文献类型：期刊文献

英文题名：Inhibition mechanisms of four ellagitannins from terminalia chebula fruits on acetylcholinesterase by inhibition kinetics, spectroscopy and molecular docking analyses

作者：Li, Yan-Jun[1];Liang, Cai-Cai[1];Jin, Ling[2];Chen, Juan[1]

第一作者：Li, Yan-Jun

通信作者：Chen, J[1];Jin, L[2]

机构：[1]Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China

第一机构：Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China.|[1073501e14fb35863569f]甘肃中医药大学药学院（西北中藏药协同创新中心办公室）;[10735]甘肃中医药大学;

年份：2023

卷号：302

外文期刊名：SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

收录：;EI(收录号：20232914417485);Scopus(收录号：2-s2.0-85164981853);WOS:【SCI-EXPANDED(收录号:WOS:001060916900001)】；

基金：This work was supported by the Special Foundation for National Science and Technology Basic Resources of China [2018FY100701] ; the Key Program of Natural Science Foundation of Gansu Province, China [20JR10RA584] ; the 2021 project of Gansu Medical Products Administration [2021GSMPA008] ; the 2022 project of State Drug Administration-Key Laboratory of Quality Control of Chinese Medicinal Materials and Decoction Pieces, China [2022GSMPA-KL04] .

语种：英文

外文关键词：Ellagitannins; Acetylcholinesterase; Inhibition mechanism

摘要：Acetylcholinesterase (AChE) is an important therapeutic target for the treatment of Alzheimer's disease (AD), and the development of natural AChE inhibitors as candidates has played a significant role in drug discovery. In this study, the inhibition mechanisms of four ellagitannins, punicalagin, chebulinic acid, geraniin and corilagin, from Terminalia chebula fruits on AChE were investigated systematically by a combination of inhibition kinetics, multi-spectroscopic methods and molecular docking. The kinetic results showed that punicalagin, chebulinic acid and geraniin exhibited strong reversible inhibitory effects on AChE in an uncompetitive manner with the IC50 values of 0.43, 0.50, and 0.51 mM, respectively, while corilagin inhibited AChE activity in a mixed type with the IC50 value of 0.72 mM. The results of fluorescence and UV-vis spectra and fluorescence resonance energy transfer (FRET) revealed that four ellagitannins could significantly quenched the intrinsic fluorescence of AChE though a static quenching along with non-radiative energy transfer. Thermodynamic analyses showed that values of & UDelta;G, & UDelta;H and & UDelta;S were negative, indicating that all binding processes were spontaneous, and the hydrogen bonding and Van der Waals forces might make a great contribution to the formation of inhibitor-AChE complexes. The synchronous fluorescence, three-dimensional (3D) fluorescence, UV-vis, and FT-IR spectra studies suggested that four ellagitannins could lead to alterations in the micro-environment and secondary structure of AChE, and thus the conformational change of AChE. Moreover, molecular docking demonstrated that four ellagitannins could interacted with main amino acid residues of AChE with affinity energies ranging from -9.9 to -8.7 kJ/mol, and further confirmed the above experimental results. This study provided valuable findings for the potential application of four ellagitannins as promising candidates in the exploration of natural AChE inhibitors for the treatment of AD.