Hypolipidaemic mechanisms of action of CM108 (a flavone derivative) in hyperlipidaemic rats.
In the present study, the molecular mechanisms by which CM108, a flavone derivative, improves lipid profiles were investigated further. Hyperlipidaemia was induced by oral administration of high cholesterol and fat. After 4 weeks of treatment, the lipid levels in the serum, liver and faeces were measured and the liver genes involved in lipid metabolism were analysed to explore the molecular mechanisms of lowering lipids. CM108 modulated lipid profiles, including elevating the level of high-density lipoprotein cholesterol (HDL-C; 40%) and reducing serum levels of triglyceride (10%), total cholesterol (10%) and low-density lipoprotein cholesterol (26%). Levels of triglyceride and total cholesterol in the liver were reduced by 18% and 24%, respectively. Increased HDL-C level was attributed to the synergic effects of CM108 in increasing levels of ATP-binding cassette transporter (ABC)A1, apolipoprotein AI and apolipoprotein AII in the liver. Intriguingly, CM108 induced genes, including fatty acid transport protein, acyl-CoA synthetase and lipoprotein lipase that are important for more efficient fatty acid beta-oxidation, thereby reducing serum and liver triglyceride levels. In addition, induction of ABCG5, ABCG8 and cholesterol 7alpha-hydroxylase contributed to cholesterol metabolism, leading to decreases in serum and liver cholesterol levels. Thus, the genes involved in lipid metabolism were systemically modulated by CM108, which contributed to the improvement of lipid profiles in hyperlipidaemic rats.
Ji
Wei
W
Department of Bioengineering, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China. weiji1979@yahoo.com.cn
Guo
Lei
L
Lian
Jihong
J
Gong
Bangqiang
B
D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000187:drug effects / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000187:drug effects / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008074:Lipoproteins / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; C480692:Abcg5 protein, rat; C480693:Abcg8 protein, rat; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; C516924:CM108; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D047309:Flavones; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase