Antagonizing effect of icaritin on apoptosis and injury of hippocampal neurocytes induced by amyloid beta via GR/BDNF signaling pathway

Abstract

Purpose: Amyloid beta is the main component of senile plaques deposited in the hippocampus of people with Alzheimer’s disease (AD), with neurotoxicity and pro-apoptotic characteristics. Icaritin (ICA) has been found to have the properties of plerosis, regeneration, and anti-apoptosis in the neurocytes, its effects on Aβ-induced hippocampal neurocytes were studied in this research.

Methods: Different concentrations of Aβ_25–35 were used to treat mouse hippocampal neuron HT22 cells to determine the optimal concentration for constructing AD model; different concentrations of ICA were used to pretreat HT22 cells to explore their effects on cell activity. Cell injury was evaluated by measuring the viability and apoptosis of HT22 cells using MTT assay, and Annexin V/PI and Hoechst 33342 staining, respectively. Western blot and qPCR were performed to detect the expressions of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), and apoptosis-related factors. Oxidative stress was assessed by the biochemical analysis of Lactate dehydrogenase (LDH) release and superoxidase dismutase (SOD) activity.

Results: Aβ_25–35 inhibited the viability of HT22 cells and the expression of GR and BDNF in HT22 cells in a concentration-dependent manner. ICA at 20 µmol/L (ICA20) the most significantly increased the viability of HT22 cells and the expressions of GR and BDNF in HT22 cells. ICA20 increased viability, inhibited apoptosis and LDH release, promoted SOD activity and the expressions of GR, BDNF and Bcl-2, and inhibited the expressions of Bax and C Caspase-3 in AD. More importantly, shRNA-GR reversed the positive effects of ICA20 on AD.

Conclusions: ICA protected hippocampal neurocytes against Aβ_25–35 via GR/BDNF signaling pathway.

Keywords:

• Amyloid beta
• Alzheimer’s disease
• icaritin
• neuroprotective effect
• GR
• BDNF

Disclosure statement

The authors report no conflict of interest.

Data availability statement

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.