Effects of ginsenoside Re on LPS-induced inflammatory mediators in BV2 microglial cells

Kang-Woo Lee,Sun-Mi Choi,So Young Jung,Eun Jin Yang

doi:10.1186/1472-6882-12-196

Kang-Woo Lee, Sun-Mi Choi + Show 2 more

Open Access

https://doi.org/10.1186/1472-6882-12-196

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Abstract

BackgroundMicroglial activation plays an important role in neurodegenerative diseases by producing several pro-inflammatory enzymes and pro-inflammatory cytokines. Lipopolysaccharide (LPS)-induced inflammation leads to the activation of microglial cells in the central nervous system (CNS) and is associated with the pathological mechanisms of neurodegenerative diseases, including PD, AD, and ALS. Ginseng is a natural antioxidant used in herbal medicine and contains ginsenosides (Rb1, Rg1, Rg3, Re, and Rd), which have anti-neoplastic and anti-stress properties.This study demonstrates the involvement of the anti-inflammatory signaling pathway, ginsenoside-Re (G-Re), which is one of the ginsenosides mediated by LPS-induced neuroinflammation in BV2 microglial cells.MethodsBV2 microglial cells were pretreated with 2 μg/ml G-Re and stimulated with 1 μg/ml LPS to induce neuroinflammation. To investigate the effect of G-Re on LPS-induced cell signaling, we performed western blotting and immunofluorescence using specific antibodies, such as phospho-p38, COX2, and iNOS.ResultsPretreatment with 2 μg/ml G-Re was neuroprotective against 1 μg/ml LPS-treated microglial cells. The neuroprotective events induced by G-Re treatment in neuroinflammation occurred via the phospho-p38, iNOS, and COX2 signaling pathways in BV2 cells.ConclusionTaken together, we suggest that G-Re exerts a beneficial effect on neuroinflammatory events in neurodegenerative diseases.

Highlights

Microglial activation plays an important role in neurodegenerative diseases by producing several pro-inflammatory enzymes and pro-inflammatory cytokines
LPS stimulates nuclear factor-κB (NF-κB), cyclic AMP-responsive element-binding protein (CREB) and the mitogen-activated protein kinase (MAPKs) family, including extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38 MAPK [9], which have been implicated in the release of immune-related cytotoxic factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), and pro-inflammatory cytokines [4,10]
Ginsenosides-Re attenuates LPS-induced activation of p38MAPK in BV2 microglial cells Because the MAPK family is known to be a key player in LPS-induced cell signaling, we examined whether G-Re decreases the phosphorylation of the MAPK family proteins, JNK and p38MAPK

Summary

Introduction

Microglial activation plays an important role in neurodegenerative diseases by producing several pro-inflammatory enzymes and pro-inflammatory cytokines. Lipopolysaccharide (LPS)-induced inflammation leads to the activation of microglial cells in the central nervous system (CNS) and is associated with the pathological mechanisms of neurodegenerative diseases, including PD, AD, and ALS. A recent study has reported that the activation of microglia can trigger neurotoxicity via the production of pro-inflammatory and cytotoxic factors in neuronal cell lines treated with lipopolysaccharide (LPS), β-amyloid, glutamate, and arachidonate [5]. LPS stimulates nuclear factor-κB (NF-κB), cyclic AMP-responsive element-binding protein (CREB) and the mitogen-activated protein kinase (MAPKs) family, including extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38 MAPK [9], which have been implicated in the release of immune-related cytotoxic factors such as iNOS, COX2, and pro-inflammatory cytokines [4,10]. The control of microglial activation has been suggested as a promising therapeutic target to combat neurodegenerative diseases

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