Hypolipidemic effects and mechanisms of Panax notoginseng on lipid profile in hyperlipidemic rats

J Ethnopharmacol. 2007 Sep 5;113(2):318-24. doi: 10.1016/j.jep.2007.06.022. Epub 2007 Jul 4.

Abstract

Maintenance of normal lipid levels has implicated the involvement of genes induced by liver X receptor alpha (LXRalpha) and Farnesoid X receptor (FXR). This study was designed to evaluate the hypolipidemic effects of n-butanol extract (NE3) of Panax notoginseng (Burk.) F.H. Chen root on lipid homeostasis and investigate the possible mechanisms in animal experiments. In the transactivation assays, NE3 was identified as a dual FXR/LXRalpha agonist. Subsequently, Sprague-Dawley male rats on a high-fat/high-cholesterol diet were treated orally with NE3 or vehicle alone. As expected, the concentrations of serum TC, TG and LDL-C in rats treated with various concentrations of NE3 showed significant (P<0.01) and dose-dependent decrease, respectively, accompanied with a significant (P<0.01) and dose-dependent decrease in the concentration of hepatic TC and TG. Express-level analysis indicated that both LXRalpha target genes including ABCA1, ABCG5, ABCG8 and FXR target genes including ApoCII and SHP were significantly induced by NE3 (P<0.01). Interestingly, LDLR mRNA level was significantly higher by NE3 (P<0.01), accompanied with the significantly decreased expression levels of CYP7A1, ApoCIII and SREBP1c genes (P<0.01). Based on these results, it can be concluded that NE3 as a dual FXR/LXRalpha agonist largely prevented the accumulation of abnormal lipid in the hyperlipidemic rats.

MeSH terms

  • Administration, Oral
  • Animals
  • Butanols / chemistry
  • Cell Line, Tumor
  • Cholesterol / blood
  • Cholesterol / metabolism
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / metabolism
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Hexanes / chemistry
  • Humans
  • Hyperlipidemias / blood
  • Hyperlipidemias / prevention & control*
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / isolation & purification
  • Hypolipidemic Agents / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • Liver X Receptors
  • Male
  • Orphan Nuclear Receptors
  • Panax notoginseng / chemistry*
  • Plant Extracts / administration & dosage
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transfection
  • Triglycerides / blood
  • Triglycerides / metabolism

Substances

  • Butanols
  • Cholesterol, HDL
  • DNA-Binding Proteins
  • Hexanes
  • Hypolipidemic Agents
  • Liver X Receptors
  • NR1H3 protein, human
  • Nr1h3 protein, rat
  • Orphan Nuclear Receptors
  • Plant Extracts
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Triglycerides
  • farnesoid X-activated receptor
  • Cholesterol