Fang Houying, Tian Hao, Liu Jianlin, Peng Tao, Wang Dan
Department of Neurology, Hubei NO.3 People(')s Hospital of Jianghan University, Wuhan, Hubei, 430000, China.
Department of Neurology, Hubei NO.3 People(')s Hospital of Jianghan University, Wuhan, Hubei, 430000, China.
Neuroscience. 2025 Jan 26;565:377-385. doi: 10.1016/j.neuroscience.2024.12.011. Epub 2024 Dec 7.
Ginsenoside Rg1 (Rg1) has been shown to treat a variety of human diseases, including Alzheimer's disease (AD). However, its mechanism in AD needs further investigation. Microglial cells (BV2) were treated with Aβ to induce AD cell models. Cell viability and apoptosis were tested by cell counting kit 8 assay and flow cytometry. The protein levels of GATA-binding protein 4 (GATA4), phosphodiesterase 4A (PDE4A), autophagy-related markers, M1/M2 polarization-related markers and PI3K/AKT-related markers were detected by western blot. Inflammation factors were detected by ELISA. Jaspar and dual-luciferase reporter assay were used to evaluate the interaction between GATA4 and PDE4A. Our results showed that Rg1 promoted viability and autophagy, while suppressed apoptosis and inflammation in Aβ-induced BV2 cells. Rg1 reduced GATA4 protein expression, and GATA4 upregulation reversed the regulation of Rg1 on Aβ-induced BV2 cell injury. GATA4 interacted with PDE4A, and GATA4 facilitated Aβ-induced BV2 cell injury by increasing PDE4A expression. Besides, GATA4 knockdown reduced PDE4A protein expression and inactivated PI3K/AKT axis, while these effects were abolished by PDE4A overexpression. In conclusion, our data suggested that Ginsenoside Rg1 inhibited microglial cell apoptosis and inflammation to attenuate AD progression by regulating the GATA4/PDE4A/PI3K/AKT axis.
人参皂苷Rg1（Rg1）已被证明可治疗多种人类疾病，包括阿尔茨海默病（AD）。然而，其在AD中的作用机制仍需进一步研究。用β淀粉样蛋白（Aβ）处理小胶质细胞（BV2）以诱导AD细胞模型。通过细胞计数试剂盒8检测和流式细胞术检测细胞活力和凋亡情况。通过蛋白质印迹法检测GATA结合蛋白4（GATA4）、磷酸二酯酶4A（PDE4A）、自噬相关标志物、M1/M2极化相关标志物和PI3K/AKT相关标志物的蛋白水平。通过酶联免疫吸附测定法检测炎症因子。使用Jaspar和双荧光素酶报告基因检测法评估GATA4与PDE4A之间的相互作用。我们的结果表明，Rg1可促进Aβ诱导的BV2细胞的活力和自噬，同时抑制其凋亡和炎症。Rg1降低了GATA4蛋白表达，而GATA4的上调逆转了Rg1对Aβ诱导的BV2细胞损伤的调节作用。GATA4与PDE4A相互作用，并且GATA4通过增加PDE4A表达促进Aβ诱导的BV2细胞损伤。此外，敲低GATA4可降低PDE4A蛋白表达并使PI3K/AKT轴失活，而PDE4A的过表达消除了这些作用。总之，我们的数据表明人参皂苷Rg1通过调节GATA4/PDE4A/PI3K/AKT轴抑制小胶质细胞凋亡和炎症，从而减轻AD的进展。
