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Hesperetin Suppresses Inflammatory Responses in Lipopolysaccharide-Induced RAW 264.7 Cells via the Inhibition of NF-κB and Activation of Nrf2/HO-1 Pathways

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Abstract

Hesperetin (Hesp), a common flavanone glycoside, was extracted from the fruit peel of Citrus aurantium L. (Rutaceae). Hesp has been shown to possess various biological properties, including antioxidant, neuroprotective, and anti-inflammatory properties. In this study, we investigated the protective effect of Hesp on inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our results indicated that Hesp treatment dramatically suppressed secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β; reduced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expression; inhibited NF-κB (p65) phosphorylation; and blocked IκBα phosphorylation and degradation. Further studies revealed Hesp markedly enhanced the heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, which were involved with inducing Nrf2 nuclear translocation and decreasing Keap1 protein expression. Together, these results indicated that the anti-inflammatory effect of Hesp may be associated with NF-κB inhibition and Nrf2/HO-1 activation.

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Acknowledgments

This work supported by a grant from the Natural Science Foundation of Jilin (no. 20150520050JH).

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    Authors and Affiliations

    1. Department of Ophthalmology, First Hospital of Jilin University, Changchun, 130021, China

      Hua Ren, Jilong Hao, Taotao Liu, Dongyan Zhang, Hongming Lv & E. Song

    2. Department of Ophthalmology, Second Hospital of Jilin University, Changchun, 130021, China

      Chao Zhu

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    1. Hua Ren
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    2. Jilong Hao
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    Correspondence to E. Song or Chao Zhu.

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    Hua Ren and Jilong Hao contributed equally to this work.

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    Ren, H., Hao, J., Liu, T. et al. Hesperetin Suppresses Inflammatory Responses in Lipopolysaccharide-Induced RAW 264.7 Cells via the Inhibition of NF-κB and Activation of Nrf2/HO-1 Pathways. Inflammation 39, 964–973 (2016). https://doi.org/10.1007/s10753-016-0311-9

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    • DOI: https://doi.org/10.1007/s10753-016-0311-9

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