Abstract

Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase (AR). Hence, AR inhibitors are considered as potential agents in the management of diabetic cataract. This study explored the AR inhibition potential of Hemidesmus indicus var. pubescens root extract by in silico and ex vivo methods. Molecular docking studies (Auto Dock tool) between β-sitosterol, hemidesminine, hemidesmin-1, hemidesmin-2, and AR showed that β-sitosterol (− 10.2 kcal/mol) and hemidesmin-2 (− 8.07 kcal/mol) had the strongest affinity to AR enzyme. Ex vivo studies were performed by incubating isolated goat lenses in artificial aqueous humor using galactose (55 mM) as cataract inducing agent at room temperature (pH 7.8) for 72 h. After treatment with Vitamin E acetate − 100 µg/mL (standard) and test extract (500 and 1000 µg/mL) separately, the estimation of biochemical markers showed inhibition of lens AR activity and decreased sorbitol levels. Additionally, extract also normalized the levels of antioxidant markers like SOD, CAT, GSH. Our results showed evidence that H. indicus var. pubescens root was able to prevent cataract by prevention of opacification and formation of polyols that underlines its potential as a possible therapeutic agent against diabetic complications.

Graphic Abstract

中文翻译：

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Hemidesmus indicus var抑制多元醇途径的活性。pubescens R.Br. Linn根提取物，一种醛糖还原酶抑制剂：计算机模拟和体内研究

摘要

糖尿病性白内障的发展主要与通过醛糖还原酶（AR）的作用经由多元醇途径积累的山梨糖醇有关。因此，AR抑制剂被认为是糖尿病性白内障的潜在治疗剂。这项研究探讨了印度半翅目变种的AR抑制潜力。耻骨通过计算机和离体方法提取根提取物。β-谷甾醇，hemideminine，hemidesmin-1，hemidesmin-2和AR之间的分子对接研究（Auto Dock工具）显示，β-谷甾醇（− 10.2 kcal / mol）和hemidesmin-2（− 8.07 kcal / mol）具有对AR酶最强的亲和力。通过在室温（pH 7.8）下用半乳糖（55 mM）作为白内障诱导剂在人工房水中孵育分离的山羊晶状体进行离体研究72小时。分别用醋酸维生素E-100 µg / mL（标准）和测试提取物（500和1000 µg / mL）处理后，对生化标志物的估计显示出对晶状体AR活性的抑制作用和山梨醇水平的降低。此外，提取物还可以使抗氧化剂标记物（如SOD，CAT，GSH）的含量正常化。我们的结果表明，印度H. indicus变种 pubescens根能够通过预防混浊和形成多元醇来预防白内障，这突出了其作为抗糖尿病并发症的可能治疗剂的潜力。

图形摘要