Acetyl- and butyrylcholinesterase inhibitory activities of sterols and phlorotannins from Ecklonia stolonifera

As part of this study on the isolation of cholinesterase inhibitors from natural marine products, the bioactivity of the ethanolic extracts from 27 Korean seaweeds were screened using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory assays. Ecklonia stolonifera exhibited promising inhibitory properties against both AChE and BChE. Bioassay-guided fractionation of the active n-hexane and ethyl acetate (EtOAc) soluble fractions, obtained from the ethanolic extract of E. stolonifera, resulted in the isolation of the sterols; fucosterol (1) and 24-hydroperoxy 24-vinylcholesterol (2), from the n-hexane fraction and the phlorotannins; phloroglucinol (3), eckstolonol (4), eckol (5), phlorofucofuroeckol-A (6), dieckol (7), triphlorethol-A (8), 2-phloroeckol (9) and 7-phloroeckol (10), from the EtOAc fraction. Of these, compounds 2, 9 and 10 were isolated from E. stolonifera for the first time. Compounds 4-7, 9 and 10 exhibited inhibitory potential against AChE, with 50% inhibition concentration (IC50) values of 42.66 +/- 8.48, 20.56 +/- 5.61, 4.89 +/- 2.28, 17.11 +/- 3.24, 38.13 +/- 4.95 and 21.11 +/- 4.16 mu M, respectively; whereas, compounds 1, 2, 4 and 6 were found to be active against BChE, with IC50 values of 421.72 +/- 1.43, 176.46 +/- 2.51, 230.27 +/- 3.52 and 136.71 +/- 3.33 mu M, respectively. It has been suggested that the inhibition of these enzymes by the sterols and phlorotannins derived from marine brown algae could be a useful approach for the treatment of Alzheimer's disease.