橙皮苷甲基查尔酮抑制α-葡萄糖苷酶的分子机制  

Inhibitory mechanism of hesperidin methyl chalcone againstα-glucosidase

作　　者：白璐 刘本国[1] 张浩 BAI Lu;LIU Benguo;ZHANG Hao(School of Food Science,Henan Institute of Science and Technology,Xinxiang 453003,China;Shaanxi Research Institute of Agricultural Products Processing Technology,Xi′an 710021,China)

机构地区：[1]河南科技学院食品学院,河南新乡453003 [2]陕西农产品加工技术研究院,陕西西安710021

出　　处：《河南工业大学学报(自然科学版)》2025年第1期50-57,125,共9页Journal of Henan University of Technology:Natural Science Edition

基　　金：陕西省重点研发计划项目(2023-YBNY-190)。

摘　　要：α-葡萄糖苷酶是治疗2型糖尿病的重要靶点,寻找天然生物活性成分的α-葡萄糖苷酶抑制剂具有重要意义。橙皮苷甲基查尔酮(Hesperidin methyl chalcone,HMC)具有丰富的生物利用度、代谢稳定性和良好的组织吸收特性,利用酶抑制动力学、荧光猝灭试验、热力学研究和分子对接技术考察HMC的酶抑制和互作机理。HMC和阿卡波糖的IC 50分别为(1.39±0.03)、(1.84±0.02)mg/mL,表明HMC对α-葡萄糖苷酶的抑制效果优于阿卡波糖;疏水作用力是HMC与α-葡萄糖苷酶结合的主导作用力,结合位点数为1;通过分子对接发现,HMC与α-葡萄糖苷酶Glu771、Arg387、Arg428、Asp392、Asp568、Trp391和Phe384的氨基酸残基存在氢键作用;此外,HMC还与酶的众多疏水残基(Trp789、Trp715、Trp391、Phe389、Phe385、Arg428、Phe444、Val440、Glu429、Pro441、Lys439、Phe384、Arg387、Asp568、Tyr709和Glu771)存在疏水作用。α-葡萄糖苷酶与HMC的结合作用越强,越能减少与底物的结合,从而达到降低餐后高血糖的目的。α-Glucosidase is a crucial target for the treatment of type 2 diabetes,and the search for bioactive ofα-glucosidase inhibitors holds significant importance.Hesperidin methyl chalcone(HMC)boasts rich bioavailability,metabolic stability,and favorable tissue absorption properties.In the present investigation,a comprehensive suite of experimental and computational techniques were employed to elucidate the inhibitory impact of HMC onα-glucosidase activity as well as to delineate the underlying molecular interaction mechanism.Specifically,enzyme inhibition kinetics were scrutinized to quantify the potency of HMC-mediatedα-glucosidase inhibition.Furthermore,fluorescence quenching experiments were conducted to probe the binding interactions between HMC and the target enzyme.Complementary thermodynamic studies were also performed to delineate the driving forces governing the HMC-α-glucosidase association.Finally,in silico molecular docking simulations were leveraged to gain atomic-level insights into the binding mode and key intermolecular interactions dictating the HMC-enzyme complex formation.The IC 50 values of HMC and acarbose were(1.39±0.03)mg/mL and(1.84±0.02)mg/mL,respectively,indicating that HMC exhibits superior inhibitory effects onα-glucosidase compared with acarbose.Hydrophobic forces dominated the binding between HMC andα-glucosidase,with a binding site of 1.Synchronous and 3D fluorescence spectra indicated that the interaction between HMC andα-glucosidase resulted in changes in the microenvironment around the tryptophan and tyrosine residues ofα-glucosidase,which affected the conformation of the polypeptide chain of the enzyme.The molecular docking results showed that HMC interacted with the amino acid residues ofα-glucosidase Glu771,Arg387,Arg428,Asp392,Asp568,Trp391,and Phe384 by the hydrogen bond interaction.In addition,HMC exhibited hydrophobic interactions with numerous hydrophobic residues of the enzymes,including Trp789,Trp715,Trp391,Phe389,Phe385,Arg428,Phe444,Val440,Glu429,Pro441,Lys439,

关 键 词：橙皮苷甲基查尔酮 Α-葡萄糖苷酶 热力学 荧光 分子对接 

分 类 号：TS201.2[轻工技术与工程—食品科学]