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Anti-neuroinflammatory Activity of Nobiletin on Suppression of Microglial Activation

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Authors
Cui, Yanji; Wu, Jinji; Park, Deok-Bae; Jung, Sung-Cherl; Hong, Jeong Yun; Lee, Sun-Ryung; Kim, Sang Jeong; Eun, Su-Yong; Kim, Soon-Jong; Kim, Se-Jae; Maeng, Young-Hee
Issue Date
2010-11
Publisher
PHARMACEUTICAL SOC JAPAN
Citation
BIOLOGICAL & PHARMACEUTICAL BULLETIN; Vol.33 11; 1814-1821
Keywords
nobiletinneuroinflammationneurodegenerationcitrusnuclear factor kappa Bmicroglia
Abstract
A growing body of evidence suggests that nobiletin (5,6,7,8,3`,4`-hexamethoxy flavone) from the peel of citrus fruits, enhances the damaged cognitive function in disease animal models. However, the neuroprotective mechanism has not been clearly elucidated. Since nobiletin has shown anti-inflammatory effects in several tissues, we investigated whether nobiletin suppresses excessive microglial activation implicated in neurotoxicity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cell culture models. Release of nitric oxide (NO), the major inflammatory mediator in microglia, was markedly suppressed in a dose-dependent manner following nobiletin treatment (1-50 mu M) in LPS-stimulated BV-2 microglia cells. The inhibitory effect of nobiletin was similar to that of minocycline, a well-known microglial inactivator. Nobiletin significantly inhibited the release of the pro-inflammatory cytokine tumor necrosis factor (TNF-alpha) and interleukin-1 beta (IL-1 beta). LPS-induced phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) were also significantly inhibited by nobiletin treatment. In addition, nobiletin markedly inhibited the LPS-induced pro-inflammatory transcription factor nuclear factor kappa B (NF-kappa B) signaling pathway by suppressing nuclear NF-kappa B translocation from the cytoplasm and subsequent expression of NF-kappa B in the nucleus. Taken together, these results may contribute to further exploration of the therapeutic potential and molecular mechanism of nobiletin in relation to neuroinflammation and neurodegenerative diseases.
ISSN
0918-6158
Language
English
URI
http://hdl.handle.net/10371/76211
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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