PMID- 34812690 OWN - NLM STAT- MEDLINE DCOM- 20220316 LR - 20220316 IS - 1753-4267 (Electronic) IS - 1753-4259 (Print) IS - 1753-4259 (Linking) VI - 27 IP - 7-8 DP - 2021 Oct TI - Bergamottin alleviates LPS-induced acute lung injury by inducing SIRT1 and suppressing NF-kappaB. PG - 543-552 LID - 10.1177/17534259211062553 [doi] AB - 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-kappaB. Since bergamottin is a natural furanocoumarin showing the ability to inhibit the activation of NF-kappaB, 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-alpha, 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-kappaB signaling in lung tissues. Additionally, bergamottin treatment reduced NF-kappaB 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-kappaB underlies the anti-inflammatory activity of bergamottin. FAU - An, Ning AU - An N AD - Institue of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China. FAU - Yang, Tao AU - Yang T AD - Department of Intensive Care Unit, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Xiao-Xia AU - Zhang XX AD - Department of Intensive Care Unit, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China. FAU - Xu, Mei-Xia AU - Xu MX AUID- ORCID: 0000-0003-2667-1577 AD - Department of Intensive Care Unit, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211123 PL - United States TA - Innate Immun JT - Innate immunity JID - 101469670 RN - 0 (Cytokines) RN - 0 (Furocoumarins) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - EC 3.5.1.- (Sirt1 protein, mouse) RN - EC 3.5.1.- (Sirtuin 1) RN - JMU611YFRB (bergamottin) SB - IM MH - *Acute Lung Injury/chemically induced/drug therapy/metabolism MH - Animals MH - Bronchoalveolar Lavage Fluid MH - Cytokines/metabolism MH - *Furocoumarins/adverse effects MH - Lipopolysaccharides/pharmacology MH - Lung MH - Mice MH - NF-kappa B/metabolism MH - Sirtuin 1 PMC - PMC8762093 OTO - NOTNLM OT - Acetylation OT - NF-kappaB OT - SIRT1 OT - bergamottin OT - lung inflammation COIS- Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2021/11/24 06:00 MHDA- 2022/03/17 06:00 PMCR- 2021/11/23 CRDT- 2021/11/23 12:15 PHST- 2021/11/24 06:00 [pubmed] PHST- 2022/03/17 06:00 [medline] PHST- 2021/11/23 12:15 [entrez] PHST- 2021/11/23 00:00 [pmc-release] AID - 10.1177_17534259211062553 [pii] AID - 10.1177/17534259211062553 [doi] PST - ppublish SO - Innate Immun. 2021 Oct;27(7-8):543-552. doi: 10.1177/17534259211062553. Epub 2021 Nov 23.