Institue of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China.
Department of Intensive Care Unit, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China.
Innate Immun. 2021 Oct;27(7-8):543-552. doi: 10.1177/17534259211062553. Epub 2021 Nov 23.
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. 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.
急性肺损伤（ALI）由于炎症细胞浸润和肺水肿而导致死亡率高。ALI 的发展通常涉及 NF-κB 的激活。由于佛手柑素是一种天然呋喃香豆素，具有抑制 NF-κB 激活的能力，因此在本研究中，我们旨在确定佛手柑素对 ALI 的影响。RAW264.7 小鼠巨噬细胞用佛手柑素预处理，然后用 LPS 刺激。检查巨噬细胞炎症反应。在 LPS 注射前 12 小时，腹腔内给予佛手柑素（50mg/kg 体重），并评估佛手柑素对 LPS 诱导的 ALI 的影响。我们的结果表明，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，佛手柑素预处理可损害其产生。进一步的研究证实，佛手柑素预处理抑制了 LPS 诱导的肺炎症和水肿，并降低了肺组织和支气管肺泡灌洗液中促炎细胞因子的水平。在机制上，佛手柑素阻断了 LPS 诱导的肺组织中 NF-κB 信号的激活。此外，佛手柑素治疗降低了 NF-κB p65 蛋白乙酰化，这与 SIRT1 表达的诱导有关。总之，我们的结果揭示了佛手柑素在预防 ALI 中的抗炎特性。SIRT1 的诱导和 NF-κB 的抑制是佛手柑素抗炎活性的基础。
