Icariin improves cognitive deficits and activates quiescent neural stem cells in aging rats.

Ethnopharmacological Relevance: Icariin represents an important active component in Herba Epimedii, which is a famous Chinese herbal medicine that is widely used to treat some age-related diseases in oriental countries.

Objective: The aim of this work was to investigate the effects of icariin on cognitive function in natural aging rats, and then to explore its mechanism by investigating the activation of quiescent neural stem cells (NSCs) in the hippocampus.

Materials And Methods: Sprague-Dawley rats that were 18 months of age were divided into two groups including treated rats (i.e., icariin was administered from the age of 18 months to 21 months) and control rats (i.e., only saline was administered). The Morris water maze (MWM) tasks were then employed to measure spatial learning and memory. Subsequently, AraC was infused into the brain with osmotic minipumps in order to destroy proliferative stem cells primarily leaving quiescent NSCs. After seven days of recovery, 5-bromodeoxyuridine (BrdU) was co-labeled with markers for NSC to identify NSCs.

Results: The results from the MWM indicated that icariin has a beneficial effect on cognitive function in aging rats. In addition, by double-labeling BrdU and glial fibrillary acidic protein (GFAP), our findings indicated that NSC activation is markedly increased in the icariin-treated rats compared to control rats. For example, a much greater increase was produced in BrdU and highly polysialylated neural cell adhesion molecule (PSA-NCAM) and BrdU and Olig2 double-labeled cells following icariin treatment.

Conclusion: Our findings suggest that icariin represents a promising candidate for the modulation of aging. Therefore, icariin administration may effectively prevent or delay the onset of age-related cognitive degeneration, and its capability to activate quiescent NSCs may potentially be one of its mechanisms.