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

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Abstract

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.

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Funding

This work was supported by a research grant (no.: 2013KW26-02) from the Natural Science Foundation of International Cooperation Projects (Shaanxi Province, PR China).

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Authors and Affiliations

  1. School of Pharmacy, Xi’an Jiaotong University, No. 76 Western Yanta Road, Xi’an City, 710061, Shaanxi Province, People’s Republic of China

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

  2. Queen Mary College, Nanchang University, Nanchang, 330019, People’s Republic of China

    Ruoqi Zhao

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  1. Weifeng Li
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Correspondence to Xiaofeng Niu.

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Li, W., Zhao, R., Wang, X. et al. Nobiletin-Ameliorated Lipopolysaccharide-Induced Inflammation in Acute Lung Injury by Suppression of NF-κB Pathway In Vivo and Vitro. Inflammation 41, 996–1007 (2018). https://doi.org/10.1007/s10753-018-0753-3

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