Department of Biochemistry and Molecular Biology, Ernesto Quagliariello, University of Bari, Via Orabona 4, 70126, Bari, Italy.
Neurochem Res. 2011 Mar;36(3):518-27. doi: 10.1007/s11064-010-0373-2. Epub 2011 Jan 5.
We investigated whether polyphenols modulate the expression and activity of the enzymes gelatinases A (MMP-2) and B (MMP-9), involved in the pathogenesis of multiple sclerosis (MS). LPS-activated primary rat astrocytes were treated with the flavonoids quercetin (QRC) and cathechins [green tea extract (GTE)] and the non-flavonoids resveratrol (RSV) and tyrosol/hydroxytyrosol (Oliplus). As assessed by zymography and RT-PCR, RSV and Oliplus, but not QRC and GTE, dose-dependently inhibited the LPS-induced levels and mRNA expression of MMP-2 and MMP-9. By contrast, in cell-free systems direct inhibition of gelatinase activity in MS sera was determined by QRC and GTE, but not by RSV. Oliplus was only partially effective. Our results indicate that the flavonoids and non-flavonoids tested exert their inhibitory effect on MMPs, displaying different mechanisms of action, possibly related to their structure. Therefore, their combined use may represent a powerful tool for the down-regulation of MMPs in the course of MS.
我们研究了多酚是否调节明胶酶 A（MMP-2）和 B（MMP-9）的表达和活性，这些酶参与多发性硬化症（MS）的发病机制。用黄酮类化合物槲皮素（QRC）和儿茶素[绿茶提取物（GTE）]以及非黄酮类化合物白藜芦醇（RSV）和酪氨酸/羟基酪氨酸（Oliplus）处理 LPS 激活的原代大鼠星形胶质细胞。通过酶谱法和 RT-PCR 评估，RSV 和 Oliplus 但不是 QRC 和 GTE 以剂量依赖性抑制 LPS 诱导的 MMP-2 和 MMP-9 的水平和 mRNA 表达。相比之下，在无细胞系统中通过 QRC 和 GTE 直接抑制 MS 血清中的明胶酶活性，但 RSV 则不然。Oliplus 仅部分有效。我们的结果表明，测试的黄酮类化合物和非黄酮类化合物对 MMP 发挥抑制作用，表现出不同的作用机制，可能与其结构有关。因此，它们的联合使用可能代表了下调 MS 过程中 MMP 的有力工具。
