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

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Benincasa hispida alleviates amyloid pathology by inhibition of Keap1/Nrf2-axis: Emphasis on oxidative and inflammatory stress involved in Alzheimer's disease model
Neuropeptides ( IF 2.9 ) Pub Date : 2021-04-22 , DOI: 10.1016/j.npep.2021.102151
Deepthi Rapaka ₁ , Veera Raghavulu Bitra ₁ , Ravishankar Ummidi ₂ , Annapurna Akula ₁

Affiliation

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 (AlCl₃) 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.

中文翻译：

Benincasa hispida 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

目标

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。Benincasa hispida被用于治疗阿育吠陀医学系统中的各种神经系统疾病。该研究的目的是研究Benincasa hispida果实提取物对阿尔茨海默病大鼠的影响。

方法

Benincasa hispida果实提取物以 250 和 500 毫克/公斤/天的剂量口服给药 16 周。通过行为测试如莫里斯水迷宫测试、Y-迷宫和旋转棒测试来检查认知缺陷。评估了乙酰胆碱、多巴胺、血清素水平和抗氧化、抗炎标志物的生化和神经化学分析，并通过 RT-PCR 分析了 Keap/Nrf2 轴的 mRNA 表达。

结果

氯化铝 (AlCl ₃ ) 诱导改变了行为特征，并在大脑的皮质和海马区域产生了显着的改变，并且以 250 毫克/千克/天 ( p <0.05) 和 500毫克/千克的剂量使用硬毛茛提取物进行治疗/天 (p<0.05) 减轻乙酰胆碱、多巴胺和血清素神经递质水平。超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽（GSH）等抗氧化酶标志物升高，氧化应激标志物丙二醛（MDA）降低。在阿尔茨海默病诱导的大鼠中，TNF-α、IL-1β 的炎性细胞因子水平降低。我们进一步估计 Keap/Nrf2/HO-1 基因这些抗氧化基因上调（p < 0.001) 在治疗组中。此外，海马 CA3 区域的组织病理学研究进一步证实了Benincasa的神经保护活性。