Alim Zuhal, Kilinç Namik, Şengül Bülent, Beydemir Şükrü
a Department of Chemistry, Faculty of Science and Arts , Ahi Evran University , Kirşehir , Turkey.
b Department of Medical Services and Techniques, Vocational School of Health Service , Iğdir University , Iğdir , Turkey.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):277-284. doi: 10.1080/14756366.2016.1250752.
Aldose reductase (AR) inhibitors have vital importance in the treatment and prevention of diabetic complications. In this study, rat kidney AR was purified 19.34-fold with a yield of 3.49% and a specific activity of 0.88 U/mg using DE-52 Cellulose anion exchange chromatography, gel filtration chromatography and 2'5' ADP Sepharose-4B affinity chromatography, respectively. After purification, the in vitro inhibition effects of some phenolic acids (tannic acid, chlorogenic acid, sinapic acid, protocatechuic acid, 4-hydroxybenzoic acid, p-coumaric acid, ferulic acid, vanillic acid, syringic acid, α-resorcylic acid, 3-hydroxybenzoic acid and gallic acid) were investigated on purified enzyme. We determined IC, K values and inhibition types of these phenolic acids. As a result, tannic and chlorogenic acid had a strong inhibition effect. On the other hand, gallic acid had a weak inhibition effect. In this study, all phenolic acids except for chlorogenic acid and p-coumaric acid showed non-competitive inhibition effects on rat kidney AR.
醛糖还原酶(AR)抑制剂在糖尿病并发症的治疗和预防中具有至关重要的意义。在本研究中,分别使用DE-52纤维素阴离子交换色谱、凝胶过滤色谱和2'5' ADP琼脂糖-4B亲和色谱,将大鼠肾脏AR纯化了19.34倍,产率为3.49%,比活性为0.88 U/mg。纯化后,研究了一些酚酸(鞣酸、绿原酸、芥子酸、原儿茶酸、4-羟基苯甲酸、对香豆酸、阿魏酸、香草酸、丁香酸、α-间苯二酚、3-羟基苯甲酸和没食子酸)对纯化酶的体外抑制作用。我们测定了这些酚酸的IC、K值和抑制类型。结果,鞣酸和绿原酸具有较强的抑制作用。另一方面,没食子酸具有较弱的抑制作用。在本研究中,除绿原酸和对香豆酸外,所有酚酸对大鼠肾脏AR均表现出非竞争性抑制作用。