Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia

Yu Young Lee, Eun Jung Lee, Jin Sun Park, Se Eun Jang, Dong Hyun Kim, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


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 p47phox 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.

Original languageEnglish
Pages (from-to)294-305
Number of pages12
JournalJournal of Neuroimmune Pharmacology
Issue number2
StatePublished - 1 Jun 2016

Bibliographical note

Publisher Copyright:
© 2016, Springer Science+Business Media New York.


  • Anti-inflammation
  • Antioxidant
  • MMP
  • Microglia
  • Molecular mechanism
  • Tangeretin


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