Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rd protects cerebral endothelial cells from oxygen-glucose deprivation/reoxygenation induced pyroptosis via inhibiting SLC5A1 mediated sodium influx

  • Li, Suping (Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Yu, Nengwei (Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Xu, Fei (Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Yu, Liang (Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Yu, Qian (Department of Rehabilitation, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital) ;
  • Fu, Jing (Department of Rehabilitation, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital)
  • Received : 2022.02.14
  • Accepted : 2022.05.12
  • Published : 2022.09.01
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Abstract

Background: Ginsenoside Rd is a natural compound with promising neuroprotective effects. However, the underlying mechanisms are still not well-understood. In this study, we explored whether ginsenoside Rd exerts protective effects on cerebral endothelial cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and its potential docking proteins related to the underlying regulations. Method: Commercially available primary human brain microvessel endothelial cells (HBMECs) were used for in vitro OGD/R studies. Cell viability, pyroptosis-associated protein expression and tight junction protein degradation were evaluated. Molecular docking proteins were predicted. Subsequent surface plasmon resonance (SPR) technology was utilized for validation. Flow cytometry was performed to quantify caspase-1 positive and PI positive (caspase-1+/PI+) pyroptotic cells. Results: Ginsenoside Rd treatment attenuated OGD/R-induced damage of blood-brain barrier (BBB) integrity in vitro. It suppressed NLRP3 inflammasome activation (increased expression of NLRP3, cleaved caspase-1, IL-1β and GSDMD-N terminal (NT)) and subsequent cellular pyroptosis (caspase-1+/PI + cells). Ginsenoside Rd interacted with SLC5A1 with a high affinity and reduced OGD/R-induced sodium influx and potassium efflux in HBMECs. Inhibiting SLC5A1 using phlorizin suppressed OGD/R-activated NLRP3 inflammasome and pyroptosis in HBMECs. Conclusion: Ginsenoside Rd protects HBMECs from OGD/R-induced injury partially via binding to SLC5A1, reducing OGD/R-induced sodium influx and potassium efflux, thereby alleviating NLRP3 inflammasome activation and pyroptosis.

Keywords

Acknowledgement

This study was supported by the Key Research Project of the Science & Technology Department of Sichuan Province, China (2021YFS0131 and 2020YFS0414).

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