PMID- 20801605
OWN - NLM
STAT- MEDLINE
DCOM- 20110131
LR  - 20161125
IS  - 1097-6809 (Electronic)
IS  - 0741-5214 (Linking)
VI  - 53
IP  - 1
DP  - 2011 Jan
TI  - The effects of ginsenoside Rb1 on endothelial damage and ghrelin expression 
      induced by hyperhomocysteine.
PG  - 156-64
LID - 10.1016/j.jvs.2010.06.170 [doi]
AB  - OBJECTIVE: Studies have indicated that ginsenoside Rb1 and ghrelin could both 
      prevent homocysteine (Hcy)-induced endothelial dysfunction through the 
      endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) mechanism. This study 
      investigated whether endogenous ghrelin mediates the endothelial protection of 
      ginsenosidee Rb1 through in vitro and in vivo experiments. METHODS: Rats were 
      randomized into a control group, a hyperhomocysteine (HHcy) model group with a 
      high methionine diet, a ginsenosides (GS) group, and HHcy plus GS group. Plasma 
      ghrelin was detected by enzyme-linked immunosorbent assay. Aortic rings for 
      control and HHcy groups were treated with ghrelin or not. Endothelium-dependent 
      vasodilatation function was evaluated by the aortic ring assay, and the 
      structural changes were visualized by hematoxylin and eosin staining. Human 
      umbilical vein endothelial cells (HUVECs) were cultured, and the experimental 
      conditions were optimized according to NO production. After treatment, the NO, 
      ghrelin, and von Willebrand factor (vWF) levels in the media were detected and 
      analyzed with linear regression. Ghrelin and eNOS expression were observed by 
      cell immunohistochemical staining. Ghrelin receptor antagonist was used to detect 
      the mechanism of ginsenoside Rb1 on NO production, which was reflected by 
      diacetylated 4,5-diaminofluorescein-2 diacetate fluorescence. RESULTS: In vivo 
      experiments demonstrated that plasma ghrelin levels in the HHcy group were 
      significantly elevated vs controls (P < .05) and were significantly increased in 
      the HHcy plus GS group (P < .01). Compared with control, endothelium-dependent 
      vasodilatation function was greatly reduced in the HHcy group (P < .01), which 
      was significantly increased in HHcy plus ghrelin group compared with HHcy group 
      (P < .01). The arterial walls of HHcy group exhibited characteristic pathologic 
      changes, which were repaired in HHcy plus ghrelin group. In vivo, compared with 
      Hcy (200 muM) group, HUVECs pretreated with ginsenoside Rb1 (10 muM) for 30 minutes 
      showed significant increases in NO and ghrelin levels and evident reduction in 
      vWF levels. Linear regression analysis demonstrated that ghrelin levels were 
      significantly positively correlated with NO levels and significantly negatively 
      correlated with vWF levels. The addition of Rb1 to Hcy also greatly reversed 
      Hcy-induced downregulation of ghrelin and eNOS expression. Ghrelin inhibition 
      significantly abolished the upregulation of NO levels induced by Rb1. CONCLUSION: 
      Ghrelin can prevent Hcy-induced vascular endothelial dysfunction and structural 
      damage. The compensatory elevation of plasma ghrelin levels in an Hcy-induced 
      endothelial injury model may be a protective response. Ginsenoside Rb1 can 
      significantly stimulate the ghrelin endocrine to inhibit endothelial injury. 
      Ginsenoside also upregulates the NO signaling pathway reduced by Hcy through the 
      ghrelin molecular mechanism.
CI  - Copyright (c) 2011 Society for Vascular Surgery. Published by Mosby, Inc. All 
      rights reserved.
FAU - Xu, Zhiwei
AU  - Xu Z
AD  - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen 
      University, Guangzhou, Peoples Republic of China.
FAU - Lan, Taohua
AU  - Lan T
FAU - Wu, Weikang
AU  - Wu W
FAU - Wu, Yiling
AU  - Wu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (Ghrelin)
RN  - 0 (Ginsenosides)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 7413S0WMH6 (ginsenoside Rb1)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Endothelium, Vascular/drug effects/*pathology/physiology
MH  - Ghrelin/*blood
MH  - Ginsenosides/*pharmacology
MH  - Homocysteine/*pharmacology
MH  - Immunohistochemistry
MH  - Male
MH  - Nitric Oxide/physiology
MH  - Nitric Oxide Synthase Type III/physiology
MH  - *Panax
MH  - Rats
MH  - Rats, Wistar
MH  - Umbilical Veins
MH  - Vasodilation/*drug effects/physiology
EDAT- 2010/08/31 06:00
MHDA- 2011/02/01 06:00
CRDT- 2010/08/31 06:00
PHST- 2010/03/09 00:00 [received]
PHST- 2010/06/16 00:00 [revised]
PHST- 2010/06/27 00:00 [accepted]
PHST- 2010/08/31 06:00 [entrez]
PHST- 2010/08/31 06:00 [pubmed]
PHST- 2011/02/01 06:00 [medline]
AID - S0741-5214(10)01676-9 [pii]
AID - 10.1016/j.jvs.2010.06.170 [doi]
PST - ppublish
SO  - J Vasc Surg. 2011 Jan;53(1):156-64. doi: 10.1016/j.jvs.2010.06.170.