Singh Shamsher, Kumar Puneet
Department of Pharmacology, I.S.F. College of Pharmacy, Ferozepur Road, Ghal Kalan, Moga, India.
Pharmacology. 2016;97(3-4):151-60. doi: 10.1159/000443896. Epub 2016 Jan 30.
Quinolinic acid (QA) is an excitotoxin that induces Huntington's-like symptoms in animals and humans. Curcumin (CMN) is a well-known antioxidant but the major problem is its bioavailability. Therefore, the present study was designed to investigate the effect of CMN in the presence of piperine against QA-induced excitotoxic cell death in rats.
QA was administered intrastriatally at a dose of 200 nmol/2 µl saline, bilaterally. CMN (25 and 50 mg/kg/day, p.o.) and combination of CMN (25 mg/kg/day, p.o.) and with piperine (2.5 mg/kg/day, p.o.) was administered daily for the next 21 days. Body weight and behavioral parameters were observed on 1st, 7th, 14th and 21st day. On the 22nd day, animals were sacrificed and striatum was isolated for biochemical (LPO, nitrite and GSH), neuroinflammatory (interleukin (IL)-1β, IL-6 and TNF-α) and neurochemical (dopamine, norepinephrine, GABA, glutamate, 5-HT, 3,4-dihydroxyphenylacetic acid and homovanillic acid) estimation.
CMN treatment showed beneficial effect against QA-induced motor deficit, biochemical and neurochemical abnormalities in rats. Combination of piperine (2.5 mg/kg/day, p.o.) with CMN (25 mg/kg/day, p.o.) significantly enhanced its protective effect as compared to treatment with CMN alone.
This study has revealed that the combination of CMN and piperine showed strong antioxidant and protective effect against QA-induced behavioral and neurological alteration in rats.
喹啉酸(QA)是一种兴奋性毒素,可在动物和人类中诱发类似亨廷顿氏病的症状。姜黄素(CMN)是一种著名的抗氧化剂,但其主要问题是生物利用度。因此,本研究旨在探讨胡椒碱存在下CMN对QA诱导的大鼠兴奋性毒性细胞死亡的影响。
QA以200 nmol/2 μl生理盐水的剂量双侧脑内注射。在接下来的21天里,每天口服给予CMN(25和50 mg/kg/天)以及CMN(25 mg/kg/天,口服)与胡椒碱(2.5 mg/kg/天,口服)的组合。在第1、7、14和21天观察体重和行为参数。在第22天,处死动物并分离纹状体用于生化指标(脂质过氧化、亚硝酸盐和谷胱甘肽)、神经炎症指标(白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α)以及神经化学指标(多巴胺、去甲肾上腺素、γ-氨基丁酸、谷氨酸、5-羟色胺、3,4-二羟基苯乙酸和高香草酸)的测定。
CMN治疗对QA诱导的大鼠运动功能障碍、生化和神经化学异常具有有益作用。与单独使用CMN治疗相比,胡椒碱(2.5 mg/kg/天,口服)与CMN(25 mg/kg/天,口服)的组合显著增强了其保护作用。
本研究表明,CMN和胡椒碱的组合对QA诱导的大鼠行为和神经改变具有强大的抗氧化和保护作用。