基于计算机模拟对接以及对2型糖尿病临床靶点的ADMET研究，这些研究与芦丁、咖啡酸、对香豆酸和香草醛对胰腺α-淀粉酶和α-葡萄糖苷酶的体外抑制作用相关。
In silico docking and ADMET studies on clinical targets for type 2 diabetes correlated to in vitro inhibition of pancreatic alpha-amylase and alpha-glucosidase by rutin, caffeic acid, p-coumaric acid, and vanillin.
作者信息
McMillan Jamie, Bester Megan Jean, Apostolides Zeno
机构信息
Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Private Bag X20, Hatfield, Pretoria, 0028 South Africa.
Department of Anatomy, University of Pretoria, Pretoria, South Africa.
出版信息
In Silico Pharmacol. 2025 Mar 14;13(1):42. doi: 10.1007/s40203-025-00324-6. eCollection 2025.
UNLABELLED
Inhibition of pancreatic alpha-amylase and alpha-glucosidase is a common strategy to manage type 2 diabetes. This study focuses on the ability of compounds present in commercially available herbs and spices to inhibit pancreatic alpha-amylase and alpha-glucosidase. In silico molecular docking was performed to evaluate the binding affinity of the compounds present in herbs and spices. Molecular dynamics was performed with acarbose and rutin which had the best docking scores for pancreatic alpha-amylase and alpha-glucosidase. Six compounds (rutin, caffeic acid, p-coumaric acid, vanillin, ethyl gallate, and oxalic acid) with a range of docking scores were subjected to in vitro enzyme kinetic studies using pancreatic alpha-amylase and alpha-glucosidase biochemical assays. Acarbose, a prescribed alpha-amylase and alpha-glucosidase inhibitor, was used as a positive control. Ligands that interacted strongly with the amino acids at a particular site, were conformationally stable and had good docking scores. There was a correlation between the in silico and in vitro binding affinity. Caffeic acid, vanillin, ethyl gallate, and p-coumaric acid had inhibition constant (K) values that were not significantly different ( > 0.05) from the K of acarbose for pancreatic alpha-amylase. Rutin, caffeic acid, vanillin, and p-coumaric acid had K values that were not significantly different ( ˃ 0.05) from the K of acarbose for alpha-glucosidase. The cell viability of these compounds was assessed with the sulforhodamine B (SRB) assay in Caco2 cells. Caffeic acid, p-coumaric acid, rutin, and vanillin had Caco2 IC values that were not significantly different ( ˃ 0.05) from that of acarbose. The evaluated compounds present in herbs and spices can potentially reduce hyperglycemia associated with type 2 diabetes. Herbs and spices with high levels of these compounds were identified and these were common verbena, sweet basil, tarragon, pepper, parsley, sorrel, and vanilla. These herbs and spices may reduce the required dose of prescription drugs, such as acarbose, thereby reducing costs and drug-associated side effects.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40203-025-00324-6.
未标记
抑制胰腺α-淀粉酶和α-葡萄糖苷酶是治疗2型糖尿病的常用策略。本研究聚焦于市售草药和香料中所含化合物抑制胰腺α-淀粉酶和α-葡萄糖苷酶的能力。进行了计算机模拟分子对接以评估草药和香料中化合物的结合亲和力。使用对胰腺α-淀粉酶和α-葡萄糖苷酶对接分数最高的阿卡波糖和芦丁进行分子动力学研究。对六种具有一系列对接分数的化合物（芦丁、咖啡酸、对香豆酸、香草醛、没食子酸乙酯和草酸），采用胰腺α-淀粉酶和α-葡萄糖苷酶生化测定法进行体外酶动力学研究。阿卡波糖，一种已获批的α-淀粉酶和α-葡萄糖苷酶抑制剂，用作阳性对照。与特定位点氨基酸强烈相互作用、构象稳定且对接分数良好的配体。计算机模拟和体外结合亲和力之间存在相关性。咖啡酸、香草醛、没食子酸乙酯和对香豆酸对胰腺α-淀粉酶的抑制常数（K）值与阿卡波糖的K值无显著差异（>0.05）。芦丁、咖啡酸、香草醛和对香豆酸对α-葡萄糖苷酶的K值与阿卡波糖的K值无显著差异（˃0.05）。使用磺基罗丹明B（SRB）测定法评估这些化合物在Caco2细胞中的细胞活力。咖啡酸、对香豆酸、芦丁和香草醛的Caco2 IC值与阿卡波糖的无显著差异（˃0.05）。评估的草药和香料中所含化合物可能会降低与2型糖尿病相关的高血糖。鉴定出含有高水平这些化合物的草药和香料，它们是普通马鞭草、甜罗勒、龙蒿、胡椒、欧芹、酢浆草和香草。这些草药和香料可能会减少阿卡波糖等处方药的所需剂量，从而降低成本和药物相关副作用。
补充信息
在线版本包含可在10.1007/s40203-025-00324-6获取的补充材料。
Zotero 插件