关键词: (-)-epigallocatechin-3-gallate amyloid β protein gold nanoparticles green synthesis green tea liquid chromatography tandem triple quadrupole mass spectrometry

Mesh : Humans Alzheimer Disease / drug therapy metabolism Amyloid beta-Peptides / antagonists & inhibitors metabolism Catechin / chemistry pharmacology analogs & derivatives Gold / chemistry Ligands Metal Nanoparticles / chemistry therapeutic use Molecular Docking Simulation Peptide Fragments / chemistry antagonists & inhibitors Protein Aggregates / drug effects Camellia sinensis / chemistry

来  源:   DOI:10.2147/IJN.S451070   PDF(Pubmed)

Abstract:
UNASSIGNED: Inhibition of amyloid β protein fragment (Aβ) aggregation is considered to be one of the most effective strategies for the treatment of Alzheimer\'s disease. (-)-Epigallocatechin-3-gallate (EGCG) has been found to be effective in this regard; however, owing to its low bioavailability, nanodelivery is recommended for practical applications. Compared to chemical reduction methods, biosynthesis avoids possible biotoxicity and cumbersome preparation processes.
UNASSIGNED: The interaction between EGCG and Aβ42 was simulated by molecular docking, and green tea-conjugated gold nanoparticles (GT-Au NPs) and EGCG-Au NPs were synthesized using EGCG-enriched green tea and EGCG solutions, respectively. Surface active molecules of the particles were identified and analyzed using various liquid chromatography-tandem triple quadrupole mass spectrometry methods. ThT fluorescence assay, circular dichroism, and TEM were used to investigate the effect of synthesized particles on the inhibition of Aβ42 aggregation.
UNASSIGNED: EGCG as well as apigenin, quercetin, baicalin, and glutathione were identified as capping ligands stabilized on the surface of GT-Au NPs. They more or less inhibited Aβ42 aggregation or promoted fibril disaggregation, with EGCG being the most effective, which bound to Aβ42 through hydrogen bonding, hydrophobic interactions, etc. resulting in 39.86% and 88.50% inhibition of aggregation and disaggregation effects, respectively. EGCG-Au NPs were not as effective as free EGCG, whereas multiple thiols and polyphenols in green tea accelerated and optimized heavy metal detoxification. The synthesized GT-Au NPs conferred the efficacy of diverse ligands to the particles, with inhibition of aggregation and disaggregation effects of 54.69% and 88.75%, respectively, while increasing the yield, enhancing water solubility, and decreasing cost.
UNASSIGNED: Biosynthesis of nanoparticles using green tea is a promising simple and economical drug-carrying approach to confer multiple pharmacophore molecules to Au NPs. This could be used to design new drug candidates to treat Alzheimer\'s disease.
摘要:
抑制淀粉样β蛋白片段(Aβ)聚集被认为是治疗阿尔茨海默氏病的最有效策略之一。(-)-表没食子儿茶素-3-没食子酸酯(EGCG)已被发现在这方面是有效的;然而,由于其生物利用度低,纳米递送被推荐用于实际应用。与化学还原法相比,生物合成避免了可能的生物毒性和繁琐的制备过程。
通过分子对接模拟了EGCG与Aβ42之间的相互作用,使用富含EGCG的绿茶和EGCG溶液合成了绿茶共轭金纳米颗粒(GT-AuNPs)和EGCG-AuNPs,分别。使用各种液相色谱-串联三重四极杆质谱方法鉴定和分析颗粒的表面活性分子。ThT荧光分析,圆二色性,和TEM用于研究合成颗粒对Aβ42聚集的抑制作用。
EGCG以及芹菜素,槲皮素,黄芩苷,谷胱甘肽被鉴定为稳定在GT-AuNP表面的加帽配体。它们或多或少地抑制Aβ42聚集或促进原纤维解聚,EGCG是最有效的,通过氢键与Aβ42结合,疏水相互作用,等。产生39.86%和88.50%的聚集和解聚效应抑制,分别。EGCG-AuNP不如游离EGCG有效,而绿茶中的多种硫醇和多酚加速和优化了重金属解毒。合成的GT-AuNP赋予了颗粒不同配体的功效,抑制聚集和解聚作用分别为54.69%和88.75%,分别,在提高产量的同时,增强水溶性,降低成本。
使用绿茶生物合成纳米颗粒是一种有前途的简单且经济的药物携带方法,可将多种药效基团分子赋予AuNP。这可以用来设计新的候选药物来治疗阿尔茨海默病。
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