Ilexgenin A Alleviated the Endoplasmic Reticulum Stress and Oxidative Stress-Induced Apoptosis in Amyloid-Beta25-35-Treated PC12 Cells

作者：Zhang, Jijuan^*; Bu, Ningning; Zhang, Hong; Shao, Haiyun; Sun, Chenghe

来源：JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS, 2023, 37(6): 3095-3104.

DOI：10.23812/j.biol.regul.homeost.agents.20233706.306

• Alzheimer's disease (AD)
• Ilexgenin A
• amyloid-beta (A0)25-35
• oxidative stress
• endoplasmic reticulum (ER) stress
• estrogen receptor 1 (ESR1)

Background: Ilexgenin A is a natural triterpenoid compound with a certain role in inflammation, atherosclerosis and tumor, and can regulate endoplasmic reticulum stress. The relevant effects of Ilexgenin A on Alzheimer's disease (AD) are discussed in the present study. Methods: Following the indicated transfection and treatment of Ilexgenin A (0.1, 1, 10 & mu;mol/L) or 25 & mu;mol/L amyloid-beta (A0)25-35, the assays of both 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry were adopted to estimate the viability and apoptosis of PC12 cells. Meanwhile, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and Reactive Oxygen Species (ROS) were determined by the assay kits of SOD and MDA and flow cytometry. Besides, the expressions of estrogen receptor 1 (ESR1), B-cell lymphoma-2 (Bcl-2), BCL2-Associated X protein (Bax), GlucoseRegulated Protein 78 (GRP78), C/EBP homologous protein (CHOP), and nuclear/cytoplasmic nuclear factor kappa B (NF-& kappa;B) p65 were quantified by Western blot or quantitative real-time polymerase chain reaction (qRT-PCR) as needed. Results: A025-35 decreased viability, promoted apoptosis, suppressed Bcl-2 and ESR1 protein expression levels, and enhanced the Bax protein level of PC12 cells (p < 0.001). Conversely, Ilexgenin A reversed the A025-35 effects on these aspects in PC12 cells (p < 0.05). Besides, A025-35 diminished SOD level and downregulated cytoplasmic NF-& kappa;B p65 protein expression while increased the levels of MDA, ROS and upregulated protein expressions of GRP78, CHOP, Caspase-12, nuclear NF-& kappa;B p65 (p < 0.001). On the other hand, Ilexgenin A exerted the opposite effects, which were overturned following the downregulation of Conclusions: In PC12 cells with the intervention of A025-35, which mimicked an in vitro AD model, Ilexgenin could alleviate the initiated oxidative stress and endoplasmic reticulum stress-induced apoptosis via upregulating ESR1.

• 单位
  1; 南方医科大学