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Hederagenin Upregulates PTPN1 Expression in Aβ-Stimulated Neuronal Cells, Exerting Anti-Oxidative Stress and Anti-Apoptotic Activities

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Abstract

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 Aβ25–35 (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.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Neurology, Nanyang First Peopleʼs Hospital, Nanyang, 473004, China

    Ke Li

  2. Department of Critical Care Medicine, Nanshi Hospital of Nanyang, Nanyang, 473010, China

    Yu Wang

  3. Department of Neurosurgery, the Affiliated Huaiʼan Hospital of Xuzhou Medical University, Huaiʼan Second Peopleʼs Hospital, #62 Huaihai South Road, Huaiʼan, 223300, China

    Hongzao Ni

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  1. Ke Li
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Ke Li, Yu Wang, and Hongzao Ni contributed to designing and performing experiments, collecting and analyzing the data, and writing the manuscript. All authors reviewed the manuscript.

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Correspondence to Hongzao Ni.

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Li, K., Wang, Y. & Ni, H. Hederagenin Upregulates PTPN1 Expression in Aβ-Stimulated Neuronal Cells, Exerting Anti-Oxidative Stress and Anti-Apoptotic Activities. J Mol Neurosci 73, 932–945 (2023). https://doi.org/10.1007/s12031-023-02160-9

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