Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside compound K reduces ischemia/reperfusion-induced neuronal apoptosis by inhibiting PTP1B-mediated IRS1 tyrosine dephosphorylation

  • Jing, Fu (Department of Rehabilitation, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Liang, Yu (Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Qian, Yu (Department of Rehabilitation, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Nengwei, Yu (Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Fei, Xu (Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Suping, Li (Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital)
  • Received : 2022.05.17
  • Accepted : 2022.08.25
  • Published : 2023.03.02
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Abstract

Background: Ginsenoside compound K (CK) stimulated activation of the PI3K-Akt signaling is one of the major mechanisms in promoting cell survival after stroke. However, the underlying mediators remain poorly understood. This study aimed to explore the docking protein of ginsenoside CK mediating the neuroprotective effects. Materials and methods: Molecular docking, surface plasmon resonance, and cellular thermal shift assay were performed to explore ginsenoside CK interacting proteins. Neuroscreen-1 cells and middle cerebral artery occlusion (MCAO) model in rats were utilized as in-vitro and in-vivo models. Results: Ginsenoside CK interacted with recombinant human PTP1B protein and impaired its tyrosine phosphatase activity. Pathway and process enrichment analysis confirmed the involvement of PTP1B and its interacting proteins in PI3K-Akt signaling pathway. PTP1B overexpression reduced the tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) after oxygen-glucose deprivation/reoxygenation (OGD/R) in neuroscreen-1 cells. These regulations were confirmed in the ipsilateral ischemic hemisphere of the rat brains after MCAO/R. Ginsenoside CK treatment reversed these alterations and attenuated neuronal apoptosis. Conclusion: Ginsenoside CK binds to PTP1B with a high affinity and inhibits PTP1B-mediated IRS1 tyrosine dephosphorylation. This novel mechanism helps explain the role of ginsenoside CK in activating the neuronal protective PI3K-Akt signaling pathway after ischemia-reperfusion injury.

Keywords

Acknowledgement

All persons who have made substantial contributions to the work reported in the manuscript (e.g., technical help, writing and editing assistance, general support), but who do not meet the criteria for authorship, are named in the Acknowledgements and have given us their written permission to be named. If we have not included an Acknowledgements, then that indicates that we have not received substantial contributions from non-authors.

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