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

Autor: Ting Li, Pei Luo, Zhi-Hong Jiang, Jing-Rong Wang, Ivan Yuen Fan Wong, Liang Liu, Xiao Qin Yi, Vincent Kam Wai Wong, Hua Zhou
Rok vydání: 2010
Předmět:
Male
Ginsenosides
Vasodilator Agents
Myocardial Ischemia
Pharmaceutical Science
Prostacyclin
Vasodilation
Pharmacology
Rats
Sprague-Dawley
chemistry.chemical_compound
Phosphatidylinositol 3-Kinases
Enos
Drug Discovery
Enzyme Inhibitors
Phosphorylation
biology
Heart
Coronary Vessels
Nitric oxide synthase
medicine.anatomical_structure
Biochemistry
cardiovascular system
Molecular Medicine
lipids (amino acids
peptides
and proteins)
medicine.drug
Signal Transduction
Endothelium
Panax
Myocardial Reperfusion Injury
Endothelial NOS
Nitric Oxide
Nitric oxide
Coronary Circulation
medicine
Animals
Dose-Response Relationship
Drug
business.industry
Plant Extracts
Endothelial Cells
medicine.disease
biology.organism_classification
Rats
Complementary and alternative medicine
chemistry
Verapamil
biology.protein
Endothelium
Vascular
Nitric Oxide Synthase
business
Reperfusion injury
Proto-Oncogene Proteins c-akt
Phytotherapy
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology. 17(13)
ISSN: 1618-095X
Popis: Background 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.
Databáze: OpenAIRE
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