Investigation of the inhibitory mechanisms of N-hydroxycinnamoylphenalkylamides analogue on microglia activation and its anti-neuroinflammatory effects in vivo

Autor: Fan-Li Lin, 林凡立
Rok vydání: 2009
Druh dokumentu: 學位論文 ; thesis
Popis: 97
Glial activation and neuroinflammatory processes play an important role in the pathogenesis of neurodegenerative diseases such as post-stroke brain injury, multiple sclerosis, Alzheimer''s disease, Parkinson''s disease, and HIV dementia. Activated glial cells can secrete various proinflammatory cytokines and neurotoxic mediators, which may contribute to neuronal cell death. Inhibition of glial activation may alleviate neurodegeneration under these conditions. The results showed that EK8 (20μM) attenuated the expression of inducible nitric oxide synthase in the lipopolysaccharide-stimulated microglia cells. Moreover, EK8 inhibited IκB degradation, nuclear translocation of the p65 subunit of NF-κB, and phosphorylation of JNK and p38 in mitogen-activated protein kinase (MAPK) signaling. Ex vivo experiment suggested that EK8 inhibited lipid peroxidation and scavenged the free radicals significantly. In addition, EK8 decreased astrocyte hypertrophy and nitrotyrosine formation in LPS-injected brain. Therefore, these results imply that EK8 have anti-inflammatory and neuroprotective effects in the central nervous system by modulating glial activation and anti-oxidation activity.
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