title: Protective effects of icariin-mediated SIRT1/FOXO3 signaling pathway on intestinal ischemia/reperfusion-induced acute lung injury.
abstract: Acute lung injury (ALI) is a common complication following intestinal ischemia/reperfusion (I/R) and is a major contributing factor to its high mortality rate. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, has been reported to have an important role in apoptosis inhibition, oxidative stress resistance and cell lifespan extension through its deacetylation of forkhead box protein O3 (FOXO3). It has been demonstrated that icariin (ICA), a flavonoid extracted from Epimedium, upregulates SIRT1 expression. The aim of the present study was to examine whether ICA-mediated SIRT1/FOXO3 signaling pathway activation had a protective effect on intestinal I/R-induced ALI. The effects of ICA on intestinal I/R-induced ALI and its regulation of the SIRT1/FOXO3 signaling pathway on intestinal I/R-induced ALI were investigated in rats. The results demonstrated that ICA pretreatment markedly reduced intestinal I/R-induced ALI as indicated by histological alterations, including decreased tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), reduced oxidative stress, acetylated FOXO3 and B-cell lymphoma 2 (Bcl-2)-interacting mediator of cell death levels, and increased glutathione (GSH), GSH peroxidase, SIRT1, manganese superoxide dismutase and Bcl-2 levels in rat lung tissues. Furthermore, ICA pretreatment upregulated SIRT1 expression, which then downregulated FOXO3 acetylation. In conclusion, ICA exhibited significant protective effects in intestinal I/R-induced ALI. The protective effect of ICA may be attributed to the upregulation of SIRT1, which contributed to FOXO3 deacetylation and the modulation of downstream antioxidative and anti-apoptotic factors.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Zhen-Lu
authors.initials: ZL
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Yao
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Hui-Rong
authors.initials: HR
authors.lastname: Jing
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Shi-Li
authors.initials: SL
authors.lastname: Ning
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tian
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications*; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D016207:Cytokines; C499515:FOXO3 protein, rat; D005419:Flavonoids; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D056564:Sirtuin 1; D005978:Glutathione; C056599:icariin