Ginsenoside Rg1 Attenuates Lipopolysaccharide-Induced Inflammatory Responses Via the Phospholipase C-γ1 Signaling Pathway in Murine BV-2 Microglial Cells

Author(s): Y. Zong, Q.-L. Ai, L.-M. Zhong, J.-N. Dai, P. Yang, Y. He, J. Sun, E.-A. Ling, D. Lu.

Journal Name: Current Medicinal Chemistry

Volume 19 , Issue 5 , 2012

Abstract:

Background and Purpose: Microglial activation plays an important role in neurodegenerative diseases by producing an array of proinflammatory enzymes and cytokines. Ginsenoside Rg1 (Rg1), a well-known Chinese herbal medicine, has been well recognized for its anti-inflammatory effect. This study sought to determine the anti-inflammatory effects of Rg1and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells.

Experimental Approach: Murine BV-2 microglial cells were treated with Rg1 (10, 20, and 40 μM) and/or LPS (1 μg·ml-1). The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR assay and double immunofluorescence labeling, respectively. Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP- responsive element (CRE)-binding protein (CREB) were measured by western blot. U73122 (5 μM), a specific phospholipase C (PLC) inhibitor, was used to determine if PLC signaling pathway might be involved in Rg1s action on activated BV-2 cells.

Key Results: Pretreatment with Rg1 significantly attenuated the LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor-κB (NF-κB) in BV-2 cells. U73122 blocked the effects of Rg1 on LPS-induced microglial activation. In addition, PLC-γ1 inhibition partially abolished the inhibitory effect of Rg1 on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK).

Conclusion and Implications: This investigation demonstrates that Rg1 significantly attenuates overactivation of microglial cells by repressing expression levels of neurotoxic proinflammatory mediators and cytokines via activation of PLC-γ1 signaling pathway.

Keywords: BV-2 cells, Ginsenoside Rg1, lipopolysaccharide, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, phospholipase C-γ1, mitogen-activated protein kinases, extracellular signal regulated kinase1/2, c-Jun N-terminal protein kinase, p38 mitogen-activated protein kinase, cyclic AMP-responsive element (CRE)-binding protein, nuclear factor-κB, inhibitor κB-α

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Article Details

VOLUME: 19
ISSUE: 5
Year: 2012
Page: [770 - 779]
Pages: 10
DOI: 10.2174/092986712798992066
Price: $58

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