Neuroprotective Effect of Icariin in App/Ps1 Transgenic Mice by Regulating Autophagy-Lysosome Processes Via Pi3k/Akt Pathway

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive brain damage and the development of dementia. Icariin (ICA), a primary bioactive compound found in the medicinal herb Epimedium, has been shown to improve cognitive impairment in AD. However, the underlying mechanisms of its neuroprotective effects still remain unclear. This study aimed to investigate the effects of ICA on the learning and memory capabilities of APP/PS1 double transgenic mice using network-pharmacology and in vivo experimental verification. Behavioral tests confirmed that ICA significantly improved learning and spatial memory in APP/PS1 mice. Nissl staining and immunofluorescence analysis revealed a reduction in amyloid plaque intensity, phosphorylated Tau protein, neuronal apoptosis, and oxidative stress following ICA treatment. Further studies indicated that ICA may promote the degradation of insoluble LC3B-II and p62, while increasing the expression of the lysosomal marker Lamp1. These findings suggest that ICA may improve lysosomal function and promote autophagosome-lysosome fusion to exert its neuroprotective effects via the PI3K/AKT signaling pathway, highlighting the potential of ICA in brain diseases.

Note:
Funding declaration: We thank the financial support from the National Natural Science Foundation of China (No. 21904110, 81973918, 82074505) and the Natural Science Foundation of Guangdong Province (No. 2023A1515011835) as well as science and technology program of Guangzhou (No. 202201011195).

Conflict of Interests: The authors have declared no conflict of interest to this study.

Ethical Approval: All animal procedures, care, and treatment were approved by the Ethics Committee of Guangzhou University of Chinese Medicine and the Regulations on the Management of Laboratory Animals.

Keywords: Alzheimer's disease, Icariin, Autophagy, Lysosome, PI3K/AKT pathway