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Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia
- Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia
- Lee, Yu Young; Lee, Eun-Jung; Park, Jin-Sun; Jang, Se-Eun; Kim, Dong-Hyun; Kim, Hee-Sun
- Ewha Authors
- 김희선; 박진선; 이은정
- SCOPUS Author ID
- 김희선; 박진선; 이은정
- Issue Date
- Journal Title
- JOURNAL OF NEUROIMMUNE PHARMACOLOGY
- 1557-1890; 1557-1904
- vol. 11, no. 2, pp. 294 - 305
- Tangeretin; Microglia; Anti-inflammation; Antioxidant; MMP; Molecular mechanism
- SCIE; SCOPUS
- 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-1 beta, 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-kappa B 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.
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