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 Aβ25–35 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: Aβ25–35 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 Aβ25–35 via GR/BDNF signaling pathway.

中文翻译：

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淫羊藿苷通过GR/BDNF信号通路拮抗β淀粉样蛋白诱导的海马神经细胞凋亡和损伤

摘要 目的：β淀粉样蛋白是阿尔茨海默病（AD）患者海马区老年斑的主要成分，具有神经毒性和促凋亡特征。已发现淫羊藿苷（ICA）在神经细胞中具有增殖、再生和抗凋亡的特性，本研究研究了其对 Aβ 诱导的海马神经细胞的影响。方法：用不同浓度的Aβ25-35处理小鼠海马神经元HT22细胞，确定构建AD模型的最佳浓度；不同浓度的 ICA 用于预处理 HT22 细胞，以探索它们对细胞活性的影响。通过分别使用 MTT 法、Annexin V/PI 和 Hoechst 33342 染色测量 HT22 细胞的活力和凋亡来评估细胞损伤。进行Western blot和qPCR检测糖皮质激素受体（GR）、脑源性神经营养因子（BDNF）和凋亡相关因子的表达。通过乳酸脱氢酶 (LDH) 释放和超氧化物歧化酶 (SOD) 活性的生化分析评估氧化应激。结果：Aβ25-35以浓度依赖性方式抑制HT22细胞的活力以及HT22细胞中GR和BDNF的表达。20 µmol/L (ICA20) 的 ICA 最显着增加 HT22 细胞的活力以及 HT22 细胞中 GR 和 BDNF 的表达。ICA20在AD中增加活力，抑制细胞凋亡和LDH释放，促进SOD活性和GR、BDNF和Bcl-2的表达，并抑制Bax和Caspase-3的表达。更重要的是，shRNA-GR 逆转了 ICA20 对 AD 的积极影响。结论：