Braga Pier Carlo, Dal Sasso Monica, Culici Maria, Bianchi Tiziana, Bordoni Luca, Marabini Laura
Department of Pharmacology, School of Medicine, University of Milan, Milan, Italy.
Pharmacology. 2006;77(3):130-6. doi: 10.1159/000093790. Epub 2006 Jun 7.
Elastase, a serine proteinase released by activated human neutrophils, can degrade a wide variety of biomacromolecules including elastin, and is considered a marker of inflammatory diseases. As the logical strategy to protect tissue is to inhibit excessive elastase activity, experimental and clinical researches have concentrated on trying to find efficient elastase inhibitors. As thymol, one of the major components of thyme oil with a phenolic structure, has been credited with a series of pharmacological properties, that include antimicrobial and antioxidant effects, the aim of this study was to explore whether it can also interfere with the release of elastase by human neutrophils stimulated with the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). After the neutrophils were incubated with increasing amounts of thymol (2.5, 5, 10, 20 microg/ml), elastase release was initiated by fMLP and measured using MeO-Suc-Ala-Ala-Pro-Val-MCA. The results showed that thymol inhibited fMLP-induced elastase release in a concentration-dependent manner, with the effects of 10 and 20 microg/ml being statistically significant. The behavior of cytosolic calcium mobilization revealed by fura-2 closely resembled that of elastase, thus suggesting that they may be related. The hydrophobic nature of thymol means that it can approach ion channel proteins through the lipid phase of the membrane, alter the local environment of calcium channels and thus inhibit capacitative calcium entry. In brief, thymol inactivates calcium channels machinery, thus triggering a corresponding reduction in elastase. The antibacterial and antimycotic activity of thymol is already well known, but our findings that it inhibits elastase extend our knowledge of the anti-inflammatory activity of this interesting molecule that is already credited with antioxidant activity. These two latter characteristics make thymol a molecule that can have helpful effects in controlling the inflammatory processes present in many infections.
弹性蛋白酶是一种由活化的人类中性粒细胞释放的丝氨酸蛋白酶，它能降解包括弹性蛋白在内的多种生物大分子，被认为是炎症性疾病的一个标志物。由于保护组织的合理策略是抑制过度的弹性蛋白酶活性，实验和临床研究都集中在试图找到有效的弹性蛋白酶抑制剂上。百里酚是百里香油的主要成分之一，具有酚类结构，具有一系列药理特性，包括抗菌和抗氧化作用。本研究的目的是探讨它是否也能干扰合成趋化肽N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）刺激的人类中性粒细胞释放弹性蛋白酶。在用不同剂量（2.5、5、10、20微克/毫升）的百里酚孵育中性粒细胞后，由fMLP引发弹性蛋白酶释放，并使用甲氧基琥珀酰丙氨酰丙氨酰脯氨酰缬氨酸-甲基香豆素酰胺进行测定。结果表明，百里酚以浓度依赖的方式抑制fMLP诱导的弹性蛋白酶释放，10和20微克/毫升的作用具有统计学意义。用fura-2显示的胞质钙动员行为与弹性蛋白酶的行为非常相似，因此表明它们可能有关联。百里酚的疏水性意味着它可以通过膜的脂质相接近离子通道蛋白，改变钙通道的局部环境，从而抑制钙的容量性内流。简而言之，百里酚使钙通道机制失活，从而引发弹性蛋白酶相应减少。百里酚的抗菌和抗真菌活性已经广为人知，但我们发现它能抑制弹性蛋白酶，这扩展了我们对这种已具有抗氧化活性的有趣分子抗炎活性的认识。后两个特性使百里酚成为一种在控制许多感染中存在的炎症过程方面可能具有有益作用的分子。
