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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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