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具有抗氧化活性的丁香酚抑制与人成纤维肉瘤细胞转移相关的 MMP-9。

Eugenol with antioxidant activity inhibits MMP-9 related to metastasis in human fibrosarcoma cells.

机构信息

Department of Chemistry, Dong-Eui University, Busan 614-714, Republic of Korea.

出版信息

Food Chem Toxicol. 2013 May;55:106-12. doi: 10.1016/j.fct.2012.12.050. Epub 2013 Jan 9.

Abstract

The oxidative damage of lipid, protein and DNA is known to be involved in chronic inflammation as well as metastasis. It has been highlighted for searching natural compounds without toxicity to prevent development of these diseases. Thus, it was investigated whether eugenol can inhibit matrix metalloproteinase (MMP) expression and activity as well as antioxidant effect. Eugenol was contained as a major ingredient in herbs such as clove and Magnoliae Flos. The direct scavenging effects of eugenol on DPPH radical, hydrogen peroxide, reducing power, lipid peroxidation and genomic DNA damage related to oxidative stress were evaluated in cell free system. It was observed that eugenol specifically exhibited higher inhibitory effect on hydrogen peroxide than other reactive oxygen species, and also blocked DNA oxidation and lipid peroxidation induced by hydroxyl radical. In addition, the inhibitory effects of eugenol on the activity and expression of MMP-9 activity related to metastasis were determined using gelatin zymography and western-blot. The data showed that it inhibited MMP-9 activities in PMA-stimulated HT1080 cells. Furthermore, it was found that eugenol exerts inhibitory effects on MMP-9 via inactivation of ERK. Therefore, these results suggest that eugenol could be available as an excellent agent for prevention of metastasis related to oxidative stress.

摘要

脂质、蛋白质和 DNA 的氧化损伤被认为与慢性炎症以及转移有关。人们已经强调要寻找没有毒性的天然化合物来预防这些疾病的发生。因此,研究了丁香酚是否可以抑制基质金属蛋白酶(MMP)的表达和活性以及抗氧化作用。丁香酚是许多草药如丁香和厚朴中的主要成分。在无细胞体系中评估了丁香酚对 DPPH 自由基、过氧化氢、还原能力、脂质过氧化和与氧化应激相关的基因组 DNA 损伤的直接清除作用。结果表明,丁香酚对过氧化氢的抑制作用明显高于其他活性氧,还能阻止羟基自由基诱导的 DNA 氧化和脂质过氧化。此外,还使用明胶酶谱法和 Western blot 法测定了丁香酚对与转移相关的 MMP-9 活性和表达的抑制作用。结果表明,它抑制了 PMA 刺激的 HT1080 细胞中 MMP-9 的活性。此外,还发现丁香酚通过 ERK 的失活对 MMP-9 发挥抑制作用。因此,这些结果表明丁香酚可作为预防与氧化应激相关的转移的有效药物。

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