Icariin improves cognitive impairment by inhibiting ferroptosis of nerve cells

Aim: We investigated the effect and mechanism of Icariin (ICA) on improving neurobehavioral ability of mice with Alzheimer's disease (AD). Methods: We selected 10-month-old APP/PS1 mice (AD) and wild-type C57BL/6J mice (Normal). After intragastric administration of ICA, Morris water maze was employed to detect neurobehavioral improvements, and to assay key ferroptosis indicators and oxidative stress levels. The common target of ICA for resisting ferroptosis and AD was predicted by network pharmacology. Results: ICA could improve the neurobehavioral, memory and motor abilities of AD mice. It could lower the ferroptosis level and enhance the resistance to oxidative stress. After inhibition of MDM2, ICA could no longer improve the cognitive ability of AD mice, nor could it further inhibit ferroptosis. Network pharmacological analysis revealed that MDM2 might be the target of ICA action. Conclusions: We found that ICA can inhibit ferroptosis of nerve cells, thereby ameliorating neural damage in mice with AD.