Abstract

This study emphasized on the neuroprotective properties of bitter leaf alkaloid-rich extract (BLAE) using transgenic fruit fly (Drosophila melanogaster [D. melanogaster]) model and scopolamine-induced amnesia rats. In vitro antioxidant properties and modulatory effects on key neuronal enzymes were carried out. Thereafter, fruit flies expressing human amyloid precursor protein (hAPP) and BACE-1 genes were treated with BLAE for 7 d to determine survival rate, BACE-1, acetylthiocholine (AChE), glutathione-S-transferase (GST), and catalase activities. Also, the aftermath of the BLAE on the neuronal activities of AChE, butyrylcholine (BChE), monoamine oxidase (MAO), angiotensin-I converting enzyme (ACE), ATP diphosphohydrolase (ATPdase), and ADPdase, catalase, superoxide dismutase (SOD), plus TBARS, and nitric oxide (NO) content in rats treated with scopolamine (1 mg/kg. bwt. i.p.) was evaluated. In addition, the alkaloid characterization for constituent BLAE was determined. The outcomes proved that BLAE displayed antioxidant properties and inhibit activities of AChE, BChE, MAO, ACE, ATPdase, and ADPdase in vitro. Furthermore, transgenic flies treated with the BLAE exhibited significant levels of amelioration on survival rate and activities of BACE-1, AChE, GST, and catalase. In scopolamine-treated rats, AChE, BChE, MAO and NTPdases activities, and antioxidant status were upturned in rats pretreated with BLAE. This study disclosed the neuroprotective property of BLAE, which could be related to its alkaloid constituent, thereby making it a good candidate to explore as curative nutraceutical agent for cognitive impairments and affiliated diseases such as AD.

摘要

本研究使用转基因果蝇 ( Drosophila melanogaster [ D. melanogaster ]) 模型和东莨菪碱诱导的失忆大鼠，重点研究了富含苦叶生物碱的提取物 (BLAE) 的神经保护特性。进行了体外抗氧化特性和对关键神经元酶的调节作用。此后，果蝇表达人类淀粉样前体蛋白 ( hAPP ) 和BACE-1用 BLAE 处理基因 7 天以确定存活率、BACE-1、乙酰硫代胆碱 (AChE)、谷胱甘肽-S-转移酶 (GST) 和过氧化氢酶活性。此外，BLAE 对 AChE、丁酰胆碱 (BChE)、单胺氧化酶 (MAO)、血管紧张素-I 转换酶 (ACE)、ATP 二磷酸水解酶 (ATPdase) 和 ADPdase、过氧化氢酶、超氧化物歧化酶 (SOD) 的神经元活动的影响，加上 TBARS，以及用东莨菪碱 (1  mg/kg. bwt. ip )治疗的大鼠的一氧化氮 (NO) 含量进行了评估。此外，确定了成分 BLAE 的生物碱表征。结果证明 BLAE在体外显示出抗氧化特性并抑制 AChE、BChE、MAO、ACE、ATPdase 和 ADPdase 的活性. 此外，用 BLAE 处理的转基因果蝇对 BACE-1、AChE、GST 和过氧化氢酶的存活率和活性有显着改善。在东莨菪碱处理的大鼠中，在用 BLAE 预处理的大鼠中，AChE、BChE、MAO 和 NTPdases 活性以及抗氧化状态升高。该研究揭示了 BLAE 的神经保护特性，这可能与其生物碱成分有关，因此使其成为探索认知障碍和 AD 等相关疾病的治疗性营养药物的良好候选者。