Structure-Activity Relationship of Resveratrol and Its Analogue, 4,4′-Dihydroxy-Trans-Stilbene, Toward the Endothelin Axis in Human Endothelial Cells
Structure-Activity Relationship of Resveratrol and Its Analogue, 4,4′-Dihydroxy-Trans-Stilbene, Toward the Endothelin Axis in Human Endothelial Cells
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DOI：
10.1089/jmf.2010.0272
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发表时间：
2011-10-01
影响因子：
2.4
通讯作者：
Savio, Monica
中科院分区：
文献类型：
--
作者：
Coppa, Tania;Lazze, Maria Claudia;Savio, Monica
白藜芦醇抑制血管张力调节剂内皮素1。我们合成了白藜芦醇类似物4，4‘-二羟基-反式二苯乙烯，在4和4’位分别带有2个羟基，得到了比白藜芦醇(3，4‘，5-三羟基-反式-二苯乙烯)更具活性的分子。结果表明，4，4‘-二羟基-反式-二苯乙烯可显著降低人内皮细胞内皮素-1的总分泌量和内皮素-1信使核糖核酸水平。此外，白藜芦醇及其类似物可降低内皮素转换酶-1的mRNA水平，并进一步降低该酶的活性。4，4‘-二羟基-反式二苯乙烯比白藜芦醇具有更高的活性，因为即使在较低的浓度下，新分子也能在内皮素合成和转化水平上发挥更大的活性。4，4‘-二羟基-反式-二苯乙烯和白藜芦醇虽然能抑制细胞内活性氧的形成和脂质过氧化，但不同氧化剂处理细胞后，并不影响ET-1的释放。这一发现表明，抑制内皮素-1的分泌与这两个化合物的抗氧化特性无关。基于这些结果，白藜芦醇类似物4，4‘-二羟基-反式二苯乙烯可能是一种很有前途的心血管疾病的化学预防药物。
Resveratrol inhibits endothelin-1, a vascular tension regulator. We synthesized the resveratrol analogue 4,4'-dihydroxy-trans-stilbene with 2 hydroxyl groups in the 4 and 4' position to obtain a molecule more active than resveratrol (3,4',5-trihydroxy-trans-stilbene). The results demonstrate that 4,4'-dihydroxy-trans-stilbene led to a significant decrease in total endothelin-1 secretion and in endothelin-1 messenger RNA (mRNA) levels in human endothelial cells. In addition, resveratrol and its analogue decreased endothelin-converting enzyme-1 mRNA levels and further reduced the activity of the enzyme. 4,4'-dihydroxy-trans-stilbene was more active than resveratrol because the new molecule exerted greater activity at the level of endothelin synthesis and conversion, even at a lower concentration. Although 4,4'-dihydroxy-trans-stilbene and resveratrol inhibited formation of reactive oxygen species and lipid peroxidation, the treatment of cells with different oxidant agents did not modify the endothelin-1 release. This finding suggests that the inhibition of endothelin-1 secretion is independent of the antioxidant properties of the 2 compounds. On the basis of these results, the resveratrol analogue 4,4'-dihydroxy-trans-stilbene could be a promising chemopreventive agent against cardiovascular diseases.