Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway.

Abstract

AIMS:

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.

MAIN METHODS:

We used in vivo mouse models of ischemia-reperfusion injury and performed biochemical assays in excised hearts.

KEY FINDINGS:

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+).

SIGNIFICANCE:

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: Yasuo M Tsutsumi, Rie Tsutsumi, Kazuaki Mawatari, Yutaka Nakaya, Michiko Kinoshita, Katsuya Tanaka, Shuzo Oshita
• Journal: Life sciences (Life Sci) Vol. 88 Issue 15-16 Pg. 725-9 (Apr 11 2011) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 21338613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Androstadienes
• Ginsenosides
• Nitric Oxide
• ginsenoside M1
• Nitric Oxide Synthase Type III
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Calcium
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Animals
• Calcium (metabolism)
• Ginsenosides (pharmacology)
• Immunoblotting
• Male
• Mice
• Mice, Inbred C57BL
• Mitochondria, Heart (metabolism)
• Myocardial Infarction (prevention & control)
• Myocardial Reperfusion Injury (complications, drug therapy)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Wortmannin