Neuroprotective effects of 1′δ-1′-acetoxyeugenol acetate on Aβ(25-35) induced cognitive dysfunction in mice
Neuroprotective effects of 1′δ-1′-acetoxyeugenol acetate on Aβ(25-35) induced cognitive dysfunction in mice
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DOI：
10.1016/j.biopha.2018.10.189
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发表时间：
2019-01-01
影响因子：
7.5
通讯作者：
Yellu, Narsimha Reddy
中科院分区：
文献类型：
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作者：
Chellammal, Hanish Singh Jayasingh;Alagarsamy, Veerachamy;Yellu, Narsimha Reddy
淀粉样蛋白β（A β）肽的进行性积累具有神经毒性并导致阿尔茨海默型痴呆。A β的蓄积与下丘脑-垂体-肾上腺（HPA）轴功能障碍和促炎细胞因子升高相关。在这项研究中，我们研究了从大高良姜中分离的1 'δ-1'-乙酰氧基丁香酚乙酸酯（DAEA），对A β（（25-35））诱导的小鼠神经变性的影响。用三种不同剂量的DAEA（12.5mg/kg、25 mg/kg和50 mg/kg）处理小鼠28天。A β（（25-35））侧脑室注射（i. c. v.）在28天的第15天注射。第27天分别进行旷场实验、水迷宫实验和跳台抑制实验，测定大鼠的习惯性记忆、空间学习能力、短时记忆和长时记忆。乙酰胆碱酯酶（AChE），皮质酮，生物胺（5-羟色胺和多巴胺），肿瘤坏死因子-α（TNF-α），和抗氧化剂参数，如超氧化物歧化酶，过氧化氢酶，谷胱甘肽过氧化物酶和维生素C进行了评价后，在脑匀浆中的行为测试，以确定通过神经免疫内分泌调节的认知改善。DAEA 25 mg/kg和50 mg/kg处理后，大鼠的习惯性记忆和抑制性回避任务均得到显著改善（p < 0.001）。在空间学习中，通过减少逃避潜伏期，认知改善显著提高（p < 0.001）。在生化研究中，AChE的显著（p < 0.001）降低表明了卓越的神经保护作用。皮质酮和TNF-α显著降低（p < 0.01），生物胺增加，抗氧化标记物，这表明DAEA对神经保护的潜在影响。我们的研究表明，药物DAEA通过HPA轴减轻应激，调节神经内分泌和神经免疫功能，以改善认知。DAEA可能是治疗神经退行性变的潜在候选药物。
The progressive accumulation of amyloid beta (A beta) peptide is neurotoxic and leads to Alzheimer's type dementia. Accumulation of A beta has been associated with dysfunction of hypothalamic-pituitary-adrenal (HPA) axis and elevated pro-inflammatory cytokines. In this study, we investigated the effect of 1'delta-1'-acetoxyeugenol acetate (DAEA), isolated from Alpinia galanga (L.), on A beta((25-35)) induced neurodegeneration in mice. Mice were treated with three different doses of DAEA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) for 28 days. A beta((25-35) )was injected by intracerebroventricular (i.c.v.) injection on the 15th day of 28 days. Open field, water maze and stepdown inhibitory tests were performed on the 27th day to determine the habituation memory, spatial learning, and short- and long-term memory, respectively. Acetylcholinesterase (AChE), Corticosterone, biogenic amines (serotonin and dopamine), tumour necrosis factor-alpha (TNF-alpha), and antioxidant parameters such as superoxide dismutase, catalase, glutathione peroxidase and vitamin C were evaluated in brain homogenates after behavioural tests to ascertain the cognitive improvement through neuro-immune-endocrine modulation. The DAEA treatment with 25 mg/kg and 50 mg/kg resulted in significant (p < 0.001) improvement of habituation memory and step-down inhibitory avoidance task. In spatial learning, the cognitive improvement was significantly improved (p < 0.001) by reduction in escape latency. In the biochemical study, the significant (p < 0.001) reduction of AChE indicates the preeminent neuroprotection. Corticosterone and TNF-alpha were significantly (p < 0.01) reduced and biogenic amines were increased with antioxidant markers, which signify the potential influence of DAEA on neuroprotection. Our investigation revealed that the drug DAEA attenuates stress mediated through the HPA axis and regulates the neuroendocrine and neuroimmune function to improve the cognition. DAEA could be a potential lead candidate for the treatment of neurodegeneration.