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Ginsenoside Rg1 Prevents Chemotherapy-Induced Cognitive Impairment: Associations with Microglia-Mediated Cytokines, Neuroinflammation, and Neuroplasticity

  • Dong-Dong Shi
  • Yu-Hua Huang
  • Cora Sau Wan Lai
  • Celia M. Dong
  • Leon C. Ho
  • Xiao-Yang Li
  • Ed X. Wu
  • Qi Li
  • Xiao-Min Wang
  • Yong-Jun Chen
  • Sookja Kim Chung
  • Zhang-Jin ZhangEmail author
Article

Abstract

Chemotherapy-induced cognitive impairment, also known as “chemobrain,” is a common side effect. The purpose of this study was to examine whether ginsenoside Rg1, a ginseng-derived compound, could prevent chemobrain and its underlying mechanisms. A mouse model of chemobrain was developed with three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination at a 2-day interval. Rg1 (5 and 10 mg/kg daily) was given 1 week prior to DAC regimen for 3 weeks. An amount of 10 mg/kg Rg1 significantly improved chemobrain-like behavior in water maze test. In vivo neuroimaging revealed that Rg1 co-treatment reversed DAC-induced decreases in prefrontal and hippocampal neuronal activity and ameliorated cortical neuronal dendritic spine elimination. It normalized DAC-caused abnormalities in the expression of multiple neuroplasticity biomarkers in the two brain regions. Rg1 suppressed DAC-induced elevation of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but increased levels of the anti-inflammatory cytokines IL-4 and IL-10 in multiple sera and brain tissues. Rg1 also modulated cytokine mediators and inhibited DAC-induced microglial polarization from M2 to M1 phenotypes. In in vitro experiments, while impaired viability of PC12 neuroblastic cells and hyperactivation of BV-2 microglial cells, a model of neuroinflammation, were observed in the presence of DAC, Rg1 co-treatment strikingly reduced DAC’s neurotoxic effects and neuroinflammatory response. These results indicate that Rg1 exerts its anti-chemobrain effect in an association with the inhibition of neuroinflammation by modulating microglia-mediated cytokines and the related upstream mediators, protecting neuronal activity and promoting neuroplasticity in particular brain regions associated with cognition processing.

Keywords

Ginsenoside Rg1 Chemobrain Cytokines Neuroinflammation Neuroplasticity In vivo neuroimaging 

Notes

Acknowledgements

This study was supported by General Research Fund (GRF) of Research Grant Council of HKSAR (17115017 for Z.-J.Z.).

Compliance with Ethical Standards

Conflict of Interest Statement

All authors have no conflicts of interest with this work.

Supplementary material

12035_2019_1474_MOESM1_ESM.docx (537 kb)
ESM 1 (DOCX 536 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Dong-Dong Shi
    • 1
  • Yu-Hua Huang
    • 2
  • Cora Sau Wan Lai
    • 2
  • Celia M. Dong
    • 3
  • Leon C. Ho
    • 3
  • Xiao-Yang Li
    • 2
  • Ed X. Wu
    • 3
  • Qi Li
    • 4
  • Xiao-Min Wang
    • 5
  • Yong-Jun Chen
    • 6
  • Sookja Kim Chung
    • 2
  • Zhang-Jin Zhang
    • 1
    Email author
  1. 1.School of Chinese Medicine, LKS Faculty of MedicineThe University of Hong KongHong KongChina
  2. 2.School of Biomedical Sciences, State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of MedicineThe University of Hong KongHong KongChina
  3. 3.Laboratory of Biomedical Imaging and Signal Processing, Department of Electrical and Electronic EngineeringThe University of Hong KongHong KongChina
  4. 4.Department of Psychiatry, State Key Laboratory of Cognitive and Brain Sciences, HKU-SIRIThe University of Hong KongHong KongChina
  5. 5.Department of Anesthesiology, LKS Faculty of MedicineThe University of Hong KongHong KongChina
  6. 6.South China Research Center for Acupuncture and MoxibustionGuangzhou University of Chinese MedicineGuangzhouChina

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