title: SCM-198 attenuates early atherosclerotic lesions in hypercholesterolemic rabbits via modulation of the inflammatory and oxidative stress pathways.
abstract: 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-α (TNF-α), as well as the mRNA levels of VCAM-1, IL-6, TNF-α, 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.
authors: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Yanfei
authors: Y
authors: Zhang
authors: Wei
authors: W
authors: Guo
authors: Yadan
authors: Y
authors: Wen
authors: Qinghui
authors: Q
authors: Xiong
authors: Hongrui
authors: H
authors: Liu
authors: Jian
authors: J
authors: Wu
authors: Yunzeng
authors: Y
authors: Zou
authors: Yizhun
authors: Y
authors: Zhu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005707:Gallic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018932:Chemokine CCL2; D015850:Interleukin-6; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C013587:leonurine; D018799:Intercellular Adhesion Molecule-1; D005707:Gallic Acid