| Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT. | |
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MedLine Citation:
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PMID: 17872457 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yukio Fujiwara; Naoko Kiyota; Masaharu Hori; Sayaka Matsushita; Yoko Iijima; Koh Aoki; Daisuke Shibata; Motohiro Takeya; Tsuyoshi Ikeda; Toshihiro Nohara; Ryoji Nagai |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-09-13 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 27 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2007 Nov |
Date Detail:
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Created Date: 2007-10-18 Completed Date: 2007-11-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2400-6 Citation Subset: IM |
Affiliation:
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Department of Medical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Honjo, 1-1-1, Kumamoto 860-8556, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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* |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol Esters; 0/Plant Extracts; 0/Sapogenins; 531-75-9/Esculin; EC 2.3.1.26/Sterol O-Acyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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