Nobiletin attenuates lipopolysaccharide/D‑galactosamine‑induced liver injury in mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF‑κB‑mediated cytokine production

  • Authors:
    • Zhenxing He
    • Xuanfei Li
    • Hao Chen
    • Kun He
    • Yiming Liu
    • Junhua Gong
    • Jianping Gong
  • View Affiliations

  • Published online on: November 15, 2016     https://doi.org/10.3892/mmr.2016.5943
  • Pages: 5595-5600
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Abstract

Inflammation and oxidative stress serve an important role in the development of lipopolysaccharide/D-galactosamine (LPS/GalN)‑induced acute liver injury. Nobiletin, which is found in high quantities in the peel of citrus fruits, is able to modulate immune responses, including inflammatory response and oxidative stress. The present study aimed to evaluate the protective effects of nobiletin on LPS/GalN‑induced acute liver injury. Male C57BL/6 mice were intraperitoneally treated with nobiletin (50, 100 and 200 mg/kg) 2 h prior to LPS/GalN injection. Liver injury was observed in the LPS/GalN group, as demonstrated by increased levels of serum hepatic enzymes and hepatic inflammatory mediators, as well as by histopathological alterations. Treatment with nobiletin reduced serum alanine aminotransferase and aspartate aminotransferase levels, improved hepatic structure, and suppressed hepatic interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α production 24 h after LPS/GalN exposure. Western blot analysis revealed that nobiletin treatment inhibited inducible nitric oxide synthase and cyclooxygenase‑2 liver expression. In addition, nobiletin suppressed LPS/GalN‑induced phosphorylation and degradation of inhibitor of nuclear factor (NF)‑κB (IκB)α, as well as NF‑κB p65 translocation into the nucleus. Nobiletin also upregulated the expression of nuclear NF‑E2‑related factor 2 (Nrf2) and cytoplasmic heme oxygenase‑1. In conclusion, these results indicate that nobiletin serves a protective role in LPS/GalN‑induced acute liver injury via activation of the Nrf2 antioxidant pathway and subsequent inhibition of NF‑κB‑mediated cytokine production. These findings support the potential for nobiletin as a therapeutic agent for the treatment of acute liver injury.
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December-2016
Volume 14 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
He Z, Li X, Chen H, He K, Liu Y, Gong J and Gong J: Nobiletin attenuates lipopolysaccharide/D‑galactosamine‑induced liver injury in mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF‑κB‑mediated cytokine production. Mol Med Rep 14: 5595-5600, 2016
APA
He, Z., Li, X., Chen, H., He, K., Liu, Y., Gong, J., & Gong, J. (2016). Nobiletin attenuates lipopolysaccharide/D‑galactosamine‑induced liver injury in mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF‑κB‑mediated cytokine production. Molecular Medicine Reports, 14, 5595-5600. https://doi.org/10.3892/mmr.2016.5943
MLA
He, Z., Li, X., Chen, H., He, K., Liu, Y., Gong, J., Gong, J."Nobiletin attenuates lipopolysaccharide/D‑galactosamine‑induced liver injury in mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF‑κB‑mediated cytokine production". Molecular Medicine Reports 14.6 (2016): 5595-5600.
Chicago
He, Z., Li, X., Chen, H., He, K., Liu, Y., Gong, J., Gong, J."Nobiletin attenuates lipopolysaccharide/D‑galactosamine‑induced liver injury in mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF‑κB‑mediated cytokine production". Molecular Medicine Reports 14, no. 6 (2016): 5595-5600. https://doi.org/10.3892/mmr.2016.5943