Beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia in apolipoprotein E-deficient mice.

Abstract

Previous investigations have shown that decreased expression of angiopoietin-like protein 3 (Angptl3) is protective against dyslipidemia in atherosclerosis. The present study was conducted to test the effect of 3,4,5,6-tetrahydroxyxanthone, a xanthone compound, on dyslipidemia in apolipoprotein E-deficient (ApoE-/-) mice. Forty mice were randomly divided into 4 groups (n = 10): control group (C57BL/6J mice), ApoE-/-mice group, and two groups of ApoE-/- mice treated with 3,4,5,6-tetrahydroxyxanthone (10 or 30 mg/kg per day). Eight weeks after treatment, lipid levels in the blood and liver, expression of hepatic Angptl3, and adipose tissue lipoprotein lipase (LPL) were determined. Treatment with 3,4,5,6-tetrahydroxyxanthone (10 or 30 mg/kg) significantly decreased plasma and hepatic total cholesterol and triglyceride concentrations, increased plasma high-density lipoprotein cholesterol, and significantly downregulated expression of Angptl3 mRNA and protein concomitantly with upregulated expression of LPL mRNA. In addition, T0901317 (a liver X receptor ligand) caused elevated expression of hepatic Angptl3 mRNA and protein, and the effect of T0901317 was also abrogated by 3,4,5,6-tetrahydroxyxanthone in vivo and in vitro. The present results suggest that the beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia may be related to reduced expression of Angptl3.

• Authors: Hong-Bo Xiao, Zhi-Liang Sun, Xiang-Yang Lu, Da-Zhi Li, Jian-Ping Xu, Ya-Ping Hu
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 86 Issue 12 Pg. 815-26 (Dec 2008) ISSN: 0008-4212 [Print] Canada
• PMID: 19088802 (Publication Type: Journal Article)

Chemical References

• 3,4,5,6-tetrahydroxyxanthone
• Angiopoietin-Like Protein 3
• Angiopoietin-like Proteins
• Angiopoietins
• Angptl3 protein, mouse
• Apolipoproteins E
• Hydrocarbons, Fluorinated
• RNA, Messenger
• Sulfonamides
• T0901317
• Triglycerides
• Xanthones
• Cholesterol
• Lipoprotein Lipase

Topics

• Adipose Tissue (metabolism)
• Angiopoietin-Like Protein 3
• Angiopoietin-like Proteins
• Angiopoietins (metabolism)
• Animals
• Apolipoproteins E (deficiency, genetics)
• Cells, Cultured
• Cholesterol (blood, metabolism)
• Disease Models, Animal
• Dyslipidemias (drug therapy)
• Hydrocarbons, Fluorinated (pharmacology)
• Lipoprotein Lipase (metabolism)
• Liver (metabolism)
• Male
• Mice
• Mice, Knockout
• RNA, Messenger (analysis)
• Random Allocation
• Sulfonamides (pharmacology)
• Triglycerides (blood, metabolism)
• Xanthones (therapeutic use)