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Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysaccharide-stimulated microglial cells.
Int Immunopharmacol 2014; 19(2):275-82II

Abstract

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.

Authors+Show Affiliations

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.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.Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China.Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China. Electronic address: hxkuang@hotmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24462494

Citation

Shu, Zunpeng, et al. "Tangeretin Exerts Anti-neuroinflammatory Effects Via NF-κB Modulation in Lipopolysaccharide-stimulated Microglial Cells." International Immunopharmacology, vol. 19, no. 2, 2014, pp. 275-82.
Shu Z, Yang B, Zhao H, et al. Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysaccharide-stimulated microglial cells. Int Immunopharmacol. 2014;19(2):275-82.
Shu, Z., Yang, B., Zhao, H., Xu, B., Jiao, W., Wang, Q., ... Kuang, H. (2014). Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysaccharide-stimulated microglial cells. International Immunopharmacology, 19(2), pp. 275-82. doi:10.1016/j.intimp.2014.01.011.
Shu Z, et al. Tangeretin Exerts Anti-neuroinflammatory Effects Via NF-κB Modulation in Lipopolysaccharide-stimulated Microglial Cells. Int Immunopharmacol. 2014;19(2):275-82. PubMed PMID: 24462494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tangeretin exerts anti-neuroinflammatory effects via NF-κB modulation in lipopolysaccharide-stimulated microglial cells. AU - Shu,Zunpeng, AU - Yang,Bingyou, AU - Zhao,Hong, AU - Xu,Bingqing, AU - Jiao,Wenjuan, AU - Wang,Qiuhong, AU - Wang,Zhibin, AU - Kuang,Haixue, Y1 - 2014/01/21/ PY - 2013/09/13/received PY - 2014/01/08/revised PY - 2014/01/13/accepted PY - 2014/1/28/entrez PY - 2014/1/28/pubmed PY - 2014/11/15/medline KW - Anti-neuroinflammation KW - BV-2 microglial cells KW - Nuclear factor-κB KW - Primary rat microglial cells KW - Tangeretin SP - 275 EP - 82 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 19 IS - 2 N2 - 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. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/24462494/Tangeretin_exerts_anti_neuroinflammatory_effects_via_NF_κB_modulation_in_lipopolysaccharide_stimulated_microglial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(14)00014-9 DB - PRIME DP - Unbound Medicine ER -