Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT
Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT
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DOI：
10.1161/atvbaha.107.147405
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发表时间：
2007-11-01
影响因子：
8.7
通讯作者：
Nagai, Ryoji
中科院分区：
文献类型：
--
作者：
Fujiwara, Yukio;Kiyota, Naoko;Nagai, Ryoji
我们最近发现了七叶皂苷A，一种新的螺茄烷型糖苷，在番茄中的含量是番茄红素的4倍。在本研究中，我们研究了七叶皂苷A和七叶皂苷元A（一种新的七叶皂苷元）的作用，方法和结果-在人单核细胞衍生的巨噬细胞（HMDM）中，以剂量依赖性方式抑制（乙酰-LDL），而不抑制甘油三酯的积累，然而，它并不抑制乙酰-LDL与细胞的结合。在过表达酰基辅酶A（CoA）：胆固醇酰基转移酶（ACAT）-1或ACAT-2的中国仓鼠卵巢细胞中，七叶皂苷元A也抑制CE的形成，表明七叶皂苷元A抑制ACAT-1和ACAT-2的活性。此外，七叶皂苷元A抑制ACAT-1蛋白的表达，而SR-A和SR-BI的表达不受抑制。口服给药的七叶皂苷A的载脂蛋白E缺陷的小鼠显着降低血清胆固醇，甘油三酯，低密度脂蛋白胆固醇的水平，和动脉粥样硬化病变的地区没有任何可检测到的副作用. Conclusions，我们的研究提供了第一个证据，纯化的七叶皂苷A显着抑制ACAT蛋白的活性，并导致减少动脉粥样硬化。
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 dosedependent 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.