Department of Neurology, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.
Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
Metab Brain Dis. 2017 Dec;32(6):1855-1860. doi: 10.1007/s11011-017-0078-1. Epub 2017 Jul 26.
Elevated plasma homocysteine (2-amino-4-sulfanylbutanoic acid) level is a risk factor for stroke. Moreover, it has been suggested that high levels of homocysteine in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype. In clinical studies, supplementation with genistein (5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one) decreased plasma homocysteine levels considerably. Therefore, genistein could be considered as a potential drug for prevention and/or treatment of stroke. However, the mechanism of the effect of genistein on homocysteine level remains to be elucidated. In this report, direct functional interactions between homocysteine and genistein are demonstrated in in vitro experimental systems for determination of methylenetetrahydrofolate reductase (MetF) and glutathione peroxidase (GPx) activities, reconstructed with purified compounds, and in a simple in vivo system, based on measurement of growth rate of Vibrio harveyi and Bacillus subtilis cultures. Results of molecular modelling indicated that homocysteine can directly interact with genistein. Therefore, genistein-mediated decrease in plasma levels of homocysteine, and alleviation of biochemical and physiological effects of one of these compounds by another, might be ascribed to formation of homocysteine-genistein complexes in which biological activities of these molecules are abolished or alleviated.
血浆同型半胱氨酸（2-氨基-4-巯基丁酸）水平升高是中风的危险因素。此外，有研究表明，缺血性中风急性期同型半胱氨酸水平升高可预测死亡率，尤其是大血管粥样硬化亚型的中风患者。在临床研究中，补充染料木黄酮（5,7-二羟基-3-（4-羟基苯基）-4H-1-苯并吡喃-4-酮）可显著降低血浆同型半胱氨酸水平。因此，染料木黄酮可以被认为是预防和/或治疗中风的潜在药物。然而，染料木黄酮对同型半胱氨酸水平影响的机制仍有待阐明。在本报告中，通过使用纯化化合物重建的体外实验系统，以及基于测量哈维弧菌和枯草芽孢杆菌培养物的生长速率的简单体内系统，直接证明了同型半胱氨酸与染料木黄酮之间的直接功能相互作用，以确定亚甲基四氢叶酸还原酶（MetF）和谷胱甘肽过氧化物酶（GPx）的活性。分子建模结果表明，同型半胱氨酸可以直接与染料木黄酮相互作用。因此，染料木黄酮介导的血浆同型半胱氨酸水平降低，以及另一种化合物缓解这些化合物的生化和生理作用，可能归因于同型半胱氨酸-染料木黄酮复合物的形成，其中这些分子的生物学活性被消除或缓解。
