Effects of artesunate and ursolic acid on hyperlipidemia and its complications in rabbit

Eur J Pharm Sci. 2013 Nov 20;50(3-4):366-71. doi: 10.1016/j.ejps.2013.08.003. Epub 2013 Aug 15.

Abstract

Objective: To find the novel hypolipidemic agents, the effects of ursolic acid and artesunate on hyperlipidemia and its complications were determined in rabbit fed with Western-type diet.

Methods and results: New Zealand rabbits fed a Western-type diet developed a hyperlipidemia. Rabbits received ursolic acid (25mg/kg) or artesunate (25mg/kg) alone, or in combination (12.5+12.5mg/kg), to prevent hyperlipidemia. Ursolic acid or artesunate alone significantly decreased the plasma cholesterol and triglyceride in rabbits. Furthermore, they both attenuated liver steatosis and reduced the area of aortic root lesions. The combination of ursolic acid and artesunate was more potent than either agent alone, which indicates a strong synergistic effect.

Conclusion: The hypolipidemic effect of artesunate is firstly reported. Its combination with ursolic acid might have the potential to further develop for the treatment of atherosclerosis.

Keywords: ABCA1; ATP binding cassette A1; Artesunate; Atherosclerosis; HDL; Hyperlipidemia; Inflammation; KLF2; LDLR; PPAR-α; SREBP1; Ursolic acid; VCAM-1; apoA-I; apolipoprotein A-I; high density lipoprotein; kruppel-like factor 2; low density lipoprotein receptor; peroxisome proliferators-activated receptors-α; sterol regulatory element-binding protein-1; vascular cell adhesion molecule-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / pathology
  • Apolipoprotein A-I / genetics
  • Apolipoprotein A-I / metabolism
  • Artemisinins / administration & dosage*
  • Artesunate
  • Cholesterol / blood
  • Drug Therapy, Combination
  • Fatty Liver / drug therapy*
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Hyperlipidemias / complications
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / metabolism
  • Hyperlipidemias / pathology
  • Hypolipidemic Agents / administration & dosage*
  • Kruppel-Like Transcription Factors / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • PPAR alpha / genetics
  • Rabbits
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Triglycerides / blood
  • Triterpenes / administration & dosage*
  • Ursolic Acid
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Apolipoprotein A-I
  • Artemisinins
  • Hypolipidemic Agents
  • Kruppel-Like Transcription Factors
  • PPAR alpha
  • Receptors, LDL
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Triterpenes
  • Vascular Cell Adhesion Molecule-1
  • Artesunate
  • Cholesterol