Effects of Luteolin on Spatial Memory, Cell Proliferation, and Neuroblast Differentiation in the Hippocampal Dentate Gyrus in a Scopolamine-induced Amnesia Model

Objectives: Luteolin, a common flavonoid from many plants, has various pharmacological activities, including a memory-improving effect. In this study, we investigated the effects of luteolin on spatial memory, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a rat model of scopolamine (SCO)-induced amnesia.

Methods: Scopolamine was subcutaneously administered for 28 days via an Alzet minipump (44 mg/ml delivered at 2·5 μl/h) along with a daily intraperitoneal administration of vehicle (saline) 10 mg/kg luteolin or 5 mg/kg galantamine (GAL) (a control drug for acetylcholinesterase (AChE) inhibitor) for 28 days.

Results: The administration of SCO significantly decreased the spatial alteration percentage in the Y-maze test compared to that in the vehicle (saline)-treated group. The administration of luteolin or GAL significantly improved the spatial alteration percentage compared to that in the SCO-treated group. Similarly, the administration of SCO significantly decreased the cell proliferation (Ki67-positive cells) and neuroblast differentiation (doubleocortin-positive cells) in the dentate gyrus. The administration of luteolin or GAL significantly mitigated the SCO-induced reduction of Ki67- and doublecortin-immunoreactive cells in the dentate gyrus. In addition, the administration of luteolin significantly decreased the lipid peroxidation (malondialdehyde (MDA) levels) and increased the brain-derived neurotrophic factor (BDNF) and AChE levels in the hippocampal homogenates compared to the SCO-treated group.

Conclusion: These results suggest that the luteolin treatment improves the SCO-induced reduction of cell proliferation and neuroblast differentiation in the dentate gyrus. The mechanism underlying the amelioration of SCO-induced amnesia by luteolin may be associated with the increase in BDNF, acetylcholine, and the decrease in lipid peroxidation.