Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
Pharmacol Biochem Behav. 2018 Dec;175:33-46. doi: 10.1016/j.pbb.2018.08.007. Epub 2018 Aug 30.
Sporadic Alzheimer's disease (SAD), an age-associated dementia, is described as neuronal loss and marked cognitive impairment. Ellagic acid (EA) is a phenolic phytoconstituent obtained from grains and fruits, having evident antioxidant effects and known to modulate several endogenous molecular signals in humans in a beneficial way. The current study evaluated the safety profile of EA in the SH-SY5Y human neuroblastoma cell line, performing anti-oxidative effect by DPPH assay, and evaluating anti-AchE (acetylcholinesterase) effect against AchE enzyme from Electrophorus electricus. The observations were further confirmed by in vivo therapeutic effects in streptozotocin (STZ)-induced SAD rats in the context of altered biochemical and behavioral features. Treatment with EA (50 mg/kg, p.o.) for 30 days revealed reduction in STZ (3 mg/kg i.c.v.) prompted SAD and associated biochemical abnormalities in experimental rats which included diminished oxidative stress profile, pro-inflammatory markers i.e. GFAP and CRP; AchE level, and amyloid-β plaque level. Moreover, an elevated level of synaptophysin indicated improved synaptic connectivity, and intact neural architecture showed neuroprotection in the EA group. Furthermore, the behavioral investigation by maze paradigms revealed reduced locomotor behavior, irregular spontaneous alternation, declination in memory score and increased memory errors in SAD rats. EA treatment normalized these SAD-associated abnormal behavioral representations in rats. Hence our findings suggest neuroprotective effects of EA and improvement in cognitive behavior in SAD rats.
散发性阿尔茨海默病(SAD)是一种与年龄相关的痴呆症,其特征是神经元丧失和明显的认知障碍。鞣花酸(EA)是一种从谷物和水果中提取的酚类植物成分,具有明显的抗氧化作用,并被证明可以以有益的方式调节人类体内的几种内源性分子信号。本研究评估了 EA 在 SH-SY5Y 人神经母细胞瘤细胞系中的安全性,通过 DPPH 测定法评估其抗氧化作用,并评估对电鳗乙酰胆碱酯酶(AchE)酶的抗 AchE(乙酰胆碱酯酶)作用。通过在改变的生化和行为特征背景下,对链脲佐菌素(STZ)诱导的 SAD 大鼠进行体内治疗效果进一步证实了这些观察结果。用 EA(50mg/kg,po)治疗 30 天可减少 STZ(3mg/kg icv)引起的 SAD 和相关生化异常,包括氧化应激谱降低、促炎标志物 GFAP 和 CRP;AchE 水平和淀粉样蛋白-β斑块水平。此外,突触小体蛋白水平升高表明突触连接得到改善,神经细胞结构完整表明 EA 组具有神经保护作用。此外,通过迷宫范式进行的行为研究表明,SAD 大鼠的运动行为减少,自发交替不规则,记忆评分下降,记忆错误增加。EA 治疗可使 SAD 相关的这些异常行为表现正常化。因此,我们的研究结果表明 EA 具有神经保护作用,并可改善 SAD 大鼠的认知行为。