Antiparasitic Activity and Potential Active Compounds from Azadirachta Indica Revealed by Affinity Ultrafiltration Chromatography–Mass Spectrometry with Acetylcholinesterase and Lactate Dehydrogenases  

作　　者：Minxia Fan Tojofaniry Fabien Rakotondrabe Guilin Chen Mingquan Guo 

机构地区：[1]Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture,Wuhan Botanical Garden,Chinese Academy of Sciences,Sino-Africa Joint Research Center,Chinese Academy of Sciences,Wuhan 430074,China [2]Ningbo Cixi Institute of Biomedical Engineering,Ningbo Institute of Materials Technology and Engineering,Chinese Academyof Sciences,Ningbo315300,China

出　　处：《Journal of Analysis and Testing》2024年第4期403-414,共12页分析检测(英文)

基　　金：the financial support from the Natural Science Foundation of Hubei Province(2021CFB263);the Opening Project of Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients(HLPAI2023003)。

摘　　要：Azadirachta indica(A.indica)has traditionally been used to treat parasitic diseases,while its antiparasitic compounds and their mechanism remain ambiguous.Acetylcholinesterase(AChE)and lactate dehydrogenases(LDH)are the key target enzymes in the survival of parasites.At present,an integrated method combining affinity ultrafiltration-liquid chromatography–mass spectrometry(UF-LC–MS)with molecular docking was established to screen antiparasitic compounds targeting AChE and LDH from A.indica.The alamarBlue^(®)and Ellman method,which revealed that ethyl acetate(EA)fraction exhibited powerful antitrypanosomic and AChE inhibitory activity,was submitted to UF-LC–MS and molecular docking.Afterward,D-(+)-catechin and(-)-epicatechin were considered potential AChE inhibitors with binding degree(BD)values of 38.04–38.43%and binding energy(BE)values from-8.29 to-7.76 kcal/mol.Carnosol was identified as a potential AChE and LDH dual inhibitor with BD values of 42.01%and 26.02%,and BE values of-9.62 and-9.06 kcal/mol,respectively.Finally,carnosol,D-(+)-catechin,and(-)-epicatechin displayed significant AChE inhibitory activity with the IC_(50)values of 40.66±3.10,54.98±9.65,and 72.93±1.32μmol/L,respectively.Collectively,the integrated strategy is effective to screen and identify AChE and LDH inhibitors from A.indica,and D-(+)-catechin,(-)-epicatechin,and carnosol are expected to be natural lead compounds for the treatment of parasitic diseases.Besides using UF-LC–MS to screen for antiparasitic compounds from A.indica,this study offers a strategy for screening active components of medicinal plants.

关 键 词：Azadirachta indica Parasitic diseases UF-LC-MS Molecular docking 

分 类 号：R284.1[医药卫生—中药学] O657.63[医药卫生—中医学]