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岩藻黄质对实验性大鼠脑室注射链脲佐菌素(ICV-STZ)诱导的认知障碍的神经保护作用。

Neuroprotective Effect of Fucoxanthin against Intracerebroventricular Streptozotocin (ICV-STZ) Induced Cognitive Impairment in Experimental Rats.

机构信息

Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India.

Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India.

出版信息

Curr Alzheimer Res. 2021;18(8):623-637. doi: 10.2174/1567205018666211118144602.

Abstract

BACKGROUND

Alzheimer's disease (AD) is a neurological disorder characterized by loss of memory and cognitive functions caused by oxidative stress, neuroinflammation, change in neurotransmitter levels, and excessive deposition of Aβ plaques. Fucoxanthin is a carotenoid with potential antioxidant, anti-inflammatory, and neuroprotective actions.

OBJECTIVE

In the present study, fucoxanthin was employed as a protective strategy in Intracerebroventricular Streptozotocin (ICV-STZ) induced experimental model of cognitive impairment.

METHODS

STZ was injected twice ICV (3 mg/kg) on alternate days 1 and 3, and Wistar rats were evaluated for the memory analysis using Morris water maze and elevated plus-maze. Fucoxanthin at low 50 mg/kg, p.o. and high dose 100 mg/kg, p.o. was administered for 14 days. All animals were sacrificed on day 29, and brain hippocampus tissue after isolation was used for biochemical (MDA, nitrite, GSH, SOD and Catalase), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (ACh, GABA Glutamate), Aβ and Tau protein measurements.

RESULTS

STZ-infused rats showed significant impairment in learning and memory, increased oxidative stress (MDA, nitrite), reduced antioxidant defense (GSH, SOD and Catalase), promoted cytokine release, and change in neurotransmitters level. However, fucoxanthin improved cognitive functions, restored antioxidant levels, reduced inflammatory markers dose-dependently, and restored neurotransmitters concentration.

CONCLUSION

The finding of the current study suggests that fucoxanthin could be the promising compound for improving cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms, and inhibition of acetylcholinesterase (AChE) enzyme activities, Aβ accumulation, and tau protein.

摘要

背景

阿尔茨海默病(AD)是一种神经退行性疾病,其特征是记忆和认知功能丧失,这是由氧化应激、神经炎症、神经递质水平变化以及 Aβ 斑块的过度沉积引起的。岩藻黄质是一种具有潜在抗氧化、抗炎和神经保护作用的类胡萝卜素。

目的

本研究采用岩藻黄质作为一种保护策略,用于脑室注射链脲佐菌素(ICV-STZ)诱导的认知障碍实验模型。

方法

STZ 两次脑室注射(3mg/kg),隔日 1 次和 3 次,用 Morris 水迷宫和高架十字迷宫评估大鼠的记忆分析。岩藻黄质低剂量 50mg/kg,po 和高剂量 100mg/kg,po 给药 14 天。所有动物于第 29 天处死,分离大脑海马组织后用于生化(MDA、亚硝酸盐、GSH、SOD 和 Catalase)、神经炎症(TNF-α、IL-1β 和 IL-6)、神经递质(ACh、GABA 谷氨酸)、Aβ 和 Tau 蛋白的测量。

结果

STZ 注射大鼠学习和记忆能力显著受损,氧化应激增加(MDA、亚硝酸盐),抗氧化防御降低(GSH、SOD 和 Catalase),促炎细胞因子释放,神经递质水平改变。然而,岩藻黄质改善了认知功能,恢复了抗氧化水平,剂量依赖性地降低了炎症标志物,恢复了神经递质浓度。

结论

本研究的结果表明,岩藻黄质通过抗氧化、抗炎和神经保护机制,以及抑制乙酰胆碱酯酶(AChE)酶活性、Aβ 积累和 Tau 蛋白,可能是改善认知功能的有前途的化合物。

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