大麻科毛刺叶胆碱酯酶抑制及抗氧化分子的GC-MS鉴定

Q4 Pharmacology, Toxicology and Pharmaceutics
Onoja O.J., Ugwueze N.J.
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引用次数: 0

摘要

阿尔茨海默病(AD)是一种进行性致命的神经退行性疾病,临床特征为记忆和认知功能障碍。如今,AD影响着全球约3500万人,估计每20年几乎翻一番。据尼日利亚民族医学报道,Cnidoscolus附子(Miller)I.M.Johnston是一种记忆增强剂。缺乏科学证据来证明这些说法的合理性。此外,目前还没有有效的神经治疗剂可用于治疗AD,因此需要寻找新的更有效的药物。本研究旨在评价和鉴定附子叶中具有抗阿尔茨海默病和抗氧化潜力的潜在分子。采用基于按正己烷、乙酸乙酯和甲醇的升序增加洗脱液极性的连续提取程序提取了Cnidoscolus附子(Miller)I.M.Johnston(PCG/UNN/0267)的风干叶。使用标准程序对提取物进行植物化学筛选。乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BuChE)的抑制活性按Ellman法测定。Eserine被用作标准品。使用标准的体外化学分析来评估抗氧化潜力。进行GC-MS(QP2010SE,SHIDMAZU JAPAN)分析,从大多数活性组分中鉴定生物活性化合物。使用单向方差分析进行统计分析,然后在α0.05下进行Dunnett多重比较检验。光化学分析显示存在单宁、树脂、皂苷、类黄酮、酚类、碳水化合物、生物碱和萜类化合物。乙酸乙酯组分在1 mg/mL时表现出最高的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性,IC50值分别为0.288±0.00 mg/mL(82.9%的抑制)和0.440±0.02 mg/mL(75.4%的抑制)。乙酸乙酯部分的金属(亚铁离子)螯合活性也很高,IC50值为0.160±0.00 mg/mL,而EDTA为1 mg/mL(IC50=0.085±0.00 mg/mL)。与1 mg/mL的BHT(IC50=0.074±0.00 mg/mL)相比,乙酸乙酯组分的羟基自由基清除活性更高(IC50=0.352±0.01 mg/mL)。与其他组分相比,乙酸乙酯中的原花青素含量也更高(6.94±0.16 mg花青素/g样品)。对最具活性组分(乙酸乙酯)的GC-MS分析显示总共有56种化合物。所揭示的主要化合物为:正十六烷酸(面积%为13.45%;保留时间为14.863),植物醇(面积%,5.13%;保留时间15.864),十八烷酸(体积%,4.86%;保留时间16.211),9,12,15十八碳三烯酸(Z,Z,Z)(面积%26.85%;保留时间16.09),角鲨烯(%面积2.65%;保留时间20.94)和α-生育酚乙酸酯(%面积1.71%;保留时间23.40)。附子具有抑制参与阿尔茨海默病病理的胆碱酯酶的潜力。鉴定出的分子可能成为治疗阿尔茨海默病的潜在药物先导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
GC-MS Identification of Cholinesterase inhibitory and Antioxidant molecules from leaves of Cnidoscolus aconitifolius (Miller) I.M. Johnston (Euphorbiaceae).
Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disease, clinically characterized by memory and cognitive dysfunction. AD affects about 35 million people worldwide today and is estimated to nearly double every 20 years. Cnidoscolus aconitifolius (Miller) I.M. Johnston has been reported in Nigerian ethnomedicine as a memory enhancer. There is a lack of scientific evidence to justify the claims. Moreover, there are no effective neurotherapeutic agents available for the treatment of AD, hence the need arises for the search of new and more effective agents. This study aims to evaluate and identify potential molecules with anti-Alzheimer’s and antioxidant potentials from Cnidoscolus aconitifolius leaves. The air-dried leaves of Cnidoscolus aconitifolius (Miller) I.M. Johnston (PCG/UNN/0267) were extracted using the successive extraction procedure based on increasing the polarity of the eluent in the ascending order of: n-hexane, ethyl acetate and methanol. Phytochemical screening was carried out on the extracts using standard procedures. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were done according to Ellman’s method. Eserine was used as standard. Antioxidant potentials were evaluated using standard in vitro chemical analyses. A GC-MS (QP2010SE, SHIDMAZU JAPAN) analysis was done to identify bioactive compounds from most active fraction. Statistical analyses were performed using One-way ANOVA followed by Dunnett’s Multiple Comparison test at α0.05. Phytochemical analysis revealed the presence of tannins, resins, saponins, flavonoids, phenols, carbohydrates, alkaloids, and terpenoids. Ethyl acetate fraction demonstrated the highest acetylcholinesterase and butyrylcholinesterase inhibitory activity at 1 mg/mL with IC50 values of 0.288±0.00 mg/mL (82.9% inhibition) and 0.440±0.02 mg/mL ((75.4% inhibition), respectively compared to eserine (IC50=0.050±0.01 mg/mL) for AChE and (IC50=0.049±0.00 mg/mL) for BuChE. Metal (ferrous ion) chelating activity was also high in the ethyl acetate fraction with IC50 value of 0.160±0.00 mg/mL compared to EDTA (IC50 = 0.085±0.00 mg/mL) at 1 mg/mL. Hydroxyl radical scavenging activity was higher in the ethyl acetate fraction (IC50 = 0.352±0.01 mg/mL) when compared to BHT (IC50 = 0.074±0.00 mg/mL) at 1 mg/mL. The pro-anthocyanidin content was also higher in ethyl acetate (6.94±0.16 mg cyanidin/g of sample) compared to other fractions. GC-MS analysis of the most active fraction (ethyl acetate) revealed a total of 56 compounds.The major compounds revealed were: n-Hexadecanoic acid (Area % of 13.45%; Retention time of 14.863), Phytol (Area % of 5.13%; Retention time of 15.864), Octadecanoic acid (Area % of 4.86%; Retention time of 16.211), 9, 12, 15-Octadecatrienoic acid (Z,Z,Z) (Area % of 26.85%; Retention time of 16.09), Squalene (% Area of 2.65%; Retention time of 20.94) and alpha-Tocopheryl acetate (% Area of 1.71%; Retention time of 23.40). C. aconitifolius has the potential to inhibit cholinesterase enzymes involved in the pathology of Alzheimer’s disease. The molecules identified could serve as potential drug leads in the management of Alzheimer’s disease.
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来源期刊
Current Enzyme Inhibition
Current Enzyme Inhibition Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
1.30
自引率
0.00%
发文量
30
期刊介绍: Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
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