title: Icariin protects against intestinal ischemia-reperfusion injury.
abstract: BACKGROUND
  This study investigated the role of Sirtuin 1 (SIRT1)/forkhead box O3 (FOXO3) pathway, and a possible protective function for Icariin (ICA), in intestinal ischemia-reperfusion (I/R) injury and hypoxia-reoxygenation (H/R) injury.
  
  
  METHODS
  Male Sprague-Dawley rats were pretreated with different doses of ICA (30 and 60 mg/kg) or olive oil as control 1 h before intestinal I/R. Caco-2 cells were pretreated with different concentrations of ICA (25, 50, and 100 μg/mL) and then subjected to H/R-induced injury.
  
  
  RESULTS
  The in vivo results demonstrated that ICA pretreatment significantly improved I/R-induced tissue damage and decreased serum tumor necrosis factor α and interleukin-6 levels. Changes of manganese superoxide dismutase, Bcl-2, and Bim were also reversed by ICA, and apoptosis was reduced. Importantly, the protective effects of ICA were positively associated with SIRT1 activation. Increased SIRT1 expression, as well as decreased acetylated FOXO3 expression, was observed in Caco-2 cells pretreated with ICA. Additionally, the protective effects of ICA were abrogated in the presence of SIRT1 inhibitor nicotinamide. This suggests that ICA exerts a protective effect upon H/R injury through activation of SIRT1/FOXO3 signaling pathway. Accordingly, the SIRT1 activator resveratrol achieved a similar protective effect as ICA on H/R injury, whereas cellular damage resulting from H/R was exacerbated by SIRT1 knockdown and nicotinamide.
  
  
  CONCLUSIONS
  SIRT1, activated by ICA, protects intestinal epithelial cells from I/R injury by inducing FOXO3 deacetylation both in vivo and in vitro These findings suggest that the SIRT1/FOXO3 pathway can be a target for therapeutic approaches intended to minimize injury resulting from intestinal dysfunction.
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Shili
authors.initials: S
authors.lastname: Ning
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China. Electronic address: txfdl@hotmail.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Tian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005419:Flavonoids / Q000627:therapeutic use*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D007422:Intestines / Q000098:blood supply*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; C499515:FOXO3 protein, rat; D005419:Flavonoids; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C056599:icariin
keywords: Apoptosis; FOXO3; Icariin; Intestinal ischemia–reperfusion; Oxidative stress; SIRT1