| Co-Investigator(Kenkyū-buntansha) |
IKAI Kohichi Kurashiki Sakuyo University, Food Culture, Nutritional Sciences, Professor, 食文化学部・栄養学科, 教授 (00135568)
NAGASAWA Haruko Kurashiki Sakuyo University, Food Culture, Nutritional Sciences, Professor, 食文化学部・栄養学科, 教授 (50164413)
KIMURA Mariko Kurashiki Sakuyo University, Food Culture, Food System, Instructor, 食文化学部・フードシステム学科, 講師 (00351932)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Several functional foods were found to stimulate antithrombotic properties of vascular endothelial cell. When the extracts from such foods were added to the medium of cultured human umbilical vein endothelial cells (HUVECs), the cells increased the secretion of tissue-type plasminogen activator (t-PA) and/or decreased that of type 1 plasminogen activator inhibitor (PAT-1), thus resulting in significantly enhanced fibrinolytic activity. Extracts from black beans with hot water down-regulated PAI-1 secretion without changing t-PA secretion from HUVECs. Interestingly, several extracts from the beans inhibited t-PA-mediated plasminogen activation, but stimulated t-PA release from HUVECs. One of domestic fermented teas showed the benefit effects on antithrombotic vectors of HUVECs in which the cells maintained normal levels of t-PA secretion but considerably reduced PAI-1 secretion. These effects may be probably attributed to the high content of gallic acid but not lactic acid both of which
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are specific in the fermented tea., since gallic acid itself considerably suppressed PAI-1 secretion from HUVECs. Vinegars were also investigated for their functional activities on HUVECs. A few kinds of vinegars typically increased t-PA secretion without changing PAI-1 secretion. The main component responsible for the up-regulated t-PA release was acetic acid. This increase in t-PA secretion was specific for acetic acid, since other organic or inorganic acids such as lactate, citrate, or phosphate did not exert such effects. The most advantageous vinegar was made from millet. Thus, we can classify the antithrombotic foods into three types, 1)t-PA enhancer such as vinegar, 2)PAI-1 reducer such as tea, and 3)both t-PA enhancer and PAI-1 reducer such as black bean. The combination of these substances will be more effective on the promotion of antithombotic activities of endothelial cells. The typical polyphenolics, catechin, quercetin and resveratrol were also tested. They increased t-PA secretion without any effects on PAI-1 secretion. As, resveratrol (RES) was found to be the most strong t-PA enhancer, trans-RES was used for an ingredient of high fat diet for apoE-/-/LDL-R-/- mice that were genetically hypercholesterolemic. If the mice were fed with t-RES containing diet, it significantly reduced the atherogenesis of aorta as well as He-Ne laser-induced thrombogenesis on carotid artery. Thus, such polyphenol is available in antithrombotic activity in vivo. Finally, the model system for diabetic plasma was prepared by culturing HUVECs with high concentration of glucose. The antithrombotic potential of HUVECs was hampered by the reduction of t-PA secretion and the increase of PAI-1 secretion. Furthermore, both the expression of t-PA receptor and the response of fibrin clot were also suppressed. However, these abnormalities were dramatically improved in the presence of the fermented tea or the millet vinegar, demonstrating that these foodstuffs possess the beneficial effect that prevents some developments to vascular damages caused by diabetes mellitus. Less
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