Details

Autor(en) / Beteiligte

• Zong, Y
• Ai, Q-L
• Zhong, L-M
• Dai, J-N
• Yang, P
• He, Y
• Sun, J
• Ling, E-A
• Lu, D

Titel

Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase C-γ1 signaling pathway in murine BV-2 microglial cells

Ist Teil von

• Current medicinal chemistry, 2012-02, Vol.19 (5), p.770-779

Ort / Verlag

United Arab Emirates

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Rg1 and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells. 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. 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). 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.