Hartmann Anja, Gostner Johanna, Fuchs Julian E, Chaita Eliza, Aligiannis Nektarios, Skaltsounis Leandros, Ganzera Markus
Institute of Pharmacy, Pharmacognosy, University of Innsbruck, Innsbruck, Austria.
Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Planta Med. 2015 Jul;81(10):813-20. doi: 10.1055/s-0035-1546105. Epub 2015 Jun 3.
Matrix metalloproteinases play an important role in extracellular matrix remodeling. Excessive activity of these enzymes can be induced by UV light and leads to skin damage, a process known as photoaging. In this study, we investigated the collagenase inhibition potential of mycosporine-like amino acids, compounds that have been isolated from marine organisms and are known photoprotectants against UV-A and UV-B. For this purpose, the commonly used collagenase assay was optimized and for the first time validated in terms of relationships between enzyme-substrate concentrations, temperature, incubation time, and enzyme stability. Three compounds were isolated from the marine red algae Porphyra sp. and Palmaria palmata, and evaluated for their inhibitory properties against Chlostridium histolyticum collagenase. A dose-dependent, but very moderate, inhibition was observed for all substances and IC50 values of 104.0 µM for shinorine, 105.9 µM for porphyra, and 158.9 µM for palythine were determined. Additionally, computer-aided docking models suggested that the mycosporine-like amino acids binding to the active site of the enzyme is a competitive inhibition.
基质金属蛋白酶在细胞外基质重塑中起重要作用。这些酶的过度活性可由紫外线诱导，并导致皮肤损伤，这一过程称为光老化。在本研究中，我们研究了类菌孢素氨基酸对胶原酶的抑制潜力，这类化合物是从海洋生物中分离出来的，已知是抗UV-A和UV-B的光保护剂。为此，对常用的胶原酶测定法进行了优化，并首次在酶-底物浓度、温度、孵育时间和酶稳定性之间的关系方面进行了验证。从海洋红藻紫菜属和掌状红皮藻中分离出三种化合物，并评估了它们对溶组织梭菌胶原酶的抑制特性。观察到所有物质均呈剂量依赖性但非常适度的抑制作用，分别测定了 shinorine 的 IC50 值为 104.0 μM、紫菜的 IC50 值为 105.9 μM 和 palythine 的 IC50 值为 158.9 μM。此外，计算机辅助对接模型表明，类菌孢素氨基酸与酶活性位点的结合是一种竞争性抑制。
