Department of Zoology, Osmania University, Hyderabad 500 007, India.
National Institute of Nutrition, Hyderabad 500 007, India.
Chem Biol Interact. 2015 Jul 25;237:18-24. doi: 10.1016/j.cbi.2015.05.010. Epub 2015 May 15.
Increased aldose reductase activity has been implicated in the development of retinopathy due to accumulation of intracellular sugar alcohol, i.e., sorbitol. In this study, the compounds isolated from the Caesalpinia pulcherrima, have been examined for its inhibitory effects on aldose reductase (AR), which plays a major role in diabetic retinopathy. 3,6,7,4',5'-Pentamethoxy-5,3'-dihydroxyflavone (Compound 2) has shown significant inhibition of rat retina AR with an IC50 value of 16.24±0.046μM in a non-competitive manner. Molecular docking study results are steady with the pattern of AR inhibition by Compound 2 and its specificity. The supplementation of Compound 2 suppresses sorbitol accumulation in retina by decreased AR activity in STZ induced diabetic rat in dose dependent manner. Besides this, rats fed with Compound 2 have shown improved levels of antioxidant enzymes. This study revealed that Compound 2 has pharmacologically active component with a potential to inhibit rat retina AR and affecting the delaying process of diabetic retinopathy in STZ induced diabetic rats.
醛糖还原酶活性的增加与细胞内糖醇(如山梨醇)的积累有关,这被认为是导致视网膜病变的原因。在这项研究中,从美丽决明子中分离得到的化合物,因其对醛糖还原酶(AR)的抑制作用而被检测,醛糖还原酶在糖尿病性视网膜病变中起着主要作用。3,6,7,4',5'-五甲氧基-5,3'-二羟基黄酮(化合物 2)以非竞争性方式显示出对大鼠视网膜 AR 的显著抑制作用,IC50 值为 16.24±0.046μM。分子对接研究结果与化合物 2 对 AR 抑制的模式及其特异性一致。补充化合物 2 以剂量依赖的方式抑制 STZ 诱导的糖尿病大鼠视网膜中 AR 活性,从而抑制山梨醇的积累。此外,用化合物 2 喂养的大鼠显示出抗氧化酶水平的提高。这项研究表明,化合物 2 具有药理活性成分,具有抑制大鼠视网膜 AR 的潜力,并影响 STZ 诱导的糖尿病大鼠糖尿病性视网膜病变的延迟过程。