title: Dioscin attenuates gastric ischemia/reperfusion injury through the down-regulation of PKC/ERK1/2 signaling via PKCα and PKCβ2 inhibition.
abstract: BACKGROUND
  We previously reported the promising effects of dioscin against cerebral and renal ischemia-reperfusion (I/R) injury. However, its role against gastric I/R injury has not yet been reported. Thus, the aim of the present work was to investigate the protective effect and possible mechanisms of dioscin against gastric I/R.
  
  
  METHODS
  The hypoxia-reoxygenation (H/R) model in GES-1 cells and the celiac artery occlusion model in rats were carried out in the study.
  
  
  RESULTS
  Dioscin markedly attenuated H/R insult in GES-1 cells and gastric I/R injury in rats. Mechanistic studies demonstrated that dioscin-induced gastric protection was accompanied by inhibiting the levels of PKCα, PKCβ2 and phosphorylation via decreasing Raf-1 level. Blockade of PKC/ERK1/2 signaling pathway by dioscin decreased MEK1/2 level, ERK1/2 phosphorylation and the nuclear translocation, NF-κB and AP-1 transcriptional activities, pro-inflammatory cytokine responses, and up-regulated PPAR-γ level. Moreover, the results of small interfering RNA (siRNA) and overexpression of PKCα and PKCβ2 confirmed that dioscin attenuated gastric I/R injury through inhibiting PKC/ERK1/2 signaling by down-regulating PKCα and PKCβ2.
  
  
  CONCLUSIONS
  These data confirmed the protective effect of dioscin against gastric I/R injury, which should be developed as a therapeutic agent for the treatment of acute gastric mucosal lesions in the future.
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Hu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Tao
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Electronic address: jinyongpeng2008@126.com.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D064546:Protein Kinase C beta / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013270:Stomach / Q000098:blood supply / Q000473:pathology
chemical_list: D007527:Isoenzymes; D020011:Protective Agents; C019357:dioscin; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D004144:Diosgenin
keywords: Anti-oxidative stress; Dioscin; Gastric ischemia-reperfusion; Natural product; PKC/ERK1/2 signaling pathway