Inhibition of gene expression and production of iNOS and TNF-alpha in LPS-stimulated microglia by methanol extract of Phellodendri cortex.
Activation of microglia has been increasingly associated with the pathogenesis of several neurodegenerative disorders including Parkinson's and Alzheimer's diseases, and the suppression of microglial activation may lead to alleviation of the progression of neurodegeneration in these diseases. We sought to investigate whether Phellodendri cortex (PC) that has been used for centuries in Chinese traditional medicine for the treatment of various inflammatory conditions, inhibits production of anti-inflammatory cytokines and nitric oxide (NO) in microglia, and further studied the molecular and cellular mechanisms that govern these anti-inflammatory effects. The methanol extract of PC (PC extract) attenuated LPS-stimulated increase in production of TNF-alpha, IL-1beta, and NO in BV2 cells, a mouse microglia cell line, as well as in primary mouse microglia. The RNase protection assay and RT-PCR revealed that the PC extracts inhibited increases in mRNAs of these cytokines and iNOS in LPS-stimulated BV2 cells. The PC extracts significantly decreased release of these cytokines and NO from LPS-stimulated microglia in a dose-dependent manner. Molecular mechanisms that govern attenuation of the levels of mRNAs and proteins of these cytokines and iNOS revealed that the PC extract inhibited LPS-stimulated phosphorylation of ERK and activation of NF-kappaB. The studies demonstrate that the PC extract effectively inhibits microglial production and release of inflammatory cytokines and NO, and could be a candidate agent for anti-inflammation in neurodegenerative human brain diseases.
Park
Yong-Ki
YK
Burke Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 785 Mamaroneck Avenue, White Plains, NY, USA.
Chung
Yoo Sun
YS
Kim
Yoon Seong
YS
Kwon
O-Yoon
OY
Joh
Tong H
TH
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D007155:Immunologic Factors / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D000432:Methanol / Q000737:chemistry; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000187:drug effects; D032102:Phellodendron / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects
D007155:Immunologic Factors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D000432:Methanol