OBJECTIVE:Alzheimer's disease (AD) is an acquired neurological disorder of cognitive and behavioral impairments, with a long and progressive route. Currently, efforts are being made to develop potent drugs that target multiple pathological mechanisms that drive the successful treatment of AD in human beings. The development of nano-drug delivery systems has recently emerged as an effective strategy to treat AD. METHODS:In the present study, the protective effect of Phytol and Phytol loaded Poly Lactic-co-Glycolic Acid nanoparticles (Phytol-PLGANPs) were evaluated in Wistar rat scopolamine model of AD. RESULTS AND DISCUSSION:The consumption of Phytol and Phytol-PLGANPs significantly ameliorated the cognitive deficits caused by scopolamine on spatial and short term memory. Phytol and Phytol-PLGANPs significantly enhanced the cholinergic effect by inhibiting both acetylcholinesterase and butyrylcholinesterase (AChE & BuChE), β-secretase 1 (BACE1) activity, attenuating macromolecular damage, reducing reactive oxygen species (ROS) and reactive nitrogen species (RNS) level by activating antioxidative defense system (Superoxide dismutase and catalase) and restoring glutathione metabolizing enzyme systems (Glutathione S-transferase) and also regulating the apoptotic mediated cell death. Moreover, in vivo toxicity study suggests that Phytol and Phytol-PLGANPs did not cause any adverse pathological alteration in rats treated with a higher concentration of Phytol-PLGANPs (200 mg/kg). Pharmacokinetic study revealed that Phytol-PLGANPs enhanced the biodistribution and sustained the release profile of phytol in the brain and plasma. CONCLUSION:Overall, the outcome of the study suggests that Phytol and Phytol-PLGANPs act as a potent candidate with better anti-amnesic effects and multi-faceted neuroprotective potential against scopolamine-induced memory dysfunction in Wistar rats.

译文

目的:阿尔茨海默氏病(AD)是一种认知和行为障碍的获得性神经系统疾病,其病程长且进展。当前,正在努力开发针对多种病理机制的有效药物,所述多种病理机制驱动人类成功治疗AD。纳米药物递送系统的开发近来已经成为治疗AD的有效策略。
方法:在本研究中,在Wistar大鼠东碱AD模型中评估了Phytol和Phytol负载的聚乳酸-乙醇酸共聚物纳米颗粒(Phytol-PLGANPs)的保护作用。
结果与讨论:服用植物甾醇和植物甾醇-PLGANPs可以显着减轻东pol碱对空间和短期记忆的认知缺陷。 Phytol和Phytol-PLGANPs通过抑制乙酰胆碱酯酶和丁酰胆碱酯酶(AChE&BuChE),β-分泌酶1(BACE1)活性,减弱大分子破坏,降低活性氧(ROS)和活性氮(RNS)的水平来显着增强胆碱能作用通过激活抗氧化防御系统(超氧化物歧化酶和过氧化氢酶)并恢复谷胱甘肽代谢酶系统(谷胱甘肽S-转移酶),并调节凋亡介导的细胞死亡。此外,体内毒性研究表明,在以较高浓度的Phytol-PLGANPs(200μg/ kg)处理的大鼠中,Phytol和Phytol-PLGANPs不会引起任何不良的病理改变。药代动力学研究表明,Phytol-PLGANPs可以增强植物体内在大脑和血浆中的生物分布并维持其释放特性。
结论:总的来说,研究结果表明,Phytol和Phytol-PLGANPs可以作为强效候选物,具有更好的抗遗忘作用,并且具有多种抗东sco碱诱导的Wistar大鼠记忆功能障碍的神经保护作用。

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