Differential effects of ginsenosides on NO and TNF-α production by LPS-activated N9 microglia

Wu, Chun Fu; Bi, Xiu Li; Yang, Jing; Zhan, Jia; Dong, Ying; Wang, Jin Hui; Wang, Ji Ming; Zhang, Ruiwen; Li, Xian

doi:10.1016/j.intimp.2006.04.021

Cited by 135 publications

(97 citation statements)

References 24 publications

(25 reference statements)

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“…Analysis of 2 crucial intracellular TLR4 signaling proteins, IκBα and NF-κB, were chosen to investigate neuroinflammatory signaling in CHME-5 cells. LPSinduced NF-κB p65 activation was consistent with other microglial cell lines [28,[37][38][39] . Given the fact that many studies investigating microglial responses used the same dose of LPS (1 μg/mL), we are confident that CHME-5 cells were adequately treated to observe inflammatory responses [36,40,41] ; unlike the use of a lower dose of LPS (1 ng/mL), which failed to activate and release nitric oxide in CHME-5 cells [42] .…”

Section: Discussionsupporting

confidence: 86%

LPS-induced TLR4 neuroinflammatory signaling in CHME-5 microglial cells

Figueroa-Hall¹,

Anderson²,

Das³

et al. 2017

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Aim:In the field of neuroinflammation, identifying specific effects of pharmacological agents and other factors is problematic given the relative difficulty and expense in obtaining and culturing primary microglia. Immortalized microglial cell lines are very useful, but only a limited number have been characterized for inflammatory signaling. Therefore, characterization of lipopolysaccharide (LPS)-induced toll-like receptor 4 (TLR4) signaling in CHME-5, a microglial cell line, is expected to be of value as an experimental model of inflammatory signaling in the central nervous system (CNS). Methods: It was recently suggested that CHME-5 cells are of rat origin, not human, hence, verification of this claim using short tandem repeat genotype sequencing, along with immunoblotting, reverse transcription-polymerase chain reaction, and immunocytochemistry techniques to validate that CHME-5 retain morphological, phenotypical, and functional characteristics of primary microglia were undertaken. Results: LPS induced inhibitor kappa B-alpha and nuclear factorkappa B (NF-κB) p65 activation, NF-κB p65 binding activity, and tumor necrosis factor alpha gene expression. Additionally, results also confirmed the maintenance of microglial phenotype as seen with increased cluster of differentiation 68 gene and protein expression, immunofluorescence, and the absence of glial fibrillary acidic protein-immunoreactivity. Key words:Escherichia coli lipopolysaccharide, nuclear factor-kappa B p65, cluster of differentiation 68, toll-like receptor 4, neuroinflammation ABSTRACTArticle history:

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Section: Discussionsupporting

confidence: 86%

LPS-induced TLR4 neuroinflammatory signaling in CHME-5 microglial cells

Figueroa-Hall¹,

Anderson²,

Das³

et al. 2017

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“…Thus, P ginseng maintains both stimulatory and inhibitory effects, and in some situations even has a "hot" or stimulating effect, while P quinquefolium is "cool" or calming to the CNS. The protective effects of Rb1, Rg1, Rg3 and Rh2 on neurodegeneration are well reported [26][27][28][29][30] .…”

Section: Pharmacologymentioning

confidence: 99%

“…Rb1 inhibits leukotriene release, Rg1 increases the T-helper cell and stimulates immune activity in the aged, polysaccharide and PPT type ginsenosides enhance interferon production, phagocytosis, natural killer cells, B and T cells [44] . Rb1, Rg1 and Rg3 inhibit cytokine production, inhibit COX-2 gene expression, inhibit histamine release, stabilize neutrophils and lymphocytes [29,42,[45][46][47] .…”

Section: Pharmacologymentioning

confidence: 99%

Comparison of the pharmacological effects ofPanax ginsengandPanax quinquefolium

Chen¹,

Chiou²,

Zhang

2008

Acta Pharmacologica Sinica

231

139

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Medical application of Panax ginseng was first found in "Shen-Nong Herbal Classic" around 200 AD Panax quinquefolium was first introduced in "Essential of Materia Medica" in 1694 in China. The most important bioactive components contained in P ginseng and P quinquefolium are ginseng saponins (GS). The contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which was lower in P quinquefolium. After steaming for several hours, the total GS will decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase, while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation, especially in P quinquefolium, is high. P ginseng and P quinquefolium are general tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS) activities, but the effect of the latter is weaker. Thus, for the higher contents of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it. Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax, antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus, for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better than P quinquefolium. For anticancer effects, P quinquefolium is better.

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“…Microglial N9 cells by LPS-stimulation activate release of NO, which mediates inflammatory processes in CNS (18). To investigate potential neuroprotection of puerarin on microglia activation, we examined the effect of puerarin on the production of extracellular NO by Griess assay and intracellular NO by flow cytometry.…”

Section: Puerarin Inhibits Production Of No and Ros In N9 Cells Inducmentioning

confidence: 99%

“…NF-κB is an important transcription factor that regulates the transcription of many genes associated with inflammation, including the iNOS and ROS relative gene (4,18,21,23). Resting NF-κB is located in the cytoplasm, NF-κB rapidly transfers to the nucleus in response to stimuli and activates the transcription of proinflammation (23).…”

Section: Puerarin Exhibited Potent Inhibition On Activation and Transmentioning

confidence: 99%

Puerarin suppresses production of nitric oxide and inducible nitric oxide synthase in lipopolysaccharide-induced N9 microglial cells through regulating MAPK phosphorylation, O-GlcNAcylation and NF-κB translocation

Zheng

Yu²,

Yang

2012

Int J Oncol

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Abstract. Microglial cells play a critical role in mediating central nervous system inflammatory processes. Activated microglial cells induced by proinflammatory factor, such as lipopolysaccharide (LPS), release many kinds of neurotoxic cytokines including reactive oxygen species (ROS) which contributes to the pathogenesis of neurodegenerative diseases. Puerarin, extracted from kudzu root, possesses the characteristic of neuroprotection, antioxidation and anticancer. In the present study, we observed that LPS induced over-production of nitric oxide (NO) and increased the level of intracellular ROS in N9 microglial cells, but it was inhibited by puerarin. Furthermore, treatment with puerarin on N9 cells suppressed the over-expression of inducible nitric oxide synthase (iNOS) induced by LPS which is implicated in intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) level, phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathway. We also observed that the enhanced phosphorylation of p38, JNK and ERK1/2 in N9 cells induced by LPS were inhibited by puerarin, otherwise the down-regulation of O-GlcNAcylation level of protein in N9 cell induced by LPS was up-regulated by pretreatment with puerarin. These results indicate that puerarin effectively inhibits microglia activation induced by LPS through inhibiting expression of iNOS, production of NO and ROS which was mediated via regulating O-GlcNAcylation, phosphorylation of MAPK and NF-κB translocation. IntroductionMicroglial cells, macrophage-like cells in the central nervous system, participate in CNS immune response through releasing a variety of factors, including trophic factors and chemokines, to promote neuroprotection (1). Whereas under chronic inflammatory environment, excessive activation of microglia cells secrete cytotoxic substances and neurotoxic cytokines, such as reactive oxygen species (ROS) and nitric oxide (NO) which contribute to the pathogenesis of neurodegenerative diseases (2). Lipopolysaccharide (LPS), which consist in outer membrane of gram-negative bacteria as potent pro-inflammatory agents, induce microglial cell inflammatory injury through releasing proinflammatory mediators such as NO generated by inducible nitric oxide synthase (iNOS) (3,4). NO is considered as a main risk factor of progressive damage in neurodegenerative diseases (5,6). Microglia cell inflammatory response to LPS is involved in speedy regulation of many signal transduction molecules. The regulation of a signal pathway, such as mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB), is implicated in major molecular mechanisms of LPS-induced NO and ROS production in microglial cells (4,(6)(7)(8).O-Linked O-GlcNAcylation of protein, a single monosaccharide N-acetylglucosamine (GlcNAc) attached to the hydroxyl groups of specific serine or threonine residues, is an important post-translational modification on nuclear and cytoplasmic proteins (9,10). More than 500 proteins have been identified to be O-GlcNAcylated...

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Differential effects of ginsenosides on NO and TNF-α production by LPS-activated N9 microglia

Cited by 135 publications

References 24 publications

LPS-induced TLR4 neuroinflammatory signaling in CHME-5 microglial cells

LPS-induced TLR4 neuroinflammatory signaling in CHME-5 microglial cells

Comparison of the pharmacological effects ofPanax ginsengandPanax quinquefolium

Puerarin suppresses production of nitric oxide and inducible nitric oxide synthase in lipopolysaccharide-induced N9 microglial cells through regulating MAPK phosphorylation, O-GlcNAcylation and NF-κB translocation

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