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Total ginsenosides increase coronary perfusion flow in isolated rat hearts through activation of PI3K/Akt-eNOS signaling.

AbstractBACKGROUND:
Ginseng is the most popular herb used for treatment of ischemic heart diseases in Chinese community; ginsenosides are considered to be the major active ingredients. However, whether ginsenosides can enhance the coronary artery flow of ischemic heart and, if so, by what mechanisms they do this, remains unclear.
METHODS:
Isolated rat hearts with ischemia/reperfusion injury in Langendorff system were employed for examining the effect of total ginsenosides (TGS) on coronary perfusion flow (CPF). In addition, human aortic endothelial cells (HAECs) were used for mechanistic study. Levels of various vasodilative molecules, intracellular calcium concentration ([Ca²+](i)), and expressions and activation of proteins involving regulation of nitric oxide (NO) signaling pathways in heart tissues and HAECs were determined.
RESULTS:
TGS dose-dependently and significantly increased CPF and improved systolic and diastolic function of the ischemia/reperfused rat heart, while inhibitors of NO synthase (NOS), soluble guanylate cyclase (sGC), heme oxygenase (HO), cyclooxygenase (COX), and potassium channel abolished the vasodilation effect of TGS. Positive control verapamil was effective only in increasing CPF. TGS elevated levels of NO and 6-keto-prostaglandin F₁α, a stable hydrolytic product of prostacyclin I₂ (PGI₂), in both coronary effluents and supernatants of HAECs culturing medium, and augmented [Ca²+](i) in HAECs. TGS significantly up-regulated expression of phosphoinositide 3-kinase (PI3K) and phosphorylations of Akt and endothelial NOS (eNOS) as well.
CONCLUSIONS:
TGS significantly increased CPF of ischemia/reperfused rat hearts through elevation of NO production via activation of PI3K/Akt-eNOS signaling. In addition, PGI₂, EDHF and CO pathways also partially participated in vasodilation induced by TGS.
AuthorsXiao Qin Yi, Ting Li, Jing Rong Wang, Vincent Kam Wai Wong, Pei Luo, Ivan Yuen Fan Wong, Zhi Hong Jiang, Liang Liu, Hua Zhou
JournalPhytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 17 Issue 13 Pg. 1006-15 (Nov 2010) ISSN: 1618-095X [Electronic] Germany
PMID20724124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier GmbH. All rights reserved.
Chemical References
  • Enzyme Inhibitors
  • Ginsenosides
  • Plant Extracts
  • Vasodilator Agents
  • Nitric Oxide
  • Verapamil
  • Nitric Oxide Synthase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
Topics
  • Animals
  • Coronary Circulation (drug effects)
  • Coronary Vessels (drug effects, physiopathology)
  • Dose-Response Relationship, Drug
  • Endothelial Cells (drug effects)
  • Endothelium, Vascular (cytology, drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Ginsenosides (pharmacology, therapeutic use)
  • Heart (drug effects, physiopathology)
  • Male
  • Myocardial Ischemia (drug therapy, metabolism, physiopathology)
  • Myocardial Reperfusion Injury (physiopathology, prevention & control)
  • Nitric Oxide (metabolism)
  • Nitric Oxide Synthase (metabolism)
  • Panax (chemistry)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts (pharmacology, therapeutic use)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction (drug effects)
  • Vasodilator Agents (pharmacology, therapeutic use)
  • Verapamil (pharmacology)

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