Icariin Attenuates Amyloid-β (Aβ)-Induced Neuronal Insulin Resistance Through PTEN Downregulation

Abstract

Neuronal insulin resistance is implicated in neurodegenerative diseases. Icariin has been reported to improve insulin resistance in skeletal muscle cells and to restore impaired hypothalamic insulin signaling in the rats with chronic unpredictable mild stress. In addition, icariin can exert the neuroprotective effects in the mouse models of neurodegenerative diseases. However, the molecular mechanisms by which icariin affects neuronal insulin resistance are poorly understood. In the present study, amyloid-b (Ab) was used to induce insulin resistance in human neuroblastoma SK-N-MC cells. Insulin sensitivity was evaluated by measuring insulin-stimulated Akt T308 phosphorylation and glucose uptake. We found that the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mediated Ab-induced insulin resistance. Icariin treatment markedly reduced Ab-enhanced PTEN protein levels, leading to an improvement in Abinduced insulin resistance. Accordingly, PTEN overexpression obviously abolished the protective effects of icariin on Ab-induced insulin resistance. Furthermore, icariin activated proteasome activity. The proteasome inhibitor MG132 attenuated the effects of icariin on PTEN protein levels. Taken together, these results suggest that icariin protects SK-N-MC cells against Ab-induced insulin resistance by activating the proteasome-dependent degradation of PTEN. These findings provide an experimental background for the identification of novel molecular targets of icariin, which may help in the development of alternative therapeutic approaches for neurodegenerative diseases.

PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease

“…A recent in vivo study suggested that the promotion effect of ICA on proliferation and differentiation of hippocampal neural stem cells in AD model is related to the BDNF-tyrosine kinase B (TrkB)-ERK/AKT signaling pathway ( Lu et al, 2020 ). Moreover, ICA treatment significantly enhanced proteasome-dependent degradation of PTEN and protected SK-N-MC cells from Aβ-induced insulin resistance ( Zou et al, 2020 ). In addition, by down-regulating the expression of β-site amyloid precursor protein (APP) cleavage enzyme 1, icariin could decrease the deposition of β-amyloid peptide ( Wu et al, 2020 ).…”

Icariin Ameliorates Diabetic Renal Tubulointerstitial Fibrosis by Restoring Autophagy via Regulation of the miR-192-5p/GLP-1R Pathway

“…Icariin (ICA) is a major constituent of a flavonoid isolated from the plant Herba epimedii. A wide range of pharmacological effects has been attributed to ICA, including: improvement in neuronal insulin resistance Zou et al (2020) and testicular dysfunction (Zhao et al, 2020); protection of hippocampal neurons Liu et al (2019) and nucleus pulposus cells (Hua et al, 2020); potential against Alzheimer's Disease (Angeloni et al, 2019); and notably, as a traditional Chinese medicine, nourishment of the kidney and reinforcement of Yang. Recent research has demonstrated that ICA treatment reduces blood glucose levels in type 2 diabetic rats and protects pancreatic function Han et al (2015), Li et al (2020), Zhang and Qiu (2020), suggesting that ICA has an anti-T2DM effect. However, the exact mechanism of ICA on T2DN is yet unknown.…”

Icariin improves brain function decline in aging rats by enhancing neuronal autophagy through the AMPK/mTOR/ULK1 pathway

“…Icariin, as a major bioactive component for both Chinese herb and formula has been found to evoke the neuroprotective effects both in vivo and in vitro (Zou et al 2020). For instances, icariin can improve learning dysfunction, and restore synaptic and cognitive deficits in AD mice (Urano and Tohda 2010;Chen et al 2016;Sheng et al 2017).…”