Effects of 2-(2,4-dimethylphenyl)indan-1,3-dione on serum lipoprotein and lipid metabolism of rodents

Abstract

2-(2,4-Dimethylphenyl)indan-1,3-dione was shown to be a potent hypolipidemic agent in rodents, lowering significantly both serum cholesterol and triglyceride levels at 20 mg/kg/day. The agent in vivo inhibited the enzymatic activities of ATP-dependent citrate lyase, acetyl-CoA synthetase, cholesterol-7α-hydroxylase, acyl-CoA cholesterol acyl transferase,sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. Tissue lipid levels of liver and small intestine also were reduced by the agent. The rat serum lipoprotein lipid content was modulated by the drug, which should be favorable for the removable of cholesterol from peripheral tissue for conduction to the liver for clearance from the body. Low density lipoprotein (LDL) cholesterol levels were reduced after treatment, which suggests that the agent potentially reduces deposition of cholesterol in plaques. If chemotherapy for atherosclerosis is to be successful, then the high density lipoprotein (HDL) cholesterol level needs to be elevated more than 16% to 25%, the level produced by current hypolipidemic agents. 2-(2,4-Dimethylphenyl)-indan-1,3-dione offers a 75% increase in HDL cholesterol levels and a 30% reduction of LDL cholesterol levels with a suppression of de novo synthesis of lipids and a reduction of tissue cholesterol deposition.