Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT

Arterioscler Thromb Vasc Biol. 2007 Nov;27(11):2400-6. doi: 10.1161/ATVBAHA.107.147405. Epub 2007 Sep 13.


Objective: We recently identified esculeoside A, a new spirosolane-type glycoside, with a content in tomatoes that is 4-fold higher than that of lycopene. In the present study, we examined the effects of esculeoside A and esculeogenin A, a new aglycon of esculeoside A, on foam cell formation in vitro and atherogenesis in apoE-deficient mice.

Methods and results: Esculeogenin A significantly inhibited the accumulation of cholesterol ester (CE) induced by acetylated low density lipoprotein (acetyl-LDL) in human monocyte-derived macrophages (HMDM) in a dose-dependent manner without inhibiting triglyceride accumulation, however, it did not inhibit the association of acetyl-LDL to the cells. Esculeogenin A also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-coenzymeA (CoA): cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that esculeogenin A suppresses the activity of both ACAT-1 and ACAT-2. Furthermore, esculeogenin A prevented the expression of ACAT-1 protein, whereas that of SR-A and SR-BI was not suppressed. Oral administration of esculeoside A to apoE-deficient mice significantly reduced the levels of serum cholesterol, triglycerides, LDL-cholesterol, and the areas of atherosclerotic lesions without any detectable side effects.

Conclusions: Our study provides the first evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy*
  • CHO Cells
  • Cells, Cultured
  • Cholesterol Esters / metabolism
  • Cricetinae
  • Cricetulus
  • Esculin / pharmacology*
  • Foam Cells / drug effects*
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Macrophages / drug effects
  • Mice
  • Mice, Knockout
  • Plant Extracts / pharmacology*
  • Sapogenins / pharmacology*
  • Sterol O-Acyltransferase / drug effects*


  • Cholesterol Esters
  • Plant Extracts
  • Sapogenins
  • Esculin
  • Sterol O-Acyltransferase