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白皮冬瓜通过抑制 Keap1/Nrf2 轴减轻淀粉样蛋白病理:强调阿尔茨海默病模型中涉及的氧化和炎症应激。

Benincasa hispida alleviates amyloid pathology by inhibition of Keap1/Nrf2-axis: Emphasis on oxidative and inflammatory stress involved in Alzheimer's disease model.

机构信息

A. U. College of Pharmaceutical Sciences, Andhra University Visakhapatnam, 530003, India.

A. U. College of Pharmaceutical Sciences, Andhra University Visakhapatnam, 530003, India.

出版信息

Neuropeptides. 2021 Aug;88:102151. doi: 10.1016/j.npep.2021.102151. Epub 2021 Apr 22.

DOI:10.1016/j.npep.2021.102151
PMID:33932860
Abstract

OBJECTIVES

Alzheimer's disease is a progressive neurodegenerative disorder with cognitive and memory impairment. Benincasa hispida is being used in the treatment of various neurological diseases in Ayurveda system of medicine. The objective of the study was to investigate the effect of Benincasa hispida fruit extract in the Alzheimer's disease rats.

METHODS

Benincasa hispida fruits extract was administered orally for 16 weeks at doses of 250 and 500-mg/kg/day. The cognitive deficits were examined by behavioural tests like Morris water maze test, Y-maze and rota-rod test. Biochemical and neurochemical analysis of Acetylcholine, dopamine, serotonin levels and anti-oxidant, anti-inflammatory markers were evaluated and the mRNA expression of Keap/Nrf2 axis was analysed by RT-PCR.

RESULTS

Aluminum chloride (AlCl) induction altered the behavioural profile and produced significant alterations in the cortical and hippocampal regions of the brain and the treatment with Benincasa hispida extract at doses of 250-mg/kg/day (p<0.05) and 500mg/kg/day (p<0.05) alleviated the acetylcholine, dopamine and serotonin neurotransmitter levels. The antioxidant enzyme markers such as superoxide dismutase (SOD), Catalase (CAT), glutathione (GSH) were increased and the oxidative stress marker malondialdehyde(MDA) was decreased. The inflammatory cytokine levels of TNF-α, IL-1β were decreased in Alzheimer's disease induced rats. We further estimated Keap/Nrf2/HO-1 genes these anti-oxidant genes were upregulated(p < 0.001) in treatment groups. Further, the neuroprotective activity of Benincasa was further confirmed by histopathological studies of hippocampal CA3 fields.

CONCLUSIONS

The findings of the current study indicates Benincasa hispida as a possible neuroprotective alternative for Alzheimer's disease.

摘要

目的

阿尔茨海默病是一种进行性神经退行性疾病,伴有认知和记忆障碍。在印度阿育吠陀医学体系中,冬瓜被用于治疗各种神经疾病。本研究的目的是研究冬瓜果实提取物对阿尔茨海默病大鼠的作用。

方法

冬瓜果实提取物以 250 和 500mg/kg/天的剂量口服给药 16 周。通过行为测试,如 Morris 水迷宫测试、Y 迷宫和转棒测试来检查认知缺陷。评估乙酰胆碱、多巴胺、血清素水平的生化和神经化学分析以及抗氧化、抗炎标志物,并通过 RT-PCR 分析 Keap/Nrf2 轴的 mRNA 表达。

结果

氯化铝(AlCl)诱导改变了行为特征,并对大脑皮质和海马区产生了显著影响,而 250mg/kg/天(p<0.05)和 500mg/kg/天(p<0.05)的冬瓜提取物治疗减轻了乙酰胆碱、多巴胺和血清素神经递质水平。抗氧化酶标志物,如超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)增加,氧化应激标志物丙二醛(MDA)减少。阿尔茨海默病诱导大鼠的炎性细胞因子 TNF-α、IL-1β 水平降低。我们进一步评估了 Keap/Nrf2/HO-1 基因,这些抗氧化基因在治疗组中上调(p<0.001)。此外,通过对海马 CA3 区的组织病理学研究进一步证实了冬瓜的神经保护活性。

结论

本研究的结果表明冬瓜可能是阿尔茨海默病的一种神经保护替代物。

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