Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 113, Issue 2, Pages 318-324Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2007.06.022
Keywords
liver x receptor alpha; famesoid x receptor; Panax notoginsen; hypolipidemic
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Maintenance of normal lipid levels has implicated the involvement of genes induced by liver X receptor alpha (LXR alpha) and Famesoid 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/LXR alpha 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 LXRa 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/LXR alpha agonist largely prevented the accumulation of abnormal lipid in the hyperlipidemic rats. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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