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. T he presence of a large cluster of macrophage-derived foam cells in situ in the subendothelial spaces is one of the characteristic features of early stage atherosclerotic lesions. 1 Macrophages take up chemically-modified lowdensity lipoproteins (LDL), such as oxidized LDL (Ox-LDL) and acetylated LDL (acetyl-LDL) through the scavenger receptors 2 such as class A scavenger receptor (SR-A), 3 class B scavenger receptor (CD36), 4 and class B scavenger receptor type-I (SR-BI). 5 Because free cholesterol, which is incorporated into the cells with modified LDL through the scavenger receptors, is toxic to the cells, it is esterified to the cholesterol ester (CE) by acyl CoA: cholesterol acyltransferase (ACAT), an intracellular enzyme located in the rough endoplasmic reticulum. 6 These reactions change the macrophages to foam cells that are characterized by intracellular accumulation of CE. To date, 2 human ACAT isozymes (ACAT-1 and ACAT-2) are known. 7,8 ACAT-1 is highly expressed by macrophage-derived foam cells in atherosclerotic lesions and upregulated during monocytic differentiation into macrophages. 9 In addition, ACAT-1 is located in the Kuppfer cells of the liver, kidney, and adrenal cortical cells, whereas ACAT-2 is mainly located in hepatocytes and intestinal mucosal cells. 9 These findings are consistent with the notion that ACAT-1 plays a critical role in foam cell formation in macrophages; whereas ACAT-2 is responsible for the cholesterol absorption process in intestinal mucosal cells. 9 Because foam cell formation by these mechanisms is believed to play an essential role...

Viral respiratory infections may be associated with the virus-induced asthma in adults as well as children. Particularly, human rhinovirus is strongly suggested a major candidate for the associations of the virus-induced asthma. Thus, in this review, we reviewed and focused on the epidemiology, pathophysiology, and treatment of virus-induced asthma with special reference on human rhinovirus. Furthermore, we added our preliminary data regarding the clinical and virological findings in the present review.

It was previously revealed that esculeoside A, a new glycoalkaloid, and esculeogenin A, a new aglycon of esculeoside A, contained in ripe tomato ameliorate atherosclerosis in apoE-deficent mice. This study examined whether tomatidine, the aglycone of tomatine, which is a major tomato glycoalkaloid, also shows similar inhibitory effects on cholesterol ester (CE) accumulation in human monocyte-derived macrophages (HMDM) and atherogenesis in apoE-deficient mice. Tomatidine significantly inhibited the CE accumulation induced by acetylated LDL in HMDM in a dose-dependent manner. Tomatidine also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-CoA:cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that tomatidine suppresses both ACAT-1 and ACAT-2 activities. Furthermore, the oral administration of tomatidine to apoE-deficient mice significantly reduced levels of serum cholesterol, LDL-cholesterol, and areas of atherosclerotic lesions. The study provides the first evidence that tomatidine significantly suppresses the activity of ACAT and leads to reduction of atherogenesis.

Sapovirus (SaV) is an important pathogen that causes acute gastroenteritis in humans. Human SaV is highly diverse genetically and is classified into multiple genogroups and genotypes. At present, there is no clear evidence for gastroenteritis cases caused by re-infection with SaV. We found that two individuals were sequentially infected with SaVs of two different genogroups and had gastroenteritis after each infection, although in one of the subsequent cases, both SaV and norovirus were detected. We also found a genetic shift in SaVs from gastroenteritis outpatients in the same geographical location. Our results suggest that protective immunity may be at least genogroup-specific for SaV.