Longxuetongluo capsule inhibits atherosclerosis progression in high-fat diet-induced ApoE-/- mice by improving endothelial dysfunction

Atherosclerosis. 2016 Dec:255:156-163. doi: 10.1016/j.atherosclerosis.2016.08.022. Epub 2016 Aug 23.

Abstract

Background and aims: Chinese dragon's blood has been used to treat blood stasis for thousands of years. Its total phenolic extract (Longxuetongluo capsule, LTC) is used for the treatment of ischemic stroke; however, its protective effect against atherosclerosis remains poorly understood. This paper aims to investigate the antiatherosclerotic effect of LTC and the underlying mechanisms in high-fat diet (HFD)-induced ApoE-/- mice.

Methods: The levels of plasma lipid and areas of atherosclerotic lesions in the aortic sinus in ApoE-/- mice were evaluated. The effect of LTC on the nitric oxide (NO) production in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells (HUVECs) was determined. The adhesion of monocytes to ox-LDL-stimulated HUVECs was further studied.

Results: LTC at low, medium, and high doses markedly decreased the atherosclerotic lesion areas of the aortic sinus in HFD-induced ApoE-/- mice by 26.4% (p < 0.05), 30.1% (p < 0.05), and 46.5% (p < 0.01), respectively, although it did not improve the dyslipidemia. Furthermore, LTC restored the diminished NO production of ox-LDL-stimulated HUVECs (p < 0.001) and inhibited the adhesion between monocytes and endothelial cells (p < 0.01). LTC appeared to alleviate ox-LDL-stimulated dysfunction of HUVECs, and inhibit the adhesion of monocytes to HUVECs via the MAPK/IKK/IκB/NF-κB signaling pathway, thus decrease atherosclerotic lesions in the aortic sinus in HFD-induced ApoE-/- mice.

Conclusions: These findings suggest the potential of LTC for use as an effective agent against atherosclerosis.

Keywords: Anti-atherosclerosis; Chinese dragon's blood; Endothelial dysfunction; Longxuetongluo capsule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Diseases / genetics
  • Aortic Diseases / metabolism
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control*
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Cell Adhesion / drug effects
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Coculture Techniques
  • Diet, High-Fat*
  • Disease Models, Animal
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Genetic Predisposition to Disease
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Lipoproteins, LDL / pharmacology
  • Male
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Phenotype
  • Plaque, Atherosclerotic
  • Signal Transduction / drug effects
  • Sinus of Valsalva / drug effects*
  • Sinus of Valsalva / metabolism
  • Sinus of Valsalva / pathology
  • Time Factors

Substances

  • Apolipoproteins E
  • Drugs, Chinese Herbal
  • Lipoproteins, LDL
  • NF-kappa B
  • longxuetongluo
  • oxidized low density lipoprotein
  • Nitric Oxide
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Mitogen-Activated Protein Kinases