title: Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway.
abstract: OBJECTIVE
  Compound K (C-K; 20-O-D-glucopyranosyl-20(S)-protopanaxadiol) is a novel ginsenoside metabolite formed by intestinal bacteria and does not occur naturally in ginseng. In this study, we investigated whether administration of C-K has protective effects on myocardial ischemia-reperfusion injury and its potential mechanisms.
  
  
  METHODS
  We used in vivo mouse models of ischemia-reperfusion injury and performed biochemical assays in excised hearts.
  
  
  RESULTS
  C-K reduced infarct size compared with the control group after ischemia-reperfusion. Immunoblot analysis showed that C-K significantly enhanced protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) activity. Wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked cardiac protection in vivo and attenuated phosphorylation of Akt and eNOS. Additionally, the hearts of C-K pretreated mice showed inhibition of mitochondrial swelling induced by Ca(2+).
  
  
  CONCLUSIONS
  This study showed that Compound K pretreatment has protective effects on myocardial ischemia-reperfusion injury, partly by mediating the activation of PI3K pathway and phosphorylation of Akt and eNOS.
authors.affiliation: Department of Anesthesiology, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan. tsutsumi@clin.med.tokushima-u.ac.jp
authors.forename: Yasuo M
authors.initials: YM
authors.lastname: Tsutsumi
authors.forename: Rie
authors.initials: R
authors.lastname: Tsutsumi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Michiko
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shuzo
authors.initials: S
authors.lastname: Oshita
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000378:metabolism; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy*; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002118:Calcium; D036145:Ginsenosides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; C112772:ginsenoside compound K