Abstract
Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson’s disease. Ginsenoside Rg1, the most active ingredient of ginseng, has been reported to exert neuroprotective effects via estrogen and glucocorticoid receptors. The present study evaluated the involvement of the G protein-coupled estrogen receptor (GPER) in the anti-inflammatory effects of ginsenoside Rg1 against lipopolysaccharide (LPS)-induced microglia activation in the BV2 microglial cell line and ventral mesencephalic primary microglial culture. The pharmacological blockade and lentivirus-mediated small interfering RNA (siRNA) knockdown of GPER were used to study the underlying mechanism. Rg1 attenuated LPS-induced upregulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA and protein levels. The GPER antagonist G15 blocked the inhibitory effects of Rg1 and the GPER-specific agonist G1 on LPS-induced microglia activation. Rg1 mimicked the effects of G1 by inhibiting the LPS-induced activation of nuclear transcription factor-kappa B (NF-κB) and mitogen activated protein kinase signaling pathways, which was also blocked by G15. Moreover, lentivirus-mediated siRNA knockdown of GPER inhibited the anti-inflammatory effects of Rg1. Taken together, our results indicate that GPER is involved in the anti-inflammatory effects of Rg1 against LPS-induced microglia activation. These findings provide a new biological target of Rg1 for the treatment of neuroinflammatory disorders.
Highlights
Several studies have suggested that neuroinflammation plays an important role in the etiology of neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and encephalitides (Nolan et al, 2013; Heppner et al, 2015; Borjini et al, 2016; Schwartz and Deczkowska, 2016)
To demonstrate the anti-inflammatory effects of Rg1, the mRNA expressions of tumor necrosis factor-α (TNF-α), IL-1β, inducible nitric oxide synthase (iNOS), and COX-2 were detected by real-time PCR
The mRNA expressions of TNF-α, IL-1β, iNOS, and COX-2 were significantly increased in LPS-treated BV2 microglial cells when compared to the control group
Summary
Several studies have suggested that neuroinflammation plays an important role in the etiology of neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and encephalitides (Nolan et al, 2013; Heppner et al, 2015; Borjini et al, 2016; Schwartz and Deczkowska, 2016). The genomic effect of estrogen is mediated by the classical nuclear receptors ERα and ERβ (Prossnitz and Arterburn, 2015). The GPER mediates the non-genomic effect of estrogen and plays an important role in the antiinflammatory and anti-apoptotic effects of estrogen (Tamaki et al, 2014; Zhao et al, 2016). G1, a GPER selective agonist, can inhibit the production of LPS-induced cytokines in the animal model of multiple sclerosis and Parkinson’s disease (Blasko et al, 2009; Mendes-Oliveira et al, 2017). This arouses the possibility that the anti-inflammatory function of GPER could be exploited in the treatment of neuroinflammatory diseases
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