PMID- 22840690
OWN - NLM
STAT- MEDLINE
DCOM- 20130116
LR  - 20131121
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 224
IP  - 1
DP  - 2012 Sep
TI  - SCM-198 attenuates early atherosclerotic lesions in hypercholesterolemic rabbits 
      via modulation of the inflammatory and oxidative stress pathways.
PG  - 43-50
LID - 10.1016/j.atherosclerosis.2012.06.066 [doi]
AB  - OBJECTIVE: To investigate SCM-198 (also known as "leonurine"), a compound in 
      Herba leonuri, as well as its effect on the progression of atherosclerosis in 
      hypercholesterolemic rabbits and underlying mechanisms. METHODS: Thirty New 
      Zealand male White rabbits (5 groups, n = 6) were fed either a normal diet or a 
      high-cholesterol diet (1%). The rabbits on the high-cholesterol diet received 
      treatments of low, moderate, and high doses of SCM-198 and placebo concurrently. 
      Eight weeks later, the animals underwent ultrasonographic imaging. They were then 
      sacrificed for further pathological and molecular biological analysis. RESULTS: 
      SCM-198-treated rabbits showed a significant alleviation in the development of 
      atherosclerosis in a dose-dependent manner. The lesions were smaller after the 
      SCM-198 treatments. In addition, the elasticity of the arteries and hemodynamic 
      status improved, accompanied with a decrease in smooth muscle cell migration and, 
      macrophage infiltration, as well as the expression of platelet-endothelial cell 
      adhesion molecule-1 (PECAM-1) in the aortas. Marginal changes in the lipid 
      parameters were found in the SCM-198-treated rabbits, with high-density lipid 
      cholesterol (HDL-C) elevation and triglyceride (TG) reduction at the high dose. 
      SCM-198 treatment dose-dependently reduced levels of serum soluble vascular cell 
      adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 
      (sICAM-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as well as 
      the mRNA levels of VCAM-1, IL-6, TNF-alpha, monocyte chemoattractant protein-1 
      (MCP-1), iNOS and MMP-9 in the aorta. In addition, SCM-198 also dose-dependently 
      increased the total antioxidant capacities and in parallel decreased the lipid 
      peroxidation levels in the serum and liver. The antioxidant effects of SCM-198 
      were implicated by the enhanced activities of catalase (CAT), superoxide 
      dismutase (SOD), glutathione peroxidase (GPx) and levels of glutathione (GSH) in 
      the liver, as well as the mRNA levels of CAT, SOD-1 and GPx in the aorta. 
      CONCLUSIONS: In a rabbit atherosclerotic model, SCM-198 dose-dependently 
      ameliorated the progression of atherosclerotic lesions and vascular dysfunction 
      accompanied by the suppression of inflammatory factors and oxidative stress. 
      These findings suggested that SCM-198 might be a potential agent for the 
      treatment of atherosclerosis.
CI  - Crown Copyright (c) 2012. Published by Elsevier Ireland Ltd. All rights reserved.
FAU - Zhang, Yanfei
AU  - Zhang Y
AD  - Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 
      201203, China.
FAU - Guo, Wei
AU  - Guo W
FAU - Wen, Yadan
AU  - Wen Y
FAU - Xiong, Qinghui
AU  - Xiong Q
FAU - Liu, Hongrui
AU  - Liu H
FAU - Wu, Jian
AU  - Wu J
FAU - Zou, Yunzeng
AU  - Zou Y
FAU - Zhu, Yizhun
AU  - Zhu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120707
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipids)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 09Q5W34QDA (leonurine)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 632XD903SP (Gallic Acid)
SB  - IM
CIN - Atherosclerosis. 2012 Sep;224(1):37-8. PMID: 22560329
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Antioxidants/*therapeutic use
MH  - Atherosclerosis/pathology/*prevention & control
MH  - Chemokine CCL2/biosynthesis
MH  - Gallic Acid/administration & dosage/*analogs & derivatives/therapeutic use
MH  - Hypercholesterolemia/drug therapy
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Interleukin-6/biosynthesis
MH  - Lipid Peroxidation/drug effects
MH  - Lipids/blood
MH  - Male
MH  - Rabbits
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Vascular Cell Adhesion Molecule-1/biosynthesis
EDAT- 2012/07/31 06:00
MHDA- 2013/01/17 06:00
CRDT- 2012/07/31 06:00
PHST- 2011/07/29 00:00 [received]
PHST- 2012/06/26 00:00 [revised]
PHST- 2012/06/26 00:00 [accepted]
PHST- 2012/07/31 06:00 [entrez]
PHST- 2012/07/31 06:00 [pubmed]
PHST- 2013/01/17 06:00 [medline]
AID - S0021-9150(12)00442-X [pii]
AID - 10.1016/j.atherosclerosis.2012.06.066 [doi]
PST - ppublish
SO  - Atherosclerosis. 2012 Sep;224(1):43-50. doi: 
      10.1016/j.atherosclerosis.2012.06.066. Epub 2012 Jul 7.