Neuroprotective effect of Cubebin: A dibenzylbutyrolactone lignan on scopolamine-induced amnesia in mice

Background & objectives: Acetylcholinesterase (AChE) inhibitors represent a major class of drugs which provide symptomatic relief and improvement in cognitive function in Alzheimer's disease (AD). In this study, cubebin, a dibenzylbutyrolactone lignan, was isolated from Piper cubeba and investigated for its AChE inhibitory activity in an attempt to explore its potential for memory-enhancing activities in mice. Methods: Molecular docking of cubebin was carried out followed by in vitro AChE activity. Mice were treated with cubebin (25 & 50 mg/kg; i.p.), for three days and memory impairment was induced by scopolamine (3 mg/kg; i.p.). Memory function was evaluated by Morris water maze (MWM) test. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain. Results: Molecular docking study revealed that cubebin was well bound within the binding site of the AChE enzyme showing interactions such as pi-pi stacking and hydrogen bonding with residues present therein. Cubebin inhibited AChE enzyme in an in vitro assay with IC50 value of 992 mu M. Scopolamine administration caused a significant impairment of learning and memory in mice, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and oxidative stress in mice brain. Pre-treatment of cubebin (25 and 50 mg/kg; i.p.) significantly prevented scopolamine-induced learning and memory deficits along with attenuation of scopolamine- induced rise in brain AChE activity and oxidative stress level. Interpretation & conclusions: Cubebin showed promising protective activity in scopolamine- induced spatial memory impairment in mice. This could be attributed to its brain AChE inhibition and antioxidant activity.