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Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells

  • Authors:
    • Xiaonan Wang
    • Bei Li
    • Xiaohong Yu
    • Ye Zhou
    • Kaile Wang
    • Yue Gao
  • View Affiliations / Copyright

    Affiliations: Department of Geriatric Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 16
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    Published online on: December 1, 2023
       https://doi.org/10.3892/mmr.2023.13139
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Abstract

Alzheimer's disease (AD) is the most common type of age‑related dementia, and causes progressive memory degradation, neuronal loss and brain atrophy. The pathological hallmarks of AD consist of amyloid‑β (Aβ) plaque accumulation and abnormal neurofibrillary tangles. Amyloid fibrils are constructed from Aβ peptides, which are recognized to assemble into toxic oligomers and exert cytotoxicity. The fibrillar Aβ‑protein fragment 25‑35 (Aβ25‑35) induces local inflammation, thereby exacerbating neuronal apoptosis. Notoginsenoside R1 (NGR1), one of the primary bioactive ingredients isolated from Panax notoginseng, exhibits effective anti‑inflammatory and anti‑oxidative activities. However, NGR1 pharmacotherapies targeting Aβ‑induced inflammation and cell injury cascade remain to be elucidated. The present study investigated the effect and mechanism of NGR1 in Aβ25‑35‑treated PC12 cells. NGR1 doses between 250 and 1,000 µg/ml significantly increased cell viability suppressed by 20 µM Aβ25‑35 peptide treatment. Notably, the present study demonstrated that Aβ25‑35 peptide‑induced sphingosine kinase 1 (SphK1) signaling activation was reduced after NGR1 treatment, further inhibiting the downstream NF‑κB inflammatory signaling pathway. In addition, administration of SphK1 inhibitor II (SKI‑II), a SphK1 inhibitor, also significantly reduced Aβ25‑35 peptide‑induced apoptosis and the ratio of NF‑κB p‑p65/p65. Furthermore, SphK1 knockdown in PC12 cells using small interfering RNA alleviated Aβ‑induced cell apoptosis and inflammation, suggesting a pivotal role of SphK1 signaling in the anti‑inflammatory effect of NGR1. In summary, NGR1 alleviated inflammation and apoptosis stimulated by Aβ25‑35 by inhibiting the SphK1/NF‑κB signaling pathway and may be a promising agent for future AD treatment.
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Spandidos Publications style
Wang X, Li B, Yu X, Zhou Y, Wang K and Gao Y: Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells. Mol Med Rep 29: 16, 2024.
APA
Wang, X., Li, B., Yu, X., Zhou, Y., Wang, K., & Gao, Y. (2024). Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells. Molecular Medicine Reports, 29, 16. https://doi.org/10.3892/mmr.2023.13139
MLA
Wang, X., Li, B., Yu, X., Zhou, Y., Wang, K., Gao, Y."Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells". Molecular Medicine Reports 29.1 (2024): 16.
Chicago
Wang, X., Li, B., Yu, X., Zhou, Y., Wang, K., Gao, Y."Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells". Molecular Medicine Reports 29, no. 1 (2024): 16. https://doi.org/10.3892/mmr.2023.13139
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Li B, Yu X, Zhou Y, Wang K and Gao Y: Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells. Mol Med Rep 29: 16, 2024.
APA
Wang, X., Li, B., Yu, X., Zhou, Y., Wang, K., & Gao, Y. (2024). Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells. Molecular Medicine Reports, 29, 16. https://doi.org/10.3892/mmr.2023.13139
MLA
Wang, X., Li, B., Yu, X., Zhou, Y., Wang, K., Gao, Y."Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells". Molecular Medicine Reports 29.1 (2024): 16.
Chicago
Wang, X., Li, B., Yu, X., Zhou, Y., Wang, K., Gao, Y."Notoginsenoside R1 ameliorates the inflammation induced by amyloid‑β by suppressing SphK1‑mediated NF‑κB activation in PC12 cells". Molecular Medicine Reports 29, no. 1 (2024): 16. https://doi.org/10.3892/mmr.2023.13139
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