NDLI: Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia

Content Provider	Springer Nature Link
Author	Lee, Yu Young Lee, Eun Jung Park, Jin Sun Jang, Se Eun Kim, Dong Hyun Kim, Hee Sun
Copyright Year	2016
Abstract	Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, but further study is necessary for elucidating the detailed mechanisms of these effects. In this study, we examined the anti-inflammatory effect of tangeretin in lipopolysaccharide (LPS)-stimulated microglia. We first observed that tangeretin inhibited LPS-induced production of nitric oxide, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, as well as LPS-induced mRNA expression of inducible nitric oxide synthases and cytokines. Additionally, we found that the activities, mRNA levels, and protein levels of matrix metalloproteinase (MMP)-3 and MMP-8 were inhibited, while the expression of tissue inhibitor of metalloproteinase-2 was enhanced by tangeretin in LPS-stimulated microglia. Further mechanistic study showed that tangeretin suppressed LPS-induced phosphorylation of mitogen-activated protein kinases and Akt. Also, tangeretin inhibited nuclear factor-κB by upregulating sirtuin 1 and 5′-adenosine monophosphate-activated protein kinase. We further demonstrated the antioxidant effect of tangeretin by showing that tangeretin inhibited reactive oxygen species production and p47$^{phox}$ phosphorylation, while enhancing the expression of heme oxygenase-1 and the DNA binding activity of nuclear factor-erythroid 2-related factor 2 to the antioxidant response element in LPS-stimulated microglia. Taken together, the results of the present study demonstrate that tangeretin possesses a potent anti-inflammatory and antioxidant effect in microglia.
Starting Page	294
Ending Page	305
Page Count	12
File Format	PDF
ISSN	15571890
Journal	Journal of Neuroimmune Pharmacology
Volume Number	11
Issue Number	2
e-ISSN	15571904
Language	English
Publisher	Springer US
Publisher Date	2016-02-22
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Tangeretin Microglia Anti-inflammation Antioxidant MMP Molecular mechanism Neurosciences Immunology Pharmacology/Toxicology Virology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Allergy Pharmacology Immunology

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