Ginsenoside Rg1 Attenuates Lipopolysaccharide-Induced Inflammatory Responses Via the Phospholipase C-γ1 Signaling Pathway in Murine BV-2 Microglial Cells
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 Rg1's 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; c-Jun N-terminal protein kinase; cyclic AMP-responsive element (CRE)-binding protein; cyclooxygenase-2; extracellular signal regulated kinase1/2; inducible nitric oxide synthase; interleukin-1β; lipopolysaccharide; mitogen-activated protein kinases; nuclear factor-κB inhibitor κB-α; p38 mitogen-activated protein kinase; phospholipase C-γ1; tumor necrosis factor-α
Document Type: Research Article
Publication date: February 1, 2012
- Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.