Linked Life Data

12473078

Source:http://linkedlifedata.com/resource/pubmed/id/12473078

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-12-10
pubmed:abstractText
An inflammatory response in the central nervous system mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Silymarin is a polyphenolic flavanoid derived from milk thistle that has anti-inflammatory, cytoprotective and anticarcinogenic effects. In this study, we first investigated the neuroprotective effect of silymarin against lipopolysaccharide (LPS)-induced neurotoxicity in mesencephalic mixed neuron-glia cultures. The results showed that silymarin significantly inhibited the LPS-induced activation of microglia and the production of inflammatory mediators, such as tumour necrosis factor-alpha and nitric oxide (NO), and reduced the damage to dopaminergic neurons. Therefore, the inhibitory mechanisms of silymarin on microglia activation were studied further. The production of inducible nitric oxide synthase (iNOS) was studied in LPS-stimulated BV-2 cells as a model of microglia activation. Silymarin significantly reduced the LPS-induced nitrite, iNOS mRNA and protein levels in a dose-dependent manner. Moreover, LPS could induce the activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase but not extracellular signal-regulated kinase. The LPS-induced production of NO was inhibited by the selective p38 MAPK inhibitor SB203580. These results indicated that the p38 MAPK signalling pathway was involved in the LPS-induced NO production. However, the activation of p38 MAPK was not inhibited by silymarin. Nevertheless, silymarin could effectively reduce LPS-induced superoxide generation and nuclear factor kappaB (NF-kappaB) activation. It suggests that the inhibitory effect of silymarin on microglia activation is mediated through the inhibition of NF-kappaB activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2103-12
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12473078-Animals, pubmed-meshheading:12473078-Cells, Cultured, pubmed-meshheading:12473078-Coculture Techniques, pubmed-meshheading:12473078-Dopamine, pubmed-meshheading:12473078-Dose-Response Relationship, Drug, pubmed-meshheading:12473078-Encephalitis, pubmed-meshheading:12473078-Fetus, pubmed-meshheading:12473078-Gliosis, pubmed-meshheading:12473078-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:12473078-Lipopolysaccharides, pubmed-meshheading:12473078-Mesencephalon, pubmed-meshheading:12473078-Microglia, pubmed-meshheading:12473078-Mitogen-Activated Protein Kinases, pubmed-meshheading:12473078-NF-kappa B, pubmed-meshheading:12473078-Neurodegenerative Diseases, pubmed-meshheading:12473078-Neurons, pubmed-meshheading:12473078-Neurotoxins, pubmed-meshheading:12473078-Protective Agents, pubmed-meshheading:12473078-RNA, Messenger, pubmed-meshheading:12473078-Rats, pubmed-meshheading:12473078-Rats, Inbred F344, pubmed-meshheading:12473078-Silymarin, pubmed-meshheading:12473078-p38 Mitogen-Activated Protein Kinases
pubmed:year
2002
pubmed:articleTitle
Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation.
pubmed:affiliation
Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't