Bergamottin alleviates LPS-induced acute lung injury by inducing SIRT1 and suppressing NF-κB.

Abstract

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.

• Authors: Ning An, Tao Yang, Xiao-Xia Zhang, Mei-Xia Xu
• Journal: Innate immunity (Innate Immun) Vol. 27 Issue 7-8 Pg. 543-552 (10 2021) ISSN: 1753-4267 [Electronic] United States
• PMID: 34812690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Furocoumarins
• Lipopolysaccharides
• NF-kappa B
• Sirt1 protein, mouse
• Sirtuin 1
• bergamottin

Topics

• Acute Lung Injury (chemically induced, drug therapy, metabolism)
• Animals
• Bronchoalveolar Lavage Fluid
• Cytokines (metabolism)
• Furocoumarins (adverse effects)
• Lipopolysaccharides (pharmacology)
• Lung
• Mice
• NF-kappa B (metabolism)
• Sirtuin 1