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Abstract：
Aluminum (Al) is an omnipresent mineral element in the environment. The brain is a central target of Al toxicity, being highly susceptible to oxidative damage. Therefore, recognition of drugs or natural products that guard against Al-mediated neuronal cell death is a powerful strategy for prevention and treatment of neurodegenerative disorders. This work aimed to explore the potential of a leaf extract from Harrisonia abyssinica to modulate the neurobehavioral, biochemical and histopathological activities induced experimentally by Al in vivo. Rats subjected to Al treatment displayed a reduction in learning and memory performance in a passive avoidance test accompanied by a decrease in the hippocampal monoamine and glutamate levels in addition to suppression of Bcl2 expression. Moreover, malondialdehyde (MDA), inflammatory markers (TNF-α, IL-1β), apoptotic markers (caspase-3 and expression of Bax) and extracellular regulated kinase (ERK1/2) levels were elevated along with acetylcholinesterase (AChE) activity, histological changes and marked deposition of amyloid β plaques in the hippocampus region of the brain tissues being observed in Al-treated animals. Concomitant administration of the high dose of H. abyssinica (200 mg/kg b.w.) restored nearly normal levels of all parameters measured, rather than the low dose (100 mg/kg b.w.), an effect that was comparable to the reference drug (rivastigmine). Molecular docking revealed the appropriate potential of the extract components to block the active site of AChE and ERK2. In conclusion, H. abyssinica leaf extract conferred neuroprotection against Al-induced neurotoxic effects, most likely due to its high phenolic and flavonoid content.
摘要：
铝(Al)是环境中普遍存在的矿物元素。大脑是铝毒性的中心目标，极易受到氧化损伤。因此,识别防止Al介导的神经元细胞死亡的药物或天然产物是预防和治疗神经退行性疾病的有力策略。这项工作的目的是探索从哈里夏叶提取物调节神经行为的潜力，Al在体内实验诱导的生化和组织病理学活性。接受Al处理的大鼠在被动回避测试中表现出学习和记忆能力的降低，除了抑制Bcl2表达外，海马单胺和谷氨酸水平也降低。此外，丙二醛（MDA），炎症标志物(TNF-α，IL-1β)，凋亡标志物（caspase-3和Bax的表达）和细胞外调节激酶（ERK1/2）水平与乙酰胆碱酯酶（AChE）活性一起升高，在Al处理的动物中观察到脑组织海马区中淀粉样蛋白β斑块的组织学变化和明显沉积。同时给予高剂量的深渊H.abyssinica（200mg/kgb.w.）恢复了几乎正常水平的所有测量参数，而不是低剂量（100mg/kgb.w.），与参考药物（卡巴拉汀）相当的效果。分子对接揭示了提取物组分阻断AChE和ERK2活性位点的适当潜力。总之,H.苦参素叶提取物赋予神经保护以抵抗铝诱导的神经毒性作用，最有可能是由于其高的酚类和类黄酮含量。
