IN-VITRO ANTI-CHOLINESTERASE ACTIVITIES BY PIPERINE, AN ALKALOID FROM THE SPICE FAMILY PIPERACEAE

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.