Anti-neuroinflammatory Activity of Nobiletin on Suppression of Microglial Activation

被引：112

作者：

Cui, Yanji ^{[1
,2
]}

Wu, Jinji ^{[1
,2
]}

Jung, Sung-Cherl ^{[1
,2
]}

Park, Deok-Bae ^{[1
,3
]}

Maeng, Young-Hee ^{[1
,4
]}

Hong, Jeong Yun ^{[1
,5
]}

Kim, Se-Jae ^{[6
]}

Lee, Sun-Ryung ^{[6
]}

Kim, Soon-Jong ^{[7
]}

Kim, Sang Jeong ^{[8
]}

Eun, Su-Yong ^{[1
,2
]}

机构：

[1] Jeju Natl Univ, Sch Med, Inst Med Sci, Jeju Si 690756, Jeju Do, South Korea

[2] Jeju Natl Univ, Sch Med, Dept Physiol, Jeju Si 690756, Jeju Do, South Korea

[3] Jeju Natl Univ, Sch Med, Dept Histol, Jeju Si 690756, Jeju Do, South Korea

[4] Jeju Natl Univ, Sch Med, Dept Pathol, Jeju Si 690756, Jeju Do, South Korea

[5] Jeju Natl Univ, Sch Med, Dept Pediat, Jeju Si 690756, Jeju Do, South Korea

[6] Jeju Natl Univ, Dept Biol, Jeju Si 690756, Jeju Do, South Korea

[7] Mokpo Natl Univ, Dept Chem, Muan Gun 534729, Chonnam, South Korea

[8] Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul 110799, South Korea

来源：

BIOLOGICAL & PHARMACEUTICAL BULLETIN | 2010年 / 33卷 / 11期

关键词：

nobiletin; microglia; neuroinflammation; nuclear factor kappa B; neurodegeneration; citrus; PROTEIN-KINASE-C; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; IMPROVES MEMORY IMPAIRMENT; CHRONIC BRAIN INFLAMMATION; FOCAL CEREBRAL-ISCHEMIA; NF-KAPPA-B; ALZHEIMERS-DISEASE; CELL-DEATH; MINOCYCLINE; GLUTAMATE;

D O I：

10.1248/bpb.33.1814

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 NH2-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.

引用

页码：1814 / 1821

页数：8