Nodakenin Enhances Cognitive Function and Adult Hippocampal Neurogenesis in Mice.

In our previous study, we demonstrated that nodakenin, a coumarin compound isolated from Angelica decursiva, ameliorates learning and memory impairments induced by scopolamine. In the present study, we investigated the effects of nodakenin on the cognitive function in the normal naïve mice in a passive avoidance task, and the results showed that nodakenin significantly increased the latency time in normal naïve mice. In addition, sub-chronic administration of nodakenin increased the number of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the hippocampal dentate gyrus (DG) region. The percentage of BrdU and NeuN (neuronal cell marker)-immunopositive cells was also significantly increased by the nodakenin administration. Western blotting results showed that the expression levels of phosphorylated protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3β (GSK-3β) were significantly increased in hippocampal tissue by sub-chronic nodakenin administration. These findings suggest that the sub-chronic administration of nodakenin enhances adult hippocampal neurogenesis in the DG region via Akt-GSK-3β signaling and this increase may be associated with nodakenin's positive effect on cognitive processing.