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KMID : 0606920090170010070
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Biomolecules & Therapeutics
2009 Volume.17 No. 1 p.70 ~ p.78
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Inhibitory Effects of Coptis japonica Alkaloids on the LPS-Induced Activation of BV2 Microglial Cells
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Jeon Se-Jin
Ko Kwang-Ho
Ryu Jong-Hoon
Min Byung-Sun
Cheong Jae-Hoon
Han Seol-Heui
Kwon Kyung-Ja
Shin Sun-Mi
Lee Sung-Hoon
Rhee So-Young
Lee Jong-Min
Kim Han-Young
Shin Chan-Young
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Abstract
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Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer’s disease (AD), multiple sclerosis (MS), Parkinson’s disease (PD) and stroke.
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KEYWORD
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Coptis japonica, Microglia, Nitric oxide (NO), Inducible nitric oxide synthase (iNOS), Matrixmetalloproteinase-9 (MMP-9)
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