Repression of Polyol Pathway Activity by Hemidesmus indicus var. pubescens R.Br. Linn Root Extract, an Aldose Reductase Inhibitor: An In Silico and Ex Vivo Study

Natural Products and Bioprospecting

Vijaybhanu Perumalsamy¹  Joel Monichen¹  Kanchan Prabha²  Rajitha Kolli³  Dhanusha Koppal Anand³  Gouri Nair³  Hajira Banu Haroon³ 

[1] Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Gnanagangothri Campus, New BEL Road, 560054, Bengaluru, Karnataka, India;Department of Pharmaceutics, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Gnanagangothri Campus, New BEL Road, 560054, Bengaluru, Karnataka, India;Department of Pharmacology, Faculty of Pharmacy, M S Ramaiah University of Applied Sciences, Gnanagangothri Campus, New BEL Road, 560054, Bengaluru, Karnataka, India;

关键词: Hemidesmus indicus;    Aldose reductase;    Polyol pathway;    Diabetic cataract;   

DOI  :  10.1007/s13659-020-00290-w

来源: Springer

【 摘 要 】

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

【 授权许可】

CC BY