Traditional Chinese medicines (TCMs) are one of the most important sources of numerous lead compounds in drug discovery. However, rapid screening and identification of bioactive compounds from complex medicinal plants remain a technical challenge. In this work, a method based on ultrafiltration (UF) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS/MS) was developed to rapidly screen and identify specific acetylcholinesterase (AChE) inhibitors from Terminalia chebula fruits. The water extract of T. chebula fruits was subjected to column chromatography on D101 macroporous resin with increasing proportions of ethanol as the eluent to produce five fractions. Fraction E2 (30% ethanol eluent) exhibited the strongest AChE inhibitory activity and was incubated with AChE. After incubation, ultrafiltration and dissociation, 17 compounds including eight gallotannins, seven ellagitannins and two other compounds in fraction E2 were screened out and their molecular structures were identified by MS/MS spectra. Subsequently, the commercially available standards of chebulagic acid, corilagin,...

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