Abstract

Icariin (ICA), a major flavonoid extracted from the Chinese tonic herb Epimedium, exerts beneficial effects in a variety of age-dependent diseases, such as Alzheimer's disease (AD). However, the anti-aging mechanisms remain unclear. The senescence-accelerated mouse-prone 8 (SAMP8) model has been used to study age-related neurodegenerative changes associated with aging and the pathogenesis of AD. Hence, the current study was designed to examine the effect of ICA on aging and behavioral improvement in SAMP8 mice and explore the role of autophagy in the ICA-mediated neuroprotection. SAMP8 mice were administered with ICA at the age of 5 months, and the treatment lasted for 3 consecutive months. Morris water maze was used to evaluate cognitive function. The SA-β-gal staining was utilized to determine the number of senescence cells. The neuronal morphological changes were examined via Nissl staining. The hippocampal neuronal ultrastructure was examined by transmission electron microscopy. The expression of autophagy protein was examined by Western blot. ICA exhibited a robust improvement in spatial learning and memory function of SAMP8 mice. Meanwhile, ICA reduced the number of senescence cells in the brain of SAMP8 mice, and inhibited neuronal loss and reversed neuronal structural changes in the hippocampus of SAMP8 mice. Moreover, ICA treatment also decreased formation of autophagosomes in the hippocampus of SAMP8 mice, and reduced the expression of autophagy-related proteins LC3-II and p62. These results demonstrate that ICA possesses the ability of delaying brain aging in SAMP8 mice, and the possible mechanism may be related to the regulation of autophagy.