Icariin is Neuroprotective, Reducing Ferroptosis

In animal studies, icariin has been shown to favorably change the balance of microbial populations in the aging gut microbiome, and is modestly protective against a range of age-related declines. How exactly it operates remains to be seen, but given that it alters the gut microbiome, there are likely many relevant mechanisms that stem from the influence of the microbiome on cell function through the body. Researchers here note that icariin reduces a form of programmed cell death in the aged brain, a contributing cause of neurodegeneration.

Icariin (ICA) is a flavonoid compound. ICA has multifarious pharmacological effects such as anti-depression, improvement of ischemic brain injury, anti-dementia, and anti-aging. Research on Alzheimer's disease (AD) has found that ICA possesses certain effects, with diverse mechanisms. ICA can reduce amyloid-β deposition to improve the symptoms of AD animal models, and its mechanism of action may be associated with the regulation of PI3K/AKT. In the nervous system, ICA can antagonize the damaging effect of neurotoxins on neurons in the rat cortex and hippocampus, and its mechanisms may be achieved by inhibiting the activation of microglia cells, reducing the production of inflammatory cytokines, alleviating the damage of inflammatory transmitters to neurons, and improving the learning and memory abilities of mice.

In the research of AD, it has been found that ferroptosis of nerve cells is a major event of nerve injury, and glial cell death also plays an important regulatory role in AD. Apart from conventional oxidative stress regulation, P53 is one of the important proteins that induce ferroptosis. P53 and MDM2 combine into a complex to regulate SLC7A11C and mediate lipid peroxidation. In this study, we attempted to further explain the role, exact mechanism and target of ICA in treating AD from the ferroptosis perspective. We found that 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.

Link: https://doi.org/10.18632/aging.205144