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

Mol Neurobiol. 2019 Aug;56(8):5626-5642. doi: 10.1007/s12035-019-1474-9. Epub 2019 Jan 18.


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: Chemobrain; Cytokines; Ginsenoside Rg1; In vivo neuroimaging; Neuroinflammation; Neuroplasticity.

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Anxiety / complications
  • Anxiety / physiopathology
  • Behavior, Animal
  • Biomarkers / blood
  • Brain / drug effects
  • Brain / pathology*
  • Brain / physiopathology
  • Cognition / drug effects
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / physiopathology
  • Cognitive Dysfunction / prevention & control*
  • Cytokines / blood
  • Cytokines / metabolism*
  • Dendritic Spines / drug effects
  • Dendritic Spines / pathology
  • Female
  • Ginsenosides / pharmacology
  • Ginsenosides / therapeutic use*
  • Glial Fibrillary Acidic Protein / metabolism
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Locomotion / drug effects
  • Magnetic Resonance Imaging
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / drug effects
  • Microglia / pathology*
  • Neuronal Plasticity* / drug effects
  • PC12 Cells
  • Rats


  • Antineoplastic Agents
  • Biomarkers
  • Cytokines
  • Ginsenosides
  • Glial Fibrillary Acidic Protein
  • ginsenoside Rg1