A Novel spice-antioxidant-based nano-vehicle as a putative green alternative of synthetic AChE inhibitor drugs.

IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Izaz Monir Kamal, Anamika Das, Sanjukta Datta, Kaninika Paul, Sasanka Chakrabarti, Saikat Chakrabarti, Paramita Bhattacharjee
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引用次数: 0

Abstract

The present treatment for Alzheimer's disease (AD) involves well known synthetic acetylcholine esterase (AChE) inhibitor drugs which besides having short duration of action also have deleterious impact on human health. Therefore, there is a need for natural plant-based biomolecule(s) with potential AChE inhibition activity (ies). The aim of the work is to design a spice-based nano-vehicle as a novel green alternative of synthetic AD drugs by nanoencapsulating a solvent-less supercritical CO2 extract of small cardamom seeds (SCE) having a synergistic consortium of five antioxidant molecules, using polyethylene glycol and emulsifiers, selected based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analyses. Ellman's assay and enzyme inhibition kinetics of the antioxidant molecules as well as the extract and its nanoliposomal formulation (SCE-NL) were performed, followed by rigorous molecular docking and dynamics studies using MM-PBSA and umbrella sampling. The antioxidants exhibited significant AChE inhibition in vitro, individually with 1, 8-cineole having the least IC50 value of 65.53 ± 0.05 µg/mL. . Although SCE-NL had higher IC50 value (575.67 ± 0.5 µg/mL) vis-à-vis that of rivastigmine (67.52 ± 0.02 µg/mL), it is safer for usage being 'green'.The Lineweaver-Burk plots (Vmax ∼1.04 mM/min) revealed competitive mode(s) of inhibition of AChE with each of these antioxidants. Binding energy analyses suggested very good binding free energies and stable docking/binding complexes (between the antioxidants and AChE). This study has delivered a nanoliposomal vehicle of food antioxidants as a putative 'green' alternative of synthetic AChE inhibitor drugs.Communicated by Ramaswamy H. Sarma.

一种基于香料抗氧化剂的新型纳米载体,可作为合成 AChE 抑制剂药物的绿色替代品。
目前治疗阿尔茨海默病(AD)的药物包括众所周知的合成乙酰胆碱酯酶(AChE)抑制剂,这些药物除了作用时间短之外,还会对人体健康产生有害影响。因此,需要具有潜在乙酰胆碱酯酶抑制活性的天然植物生物分子。这项工作的目的是设计一种基于香料的纳米载体,通过使用聚乙二醇和乳化剂(根据吸收、分布、代谢、排泄和毒性(ADMET)分析选出),将具有五种抗氧化剂分子协同组合的小豆蔻籽(SCE)无溶剂超临界二氧化碳提取物纳米封装,作为合成抗逆转录酶药物的新型绿色替代品。对抗氧化剂分子、提取物及其纳米脂质体制剂(SCE-NL)进行了埃尔曼氏测定和酶抑制动力学研究,然后利用 MM-PBSA 和伞状取样进行了严格的分子对接和动力学研究。抗氧化剂在体外表现出明显的 AChE 抑制作用,其中 1,8-松油的 IC50 值最小,为 65.53 ± 0.05 µg/mL。.尽管 SCE-NL 的 IC50 值(575.67 ± 0.5 µg/mL)比利伐斯的明的 IC50 值(67.52 ± 0.02 µg/mL)高,但由于它是 "绿色 "的,使用起来更安全。结合能分析表明,(抗氧化剂和 AChE 之间的)结合自由能非常高,对接/结合复合物非常稳定。这项研究提供了一种食品抗氧化剂纳米脂质体载体,可作为合成 AChE 抑制剂药物的 "绿色 "替代品。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Biomolecular Structure & Dynamics
Journal of Biomolecular Structure & Dynamics 生物-生化与分子生物学
CiteScore
8.90
自引率
9.10%
发文量
597
审稿时长
2 months
期刊介绍: The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.
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