Icariin Alleviates Diabetes-Associated Cognitive Dysfunction Through Modulation of LCN2-MEK/ERK Signaling-Associated...

Area of Science:

• Neuroscience
• Pharmacology
• Endocrinology

Background:

• Diabetes-associated cognitive dysfunction (DACD) is a severe complication with limited treatments.
• Icariin (ICA), a natural flavonoid, shows potential neuroprotective effects.
• Mechanisms of ICA in DACD are not fully understood.

Purpose of the Study:

• Investigate ICA's protective effects on DACD.
• Elucidate ICA's multi-target mechanisms, focusing on neuroinflammatory signaling.

Main Methods:

• Proteomics and ELISA to identify differentially expressed proteins in DACD patients.
• In vivo study: db/db mice treated with ICA, assessing cognitive function, hippocampal neuroinflammation, and LCN2-MEK/ERK pathway.
• In vitro study: High glucose-stimulated HT22 cells to validate the LCN2-MEK/ERK pathway's role via LCN2 knockdown.

Main Results:

• ICA improved spatial learning and memory in db/db mice.
• ICA reduced hippocampal neuroinflammation, LCN2 expression, and MEK/ERK pathway phosphorylation.
• In vitro, ICA counteracted high glucose-induced LCN2/MEK/ERK activation and inflammation; LCN2 knockdown abolished ICA's inhibitory effect on the pathway.

Conclusions:

• ICA ameliorates DACD by targeting the LCN2-MEK/ERK pathway and reducing neuroinflammation.
• ICA demonstrates protective effects against DACD.
• ICA holds potential for neurodegenerative disorders linked to metabolic dysregulation.