Hypolipidemic effects and mechanisms of Panax notoginseng on lipid profile in hyperlipidemic rats
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1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, #453, 130 Meilong Road, Shanghai 200237, China. weiji1979@yahoo.com.cn
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.
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.