IN-VITRO ANTI-CHOLINESTERASE ACTIVITIES BY PIPERINE, AN ALKALOID FROM THE SPICE FAMILY PIPERACEAEAbstract
The alkaloid piperine from the spice family Piperaceae has been reported to possess poly-pharmacological activities including anti-depressant and cognitive enhancing effects. It has been suggested that its neurocognitive benefits may be via its activity on the cholinergic system, particularly on the enzyme acetylcholinesterase (AChE), a pharmacological target for neurodegenerative disease such as Alzheimer’s disease (AD). The paucity of information on the potential mechanism of inhibition of acetylcholinesterase and butyrylcholinesterase (BuChE), also a primary target for drug development for the treatment of AD, prompted this in vitro investigation. Dose-dependent inhibition of AChE and BuChE by piperine was determined using a modified classic colorimetric method of Ellman. Kinetics of inhibition was determined by Lineweaver-Burk methods. Piperine inhibited both AChE and BuChE in a concentration dependent manner with IC50 values of 0.12 mM and 0.067mM, respectively. Piperine exhibited a higher selectivity towards BuChE with a BuChE/AChE ratio of 0.56mM. Kinetic values for AChE classify piperine as a competitive inhibitor whereas the values for BuChE classify it as a mixed inhibitor. Compared to galanthamine (a mixed competitive non-competitive AChEinhibitor, IC50 of 1.068 nmol/ml under similar assay conditions) we conclude that although the AChE inhibition by piperine is not as potent as that of galanthamine, in addition to its known antioxidant and anti-inflammatory activities, piperine could provide a novel poly-pharmacological lead of potential benefit for the symptomatic treatment of AD and therefore warrants further investigation.
E. J. Okello*, A. Coleman and C. J. Seal
Human Nutrition Research Centre, School of Agriculture, Food and Rural Development, Faculty of Science and Engineering, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom
08 October, 2014
28 July, 2015
22 August, 2015
01 September, 2015