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Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia

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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 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.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (Grant No. NRF-2010-0027945 and NRF-2015R1A2A2A01005226).

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Authors and Affiliations

  1. Department of Molecular Medicine and Tissue Injury Defense Research Center, Ewha Womans University Medical School, Mok-6-dong 911-1, Yangchun-Ku, Seoul, 158-710, South Korea

    Yu Young Lee, Eun-Jung Lee, Jin-Sun Park & Hee-Sun Kim

  2. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea

    Se-Eun Jang & Dong-Hyun Kim

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  1. Yu Young Lee
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  2. Eun-Jung Lee
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Correspondence to Hee-Sun Kim.

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Lee, Y.Y., Lee, EJ., Park, JS. et al. Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia. J Neuroimmune Pharmacol 11, 294–305 (2016). https://doi.org/10.1007/s11481-016-9657-x

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  • DOI: https://doi.org/10.1007/s11481-016-9657-x

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