硝酸盐)、神经炎症分析(肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6)以及神经递质分析(多巴胺、去甲肾上腺素、5-羟色胺、γ-氨基丁酸、谷氨酸)。单独用QC以及QC与胡椒碱联合预处理的大鼠,显著减轻了6-OHDA诱导的旋转行为和运动缺陷。此外,这些药物显著提高了抗氧化能力,降低了纹状体促炎细胞因子水平,并恢复了神经递质水平。QC与胡椒碱的神经保护增强作用归因于抗氧化、抗炎和防止神经递质改变的机制。

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