Ginsenoside Rg1 Prevents Chemotherapy-Induced Cognitive Impairment: Associations with Microglia-Mediated Cytokines, Neuroinflammation, and Neuroplasticity.
In: Molecular neurobiology, Jg. 56 (2019-08-01), Heft 8, S. 5626-5642
Online
academicJournal
Zugriff:
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.
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Ginsenoside Rg1 Prevents Chemotherapy-Induced Cognitive Impairment: Associations with Microglia-Mediated Cytokines, Neuroinflammation, and Neuroplasticity.
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Autor/in / Beteiligte Person: | Shi, DD ; Huang, YH ; Lai, CSW ; Dong, CM ; Ho, LC ; Li, XY ; Wu, EX ; Li, Q ; Wang, XM ; Chen, YJ ; Chung, SK ; Zhang, ZJ |
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Zeitschrift: | Molecular neurobiology, Jg. 56 (2019-08-01), Heft 8, S. 5626-5642 |
Veröffentlichung: | Clifton, NJ : Humana Press, c1987-, 2019 |
Medientyp: | academicJournal |
ISSN: | 1559-1182 (electronic) |
DOI: | 10.1007/s12035-019-1474-9 |
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