Acute lung injury (ALI) is associated with a high mortality due to inflammatory cell infiltration and lung edema. The development of ALI commonly involves the activation of NF-κB. Since bergamottin is a natural furanocoumarin showing the ability to inhibit the activation of NF-κB, in this study we aimed to determine the effect of bergamottin on ALI. RAW264.7 mouse macrophages were pre-treated with bergamottin and then stimulated with LPS. Macrophage inflammatory responses were examined. Bergamottin (50 mg/kg body mass) was intraperitoneally administrated to mice 12 h before injection of LPS, and the effect of bergamottin on LPS-induced ALI was evaluated. Our results showed that LPS exposure led to increased production of TNF-α, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which was impaired by bergamottin pre-treatment. In vivo studies confirmed that bergamottin pre-treatment suppressed LPS-induced lung inflammation and edema and reduced the levels of pro-inflammatory cytokines in lung tissues and bronchoalveolar lavage fluids. Mechanistically, bergamottin blocked LPS-induced activation of NF-κB signaling in lung tissues. Additionally, bergamottin treatment reduced NF-κB p65 protein acetylation, which was coupled with induction of SIRT1 expression. In conclusion, our results reveal the anti-inflammatory property of bergamottin in preventing ALI. Induction of SIRT1 and inhibition of NF-κB underlies the anti-inflammatory activity of bergamottin.

由于炎症细胞浸润和肺水肿，急性肺损伤 (ALI) 与高死亡率相关。ALI的发展通常涉及NF-κB的激活。由于佛手柑是一种天然呋喃香豆素，具有抑制 NF-κB 活化的能力，因此在本研究中，我们旨在确定佛手柑对 ALI 的影响。RAW264.7 小鼠巨噬细胞用佛手柑预处理，然后用 LPS 刺激。检查巨噬细胞炎症反应。在注射 LPS 前 12 小时，将佛手柑（50 mg/kg 体重）腹膜内给予小鼠，并评估佛手柑对 LPS 诱导的 ALI 的影响。我们的研究结果表明，LPS 暴露导致 TNF-α、IL-6 和单核细胞趋化蛋白 1 (MCP-1) 的产生增加，而佛手柑预处理会损害这些产生。体内研究证实，佛手柑预处理可抑制 LPS 诱导的肺部炎症和水肿，并降低肺组织和支气管肺泡灌洗液中促炎细胞因子的水平。从机制上讲，佛手柑阻断了 LPS 诱导的肺组织中 NF-κB 信号的激活。此外，佛手柑处理降低了 NF-κB p65 蛋白乙酰化，这与 SIRT1 表达的诱导相结合。总之，我们的结果揭示了佛手柑在预防 ALI 中的抗炎特性。SIRT1 的诱导和 NF-κB 的抑制是佛手柑抗炎活性的基础。