核苷、烟酰胺腺嘌呤二核苷酸、5′-三磷酸腺苷、肌苷、烟酰胺核苷和烟酰胺单核苷酸对α-淀粉酶和α-葡萄糖苷酶的抑制作用

IF 2.6 3区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Journal of Food Science and Technology-mysore Pub Date : 2020-08-24 DOI:10.25177/JFST.5.4.RA.10644
F. Ghorbani, Masoomeh Ghorbani, Arezou Ghahghaee, Sift Desk Journals Open Access Journals
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引用次数: 1

摘要

糖尿病是一组以长期高血糖为特征的代谢紊乱。抑制碳水化合物水解酶导致葡萄糖吸收减少,被认为是控制糖尿病的有效方法之一。蔬菜、水果、牛奶和鱼类是核苷和肌苷(INO)、烟酰胺核苷(NR)和烟酰胺单核苷酸(NMN)的良好来源,具有多种健康益处。这些化合物对酶的抑制/激活具有良好的结构特征,包括几个可用的氢键受体和供体,灵活的主链和疏水性。α-淀粉酶(α-Amy)和α-葡萄糖苷酶(α-Glu)的底物具有类似核苷的官能团(OH)。因此,本研究旨在评价核苷类化合物对α- amy和α-Glu的抑制作用。α-Glu在腺苷(ADN)、三磷酸腺苷(AMP)、NR、INO、三磷酸腺苷(ATP)、烟酰胺腺嘌呤二核苷酸(NAD)、二磷酸腺苷(ADP)核糖、ADP-葡萄糖和NMN存在时的中位抑制浓度(IC50)值分别为208.6±3.8、254.1±5.2、177.7±4.8、192.1±5.2、215.9±2.7、65.4±1.3、63.4±2.2、75.6±4.2和196.1±2.6。ADN、AMP、NR、INO、ATP、NAD、adp -核糖、adp -葡萄糖和NMN存在时α-Amy的IC50值分别为145.3±2.4、202.3±3.9、127.7±4.8、163.5±3.6、185.3±1.2、80.4±2.8、64.8±4.7、51.1±1.6和166.5±1.4。此外,α-Glu和α-Amy在竞争模式和非竞争模式下的NAD Ki值分别为13.8±0.8和18.6±2.4 μM。此外,NR与α-Glu和α-Amy活性位点的结合能分别为-7.8和-6.8 kcal/mol, INO -7.3和-6.9,ATP -8.3和-7.3,NAD -10.0和-8.5,adp -核糖-8.7和-7.4,adp -葡萄糖-8.9和-7.6,cAMP 6.6和-6.3,NMN -6.8和-7.0 kcal/mol。这些抗氧化抑制剂可能是潜在的抗糖尿病药物,不仅可以降低血糖指数,还可以限制主要活性氧(ROS)产生途径的活性。
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The Inhibitory Effects of Nucleosides, Nicotinamide Adenine Dinucleotide, Adenosine 5'-Triphosphate, Inosine, Nicotinamide Riboside and Nicotinamide Mononucleotide Against α-Amylase and α-Glucosidase Enzymes
Diabetes is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time. Inhibition of carbohydrate hydrolyzing enzymes leads to decrease in the absorption of glucose which is considered as one of the effective managements of diabetes mellitus. Vegetable, fruit, milk and fish are good sources of nucleosides and inosine (INO), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) with versatile health benefits. The welladapted structural features of these compounds for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone and hydrophobic nature. The substrates of α-amylase (α-Amy) and α-Glucosidase (α-Glu), known as key absorbing enzymes, have functional groups (OH groups) resembling nucleosides. Therefore, the present study was conducted to evaluate the inhibitory properties of nucleosides against αAmy and α-Glu. The median inhibition concentration (IC50) values for α-Glu in the presence of adenosine (ADN), adenosine triphosphate (AMP), NR, INO, adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), Adenosine diphosphate (ADP)-ribose, ADP-glucose and NMN were determined 208.6±3.8, 254.1±5.2, 177.7±4.8, 192.1±5.2, 215.9±2.7, 65.4±1.3, 63.4±2.2, 75.6±4.2 and 196.1±2.6, respectively. The IC50 values α-Amy in the presence of ADN, AMP, NR, INO, ATP, NAD, ADP-ribose, ADP-glucose and NMN were determined 145.3±2.4, 202.3±3.9, 127.7±4.8, 163.5±3.6, 185.3±1.2, 80.4±2.8, 64.8±4.7, 51.1±1.6 and 166.5±1.4, respectively. Moreover, the Ki values of NAD were calculated as 13.8±0.8 and 18.6±2.4 μM for α-Glu and α-Amy in a competitive-mode and noncompetitive -mode inhibition. In addition, to communicate with the active site of α-Glu and α-Amy respectively, NR presented a binding energy of -7.8 and -6.8 kcal/mol, INO -7.3 and -6.9, ATP -8.3 and -7.3, NAD -10.0 and -8.5, ADP-ribose -8.7 and -7.4, ADP-glucose -8.9 and -7.6, cAMP 6.6 and -6.3 and NMN -6.8 and -7.0 kcal/mol. These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index, but also to limit the activity of the major reactive oxygen species (ROS) producing pathways.
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
274
审稿时长
11 months
期刊介绍: The Journal of Food Science and Technology (JFST) is the official publication of the Association of Food Scientists and Technologists of India (AFSTI). This monthly publishes peer-reviewed research papers and reviews in all branches of science, technology, packaging and engineering of foods and food products. Special emphasis is given to fundamental and applied research findings that have potential for enhancing product quality, extend shelf life of fresh and processed food products and improve process efficiency. Critical reviews on new perspectives in food handling and processing, innovative and emerging technologies and trends and future research in food products and food industry byproducts are also welcome. The journal also publishes book reviews relevant to all aspects of food science, technology and engineering.
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