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KMID : 1012320030060010025
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Nutritional Sciences
2003 Volume.6 No. 1 p.25 ~ p.30
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Regulation of cyclooxygenase-2 and mapkinases by isoflavones in ovariectomized and estrogen-supplemented mature female rats fed a high fat-high cholesterol diet
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Shin Jang-In
Park Ock-Jin
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Abstract
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The effects of soy-isoflavones, which are phytoestrogens derived from plants with a flavonoid structure, on cyclooxygenase -2 (COX-2) expression, PGE2 production, and mapkinases expression, were investigated in experimentally-induced atherogenic rats by feeding a high fat-high cholesterol diet. Female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were randomized to the following treatments for an eight-week experimental period: 17β-estradiol (200 g/kg diet), low concentration of isoflavones (0.8g/kg diet), and high concentration of isoflavones (4.0g/kg diet). In the group supplemented with a high dose of isoflavones, COX-2 expression was down-regulated. This down-regulation was accompanied by a reduced expression of pERK1/2. In the second experiment using 48-week old female Sprague-Dawly rats, the effects of isoflavones and estrogen were compared in the basal estrogen-supplementation at the level of 600μ g/kg diet. Isoflavones induced the marked down-regulation of COX-2 protein and the decrease in PGE2 production in estrogen supplemented states and this was followed by the down-regulation of p38 among mapkinases. The two different mapkinases are involved in the down-regulation of COX-2 depending on estrogen-deficient and estrogen supplemented states. This kind of COX-2 down-regulation by isoflavones was not observed in the different tissue, mammary glands. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by isoflavonesin the absence or the presence of estrogen ave required in vivo system of female rats.
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KEYWORD
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Isoflavones, COX-2 expression, mapkinases, ovariectomized rats, mature estrogen-supplemented rats, prostaglandin production
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