Department of Neurology, Nanyang First People's Hospital, Nanyang, 473004, China.
Department of Critical Care Medicine, Nanshi Hospital of Nanyang, Nanyang, 473010, China.
J Mol Neurosci. 2023 Dec;73(11-12):932-945. doi: 10.1007/s12031-023-02160-9. Epub 2023 Oct 26.
Alzheimer's disease (AD) is a prevalently neurodegenerative disease characterized by neuronal damage which is associated with amyloid-β (Aβ) accumulation. Hederagenin is a triterpenoid saponin, exerting anti-apoptotic, anti-oxidative, anti-inflammatory, anti-tumoral, and neuroprotective activities. However, its role in AD progression is still obscure. The aim of this study was to explore the influences of hederagenin on Aβ-caused neuronal injury in vitro. Neuronal cells were treated with Aβ (Aβ) to establish a cellular model of AD. Cell viability was assessed using cell counting kit-8 (CCK-8). Oxidative stress was evaluated by detecting reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity. Apoptosis was investigated using TUNEL staining and caspase-3 activity assays. Protein tyrosine phosphatase nonreceptor type 1 (PTPN1) was screened by bioinformatics analysis. Protein levels of PTPN1 and protein kinase B (Akt) were measured by western blotting. Hederagenin (2.5, 5, and 10 μM) alone did not affect viability of neuronal cells, but relieved Aβ-induced viability reduction. Hederagenin mitigated Aβ-induced increase in ROS accumulation and decrease in SOD activity. Hederagenin attenuated Aβ-induced increase in apoptotic rate and caspase-3 activity. PTPN1 was screened as a target of hederagenin against AD by bioinformatics analysis. Hederagenin treatment resisted Aβ-induced decrease in PTPN1 mRNA and protein levels in neuronal cells. PTPN1 silencing attenuated the suppressive functions of hederagenin in Aβ-stimulated oxidative stress and apoptosis. Hederagenin mitigated Aβ-induced Akt signaling inactivation by upregulating PTPN1 expression. In conclusion, hederagenin attenuates oxidative stress and apoptosis in neuronal cells stimulated with Aβ by promoting PTPN1/Akt signaling activation.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征为神经元损伤，与淀粉样β（Aβ）积累有关。当药苷是一种五环三萜皂苷，具有抗凋亡、抗氧化、抗炎、抗肿瘤和神经保护作用。然而，其在 AD 进展中的作用尚不清楚。本研究旨在探讨当药苷对体外 Aβ引起的神经元损伤的影响。用 Aβ（Aβ）处理神经元细胞，建立 AD 细胞模型。用细胞计数试剂盒-8（CCK-8）评估细胞活力。通过检测活性氧（ROS）生成和超氧化物歧化酶（SOD）活性来评估氧化应激。用 TUNEL 染色和 caspase-3 活性测定法检测细胞凋亡。通过生物信息学分析筛选蛋白酪氨酸磷酸酶非受体型 1（PTPN1）。用 Western blot 法测定 PTPN1 和蛋白激酶 B（Akt）的蛋白水平。当药苷（2.5、5 和 10 μM）单独使用不会影响神经元细胞的活力，但可减轻 Aβ引起的活力降低。当药苷减轻了 Aβ引起的 ROS 积累增加和 SOD 活性降低。当药苷减轻了 Aβ引起的凋亡率和 caspase-3 活性增加。通过生物信息学分析筛选出当药苷是 AD 的靶点。当药苷处理可抵抗 Aβ诱导的神经元细胞中 PTPN1 mRNA 和蛋白水平的降低。PTPN1 沉默减弱了当药苷对 Aβ刺激的氧化应激和凋亡的抑制作用。当药苷通过上调 PTPN1 表达来减轻 Aβ诱导的 Akt 信号失活。综上所述，当药苷通过促进 PTPN1/Akt 信号激活来减轻 Aβ刺激的神经元细胞中的氧化应激和凋亡。
