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

W Ji1, B Q Gong

  • 1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, #453, 130 Meilong Road, Shanghai 200237, China. weiji1979@yahoo.com.cn

Insights

The n-butanol extract (NE3) from Panax notoginseng root acts as a dual Farnesoid X receptor (FXR)/Liver X receptor alpha (LXRalpha) agonist. This extract effectively lowers cholesterol and triglycerides in hyperlipidemic rats by modulating key lipid metabolism genes.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Natural Products

Background:

  • Maintaining normal lipid levels is crucial for health.
  • Liver X receptor alpha (LXRalpha) and Farnesoid X receptor (FXR) are key regulators of lipid homeostasis.
  • Dysregulation of lipid metabolism contributes to hyperlipidemia.

Purpose of the Study:

  • To evaluate the hypolipidemic effects of the n-butanol extract (NE3) from Panax notoginseng root.
  • To investigate the underlying mechanisms of NE3's action on lipid homeostasis.
  • To determine if NE3 acts as an agonist for FXR and/or LXRalpha.

Main Methods:

  • In vitro transactivation assays to identify receptor agonism.
  • In vivo study using Sprague-Dawley male rats fed a high-fat/high-cholesterol diet.
  • Oral administration of NE3 or vehicle, followed by serum and hepatic lipid level analysis.
  • Gene expression analysis of key lipid metabolism regulators (e.g., ABCA1, ABCG5, ABCG8, ApoCII, SHP, LDLR, CYP7A1, ApoCIII, SREBP1c).

Main Results:

  • NE3 demonstrated dual agonistic activity for both FXR and LXRalpha.
  • NE3 significantly and dose-dependently reduced serum and hepatic total cholesterol (TC), triglycerides (TG), and LDL-C levels.
  • NE3 upregulated LXRalpha target genes (ABCA1, ABCG5, ABCG8) and FXR target genes (ApoCII, SHP).
  • NE3 increased LDLR mRNA levels while decreasing CYP7A1, ApoCIII, and SREBP1c gene expression.

Conclusions:

  • NE3, a dual FXR/LXRalpha agonist, effectively prevents abnormal lipid accumulation in hyperlipidemic rats.
  • The hypolipidemic effects of NE3 are mediated through the modulation of LXRalpha and FXR signaling pathways.
  • Panax notoginseng root extract holds potential as a therapeutic agent for managing hyperlipidemia.