天然胰脂肪酶抑制剂的虚拟筛选及活性验证  

Virtual Screening and Activity Validation of Natural Pancreatic Lipase Inhibitors

作　　者：郑啸丹 王闪 樊筱園 荆慧娟 阚绮蕃 王洪新[1] 娄在祥[1] ZHENG Xiaodan;WANG Shan;FAN Xiaoyuan;JING Huijuan;KAN Qifan;WANG Hongxin;LOU Zaixiang(School of Food Science and Technology,Jiangnan University,Wuxi 214122,China)

机构地区：[1]江南大学食品学院,江苏无锡214122

出　　处：《食品与生物技术学报》2024年第8期160-172,共13页Journal of Food Science and Biotechnology

基　　金：国家“十四五”重点研发计划项目(2022YFD2101104)。

摘　　要：为了快速筛选安全有效的天然胰脂肪酶(pancreatic lipase,PL)抑制剂,作者采用分子对接、分光光度法、正交t值法及荧光猝灭试验等技术,通过研究胰脂肪酶的构象、活性、动力学和热力学来探究酶与抑制剂之间的相互作用。结果表明,在筛选出的31种化合物中有28种对PL的抑制率超过了50%,其中11种半数抑制质量浓度(the half maximal inhibitory concentration,IC50)低于100μg/mL,特别是(-)-表没食子儿茶素没食子酸酯(EGCG)和辅酶Q9(coenzyme Q9,CoQ9),其半数抑制质量浓度低于奥利司他。作者设计的复合配方包括了木犀草素、杨梅素、槲皮素、异槲皮苷和柚皮苷,当质量浓度为0.5 mg/mL,且各组分的体积比为7∶15∶6∶17∶5时,其抑制率达到了(98.79±2.46)%,效果优于单一组分。配方中的5种物质通过自发键合静态猝灭PL的固有荧光,与PL之间存在疏水相互作用、氢键、离子键及π-π堆积等非共价相互作用。该研究为胰脂肪酶抑制剂提供了多种候选物质。To rapidly identify safe and effective natural inhibitor of pancreatic lipase(PL),the author utilized molecular docking,spectrophotometry,the orthogonal t-value method,and fluorescence quenching experiments to investigate the interaction between PL and the inhibitors by analyzing PL's conformation,activity,kinetics,and thermodynamics.Results showed that of the 31 screened compounds,28 exhibited more than 50%inhibition of PL activity,with 11 compounds demonstrating half-maximal inhibitory concentrations(IC50)below 100μg/mL.Notably,(-)-epigallocatechin gallate(EGCG)and coenzyme Q9(CoQ9)displayed IC50 values lower than that of orlistat.The author designed compound formula,comprising luteolin,myricetin,quercetin,isoquercetin,and naringin,achieved an inhibition rate of(98.79±2.46)%at a concentration of 0.5 mg/mL and a volume ratio of 15∶6∶17∶5,surpassing the efficacy of individual components.The five substances in the formulation spontaneously bind to PL,leading to the quenching of its intrinsic fluorescence through static quenching.Non-covalent interactions,including hydrophobic interactions,hydrogen bonds,ionic bonds,andπ-πstacking,are observed between these substances and PL.This study provides multiple promising candidates for PL inhibitors.

关 键 词：胰脂肪酶 天然产物 分子对接 复方设计 荧光猝灭效应 

分 类 号：TS201.2[轻工技术与工程—食品科学]