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Title: Ginsenoside Rg1 exerts anti-inflammatory effects via G protein-coupled estrogen receptor in lipopolysaccharide-induced microglia activation
Authors: Gao, XQ
Du, ZR
Yuan, LJ
Zhang, WD
Chen, L
Teng, JJ
Wong, MS 
Xie, JX
Chen, WF
Keywords: Ginsenoside rg1
G protein-coupled estrogen receptor
Microglial cells
Issue Date: 2019
Publisher: Frontiers Research Foundation
Source: Frontiers in neuroscience, 7 Nov. 2019, v. 13, 1168, p. 1-14 How to cite?
Journal: Frontiers in neuroscience 
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-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), 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-kappa B) 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.
ISSN: 1662-453X
DOI: 10.3389/fnins.2019.01168
Rights: Copyright © 2019 Gao, Du, Yuan, Zhang, Chen, Teng, Wong, Xie and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) ( The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Gao X-Q, Du Z-R, Yuan L-J, Zhang W-D, Chen L, Teng J-J, Wong M-S, Xie J-X and Chen W-F (2019) Ginsenoside Rg1 Exerts Anti-inflammatory Effects via G Protein-Coupled Estrogen Receptor in Lipopolysaccharide-Induced Microglia Activation. Front. Neurosci. 13:1168, 1-14 is available at
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