TY - JOUR
T1 - Total ginsenosides increase coronary perfusion flow in isolated rat hearts through activation of PI3K/Akt-eNOS signaling
AU - Yi, Xiao Qin
AU - Li, Ting
AU - Wang, Jing Rong
AU - Wong, Vincent Kam Wai
AU - Luo, Pei
AU - Wong, Ivan Yuen Fan
AU - Jiang, Zhi Hong
AU - Liu, Liang
AU - Zhou, Hua
N1 - Funding Information:
This research was funded by the Innovative Technology Fund of Hong Kong ( GHP/054/05 ) and the Faculty Research Grants of Hong Kong Baptist University ( FRG/06-07/II-32 , FRG/07-08/II-71 ). The authors wish to thank Dr. Martha Dahlen for her English editing to this article and Dr. Shao Zhen Hou and Dr. Bao Zeng to provide technical supports.
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Ginsenosides
KW - Langendorff system
KW - Myocardial ischemia/reperfusion injury
KW - PI3K/Akt-eNOS signaling
KW - Vasodilation
UR - http://www.scopus.com/inward/record.url?scp=77957806497&partnerID=8YFLogxK
U2 - 10.1016/j.phymed.2010.06.012
DO - 10.1016/j.phymed.2010.06.012
M3 - Journal article
C2 - 20724124
AN - SCOPUS:77957806497
SN - 0944-7113
VL - 17
SP - 1006
EP - 1015
JO - Phytomedicine
JF - Phytomedicine
IS - 13
ER -
