Ginsenoside Rb1 attenuates lipopolysaccharide-induced chronic neuroinflammation in mice by tuning glial cell polarization |
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Institution: | 1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China;2. IK-Based Technology Innovation, Department of Science and Technology, Pretoria, 0001, South Africa |
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Abstract: | ObjectiveTo evaluate whether ginsenoside Rb1 (Rb1) can attenuate lipopolysaccharide (LPS)-induced chronic neuroinflammation in mice and to explore its relationship with glial cell polarization.MethodsIntraperitoneal injection with an escalating dose of LPS was used to establish a chronic neuroinflammation model in mice. Once LPS was initiated, 10 or 20 mg/kg Rb1, or sterile saline, was administered for 14 consecutive days. Open field test and beam walking test were used to monitor the changes in behavior. The concentration of cytokines in the serum and brain were used to monitor the systemic inflammation and neuroinflammation, respectively. Molecules specific to each glial cell phenotype were used to investigate glial cell polarization.ResultsMice in the LPS group had reduced spontaneous activities and impaired beam walking performance. Rb1 obviously eased LPS-induced behavior disturbances. Regarding the levels of serum cytokines, both tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly increased, while interleukin-10 (IL-10) and transforming growth factor β (TGF-β) remarkably decreased after LPS treatment (all P < .001). Rb1 treatment significantly attenuated LPS-induced serum cytokine changes (all P < .05). The results of quantitative polymerase chain reaction and western blotting showed that the mRNA and protein expression levels of TNF-α and complement component 3 (C3) in the brain were significantly increased after LPS treatment (all P < .01). Rb1 treatment significantly inhibited LPS-induced inflammation in the brain (all P < .05). Glial cell polarization analysis showed that M1 and M2 microglia, and A1 astrocytes increased following LPS treatment, while A2 astrocytes decreased. Rb1 treatment reduced M1 and M2 microglia, and A1 astrocytes, and significantly increased A2 astrocytes.ConclusionRb1 can attenuate chronic neuroinflammation induced by LPS in mice, which may be partially attributable to its fine tuning of microglia and astrocyte polarization. Rb1 has potential value for treating neurodegenerative diseases. |
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Keywords: | Astrocytes Chronic neuroinflammation Ginsenoside Rb1 Glial cell polarization Lipopolysaccharide Microglia Neurodegenerative diseases |
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