title: Antihyperlipidemic activity of sesquiterpene lactones and related compounds.
abstract: Some naturally occurring pseudoguaianolides and germacranolides as well as synthetic related compounds were observed to be antihyperlipidemic agents in mice. Several of these compounds at a dose of 20 mg/kg/day resulted in lowering of serum cholesterol by approximately 30% and of serum triglycerides by approximately 25%. Thiol-bearing enzymes of lipid synthesis, i.e., acetyl-CoA, citrate-lyase, acetyl-CoA synthetase, and beta-hydroxy-beta-methylglutaryl-CoA reductase, were inhibited by these agents in vitro, supporting the premise that these agents alkylate thiol nucleophiles by a Michael-type addition. The alpha-methylene-gamma-lactone moiety, the beta-unsubstituted cyclopentenone ring, and the alpha-epoxycyclopentanone system of these compounds appeared to be responsible for the lowering of serum lipids.
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D004353:Drug Evaluation, Preclinical; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood
chemical_list: D000960:Hypolipidemic Agents; D012717:Sesquiterpenes; D014280:Triglycerides; D002784:Cholesterol