Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysaccharide-stimulated microglial cells.
Increasing evidence suggests that tangeretin, a flavonoid from citrus fruit peels, exhibits anti-inflammatory properties and neuroprotective effects in animal disease models. However, the underlying molecular mechanisms are not clearly understood. In this study, we investigated whether tangeretin suppresses excessive microglial activation implicated in the resulting neurotoxicity following stimulation with lipopolysaccharide (LPS) in primary rat microglia and BV-2 microglial cell culture models. The results showed that tangeretin decreased the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), in a dose-dependent manner. Additionally, it inhibited the LPS-induced expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (examined at the protein level) as well as TNF-α, IL-1β, and IL-6 (examined at the mRNA level) in microglial cells. To explore the possible mechanisms underlying these inhibitions by tangeretin, we examined the mitogen-activated protein kinase (MAPK) protein levels and the NF-κB protein signaling pathway. Tangeretin clearly inhibited LPS-induced phosphorylation of ERK, N-terminal Kinase (JNK), and p38. In addition, tangeretin markedly reduced LPS-stimulated phosphorylation of IκB-α and IKK-β, as well as the nuclear translocation of the p65 subunit of pro-inflammatory transcription factor NF-κB. Taken together, these results support further exploration of the therapeutic potential and molecular mechanism of tangeretin in relation to neuroinflammation and neurodegenerative diseases accompanied by microglial activation.
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
Zunpeng
Z
Shu
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
Bingyou
B
Yang
Pharmacy College of Jiamusi University, Jiamusi 154002, China; Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
Hong
H
Zhao
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
Bingqing
B
Xu
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
Wenjuan
W
Jiao
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
Qiuhong
Q
Wang
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.
Zhibin
Z
Wang
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China. Electronic address: hxkuang@hotmail.com.
Haixue
H
Kuang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000893:Anti-Inflammatory Agents; D047309:Flavones; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; C059006:tangeretin; D015232:Dinoprostone
Anti-neuroinflammation; BV-2 microglial cells; Nuclear factor-κB; Primary rat microglial cells; Tangeretin