Hypolipidemic effects and mechanisms of Panax notoginseng on lipid profile in hyperlipidemic rats.
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.
Ji
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State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, #453, 130 Meilong Road, Shanghai 200237, China. weiji1979@yahoo.com.cn
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D000284:Administration, Oral; D000818:Animals; D000440:Butanols / Q000737:chemistry; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors; D053723:Panax notoginseng / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D000440:Butanols; D002784:Cholesterol; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D006586:Hexanes; D000960:Hypolipidemic Agents; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010936:Plant Extracts; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides; D000099150:Receptor, Farnesoid X-Activated; C000605213:NR1H3 protein, human; C000605215:Nr1h3 protein, rat