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Nobiletin-Ameliorated Lipopolysaccharide-Induced Inflammation in Acute Lung Injury by Suppression of NF-κB Pathway In Vivo and Vitro

  • Weifeng Li
  • Ruoqi Zhao
  • Xiumei Wang
  • Fang Liu
  • Jinmeng Zhao
  • Qing Yao
  • Wenbing Zhi
  • Zehong He
  • Xiaofeng Niu


Nobiletin (NOB), a citrus polymethoxy flavonoid, has been reported to exhibit anti-inflammatory, anti-cancer, and anti-insulin resistance activities. Although the anti-inflammatory activity of NOB already reported, its involvement in lung protection has not been reported. Thus, this study aimed to investigate the anti-inflammatory response of NOB in lipopolysaccharide (LPS)-stimulated A549 cells and LPS-induced acute lung injury (ALI) in mice. The animals were pre-treated with NOB (5, 10, and 20 mg/kg) or DEX (5 mg/kg) at 12 and 1 h before intranasal instillation of LPS. The severity of pulmonary injury was evaluated 6 h after LPS administration. Results suggested that treatment with NOB dramatically attenuated lung histopathological changes, wet-to-dry (W/D) ratio, myeloperoxidase (MPO) activity, the numbers of inflammatory cells, and TNF-α, IL-6, and NO in BALF induced by LPS. Furthermore, NOB also significantly inhibited the expression of iNOS and the phosphorylation of NF-κBp65 and IκBα. In vitro, NOB inhibited NF-κB activation and TNF-α, IL-6 production in LPS-stimulated A549 cells. Taken together, these results indicated that NOB exhibited a protective effect on ALI, and the possible mechanism is involved in inhibiting NF-κB activation, subsequently inhibiting LPS-induced inflammatory response.


nobiletin acute lung injury LPS NF-κB inflammation 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Weifeng Li
    • 1
  • Ruoqi Zhao
    • 2
  • Xiumei Wang
    • 1
  • Fang Liu
    • 1
  • Jinmeng Zhao
    • 1
  • Qing Yao
    • 1
  • Wenbing Zhi
    • 1
  • Zehong He
    • 1
  • Xiaofeng Niu
    • 1
  1. 1.School of PharmacyXi’an Jiaotong UniversityXi’an CityPeople’s Republic of China
  2. 2.Queen Mary CollegeNanchang UniversityNanchangPeople’s Republic of China

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