Beneficial effect of 3,4,5,6-tetrahydroxyxanthone on dyslipidemia in apolipoprotein E-deficient mice.
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.
Xiao
Hong-Bo
HB
College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China. xhbzhb@yahoo.com
Sun
Zhi-Liang
ZL
Lu
Xiang-Yang
XY
Li
Da-Zhi
DZ
Xu
Jian-Ping
JP
Hu
Ya-Ping
YP
D000273:Adipose Tissue / Q000378:metabolism; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000188:drug therapy*; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D013449:Sulfonamides / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D044004:Xanthones / Q000627:therapeutic use*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D001057:Apolipoproteins E; D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D008071:Lipoprotein Lipase; D012333:RNA, Messenger; D013449:Sulfonamides; D014280:Triglycerides; D044004:Xanthones; C518384:3,4,5,6-tetrahydroxyxanthone; C404495:Angptl3 protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides