Unit of Pharmacology, School of Pharmacy, KPJ Healthcare University College, Kota Seriemas, Nilai, Negeri Sembilan, 71800, Malaysia.
Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy, Telangana, 502294, India.
Biomed Pharmacother. 2019 Jan;109:1454-1461. doi: 10.1016/j.biopha.2018.10.189. Epub 2018 Nov 13.
The progressive accumulation of amyloid beta (Aβ) peptide is neurotoxic and leads to Alzheimer's type dementia. Accumulation of Aβ has been associated with dysfunction of hypothalamic-pituitary-adrenal (HPA) axis and elevated pro-inflammatory cytokines. In this study, we investigated the effect of 1δ-1-acetoxyeugenol acetate (DAEA), isolated from Alpinia galanga (L.), on Aβ 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. Aβ was injected by intracerebroventricular (i.c.v.) injection on the 15th day of 28 days. Open field, water maze and step-down 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-α (TNF-α), 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-α 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.
淀粉样β肽（Aβ）的逐渐积累具有神经毒性，并导致阿尔茨海默病类型的痴呆。Aβ的积累与下丘脑-垂体-肾上腺（HPA）轴的功能障碍和促炎细胞因子的升高有关。在这项研究中，我们研究了从 Alpinia galanga（L.）中分离出的 1δ-1-乙酰氧基丁香酚乙酸酯（DAEA）对小鼠 Aβ诱导的神经退行性变的影响。将小鼠用三种不同剂量的 DAEA（12.5mg/kg、25mg/kg 和 50mg/kg）治疗 28 天。在 28 天的第 15 天通过脑室内（i.c.v.）注射 Aβ。在第 27 天进行旷场、水迷宫和步下抑制试验，以分别确定习惯记忆、空间学习以及短期和长期记忆。在行为测试后评估脑匀浆中的乙酰胆碱酯酶（AChE）、皮质酮、生物胺（血清素和多巴胺）、肿瘤坏死因子-α（TNF-α）和抗氧化参数（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），以确定通过神经-免疫-内分泌调节改善认知。25mg/kg 和 50mg/kg 的 DAEA 治疗导致习惯记忆和步下抑制回避任务的显著改善（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 的显著降低（p<0.001）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），生物胺升高，抗氧化标志物增加，这表明 DAEA 对神经保护有潜在影响。我们的研究表明，药物 DAEA 可减轻 HPA 轴介导的应激，并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。
