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Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase C-γ1 signaling pathway in murine BV-2 microglial cells.
Curr Med Chem. 2012; 19(5):770-9.CM

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 Rg1 and 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.

Authors+Show Affiliations

Department of Anatomy, Kunming Medical University, Kunming, Yunnan, 650500, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22214447

Citation

Zong, Y, et al. "Ginsenoside Rg1 Attenuates Lipopolysaccharide-induced Inflammatory Responses Via the Phospholipase C-γ1 Signaling Pathway in Murine BV-2 Microglial Cells." Current Medicinal Chemistry, vol. 19, no. 5, 2012, pp. 770-9.
Zong Y, Ai QL, Zhong LM, et al. Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase C-γ1 signaling pathway in murine BV-2 microglial cells. Curr Med Chem. 2012;19(5):770-9.
Zong, Y., Ai, Q. L., Zhong, L. M., Dai, J. N., Yang, P., He, Y., Sun, J., Ling, E. A., & Lu, D. (2012). Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase C-γ1 signaling pathway in murine BV-2 microglial cells. Current Medicinal Chemistry, 19(5), 770-9.
Zong Y, et al. Ginsenoside Rg1 Attenuates Lipopolysaccharide-induced Inflammatory Responses Via the Phospholipase C-γ1 Signaling Pathway in Murine BV-2 Microglial Cells. Curr Med Chem. 2012;19(5):770-9. PubMed PMID: 22214447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase C-γ1 signaling pathway in murine BV-2 microglial cells. AU - Zong,Y, AU - Ai,Q-L, AU - Zhong,L-M, AU - Dai,J-N, AU - Yang,P, AU - He,Y, AU - Sun,J, AU - Ling,E-A, AU - Lu,D, PY - 2011/09/01/received PY - 2011/12/15/accepted PY - 2012/1/5/entrez PY - 2012/1/5/pubmed PY - 2012/7/24/medline SP - 770 EP - 9 JF - Current medicinal chemistry JO - Curr Med Chem VL - 19 IS - 5 N2 - 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 Rg1 and 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. SN - 1875-533X UR - https://www.unboundmedicine.com/medline/citation/22214447/Ginsenoside_Rg1_attenuates_lipopolysaccharide_induced_inflammatory_responses_via_the_phospholipase_C_γ1_signaling_pathway_in_murine_BV_2_microglial_cells_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=0929-8673&volume=19&issue=5&spage=770&aulast=Zong DB - PRIME DP - Unbound Medicine ER -