PMID- 21515242
OWN - NLM
STAT- MEDLINE
DCOM- 20110805
LR  - 20161125
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 82
IP  - 2
DP  - 2011 Jul 15
TI  - Ginsenoside Rb1 prevents homocysteine-induced endothelial dysfunction via 
      PI3K/Akt activation and PKC inhibition.
PG  - 148-55
LID - 10.1016/j.bcp.2011.04.001 [doi]
AB  - Hyperhomocysteinemia (HHcy), a risk factor for cardiovascular disease, is 
      associated with endothelial dysfunction. Ginsenoside Rb1, the major active 
      constituent of ginseng, potently attenuates homocysteine (Hcy)-induced 
      endothelial damage. However, the underlying mechanism remains unknown. In this 
      study, we have investigated the effect of Ginsenoside Rb1 on Hcy-induced 
      endothelial dysfunction and its underlying signal pathway in vivo and in vitro. 
      Ginsenosides prevented Hcy-induced impairment of endothelium-dependent relaxation 
      and Rb1 reversed Hcy-induced reduction of NO production in a dose-dependent 
      manner as detected by nitrate reductase method. Rb1 activated serine-1177 
      phosphorylation of endothelial nitric oxide synthase (eNOS) and serine-473 
      phosphorylation of Akt, while inhibited threonine-495 phosphorylation of eNOS as 
      detected by western blotting. Rb1-induced phosphorylation of serine-1177 was 
      significantly inhibited by wortmannin, PI3K inhibitor or SH-5, an Akt inhibitor, 
      and partially reversed by Phorbol 12-myristate 13-acetate (PMA), a PKC activator. 
      PMA also stimulated phosphorylation of threonine-495 which was inhibited by Rb1. 
      Here we show for the first time that Rb1 prevents Hcy-induced endothelial 
      dysfunction via PI3K/Akt activation and PKC inhibition. These findings 
      demonstrate a novel mechanism of the action of Rb1 that may have value in 
      prevention of HHcy associated cardiovascular disease.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Lan, Tao-Hua
AU  - Lan TH
AD  - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen 
      University, Guangzhou, PR China.
FAU - Xu, Zhi-Wei
AU  - Xu ZW
FAU - Wang, Zhi
AU  - Wang Z
FAU - Wu, Yi-Ling
AU  - Wu YL
FAU - Wu, Wei-Kang
AU  - Wu WK
FAU - Tan, Hong-Mei
AU  - Tan HM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110414
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Ginsenosides)
RN  - 0 (von Willebrand Factor)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 7413S0WMH6 (ginsenoside Rb1)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*drug effects/physiology
MH  - Enzyme Activation
MH  - Ginsenosides/*pharmacology
MH  - Homocysteine/*toxicity
MH  - Male
MH  - Nitric Oxide/blood
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphorylation
MH  - Protein Kinase C/*antagonists & inhibitors
MH  - Proto-Oncogene Proteins c-akt/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Vasodilation/drug effects
MH  - von Willebrand Factor/analysis
EDAT- 2011/04/26 06:00
MHDA- 2011/08/06 06:00
CRDT- 2011/04/26 06:00
PHST- 2011/01/31 00:00 [received]
PHST- 2011/04/05 00:00 [revised]
PHST- 2011/04/06 00:00 [accepted]
PHST- 2011/04/26 06:00 [entrez]
PHST- 2011/04/26 06:00 [pubmed]
PHST- 2011/08/06 06:00 [medline]
AID - S0006-2952(11)00220-6 [pii]
AID - 10.1016/j.bcp.2011.04.001 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2011 Jul 15;82(2):148-55. doi: 10.1016/j.bcp.2011.04.001. Epub 
      2011 Apr 14.