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

Abstract

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.

• Authors: Yukio Fujiwara, Naoko Kiyota, Masaharu Hori, Sayaka Matsushita, Yoko Iijima, Koh Aoki, Daisuke Shibata, Motohiro Takeya, Tsuyoshi Ikeda, Toshihiro Nohara, Ryoji Nagai
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 27 Issue 11 Pg. 2400-6 (Nov 2007) ISSN: 1524-4636 [Electronic] United States
• PMID: 17872457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)