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

Hajira Banu Haroon,Joel Monichen,Dhanusha Koppal Anand,Rajitha Kolli,Vijaybhanu Perumalsamy,Kanchan Prabha,Gouri Nair

doi:10.1007/s13659-020-00290-w

Hajira Banu Haroon, Joel Monichen + Show 5 more

Open Access

https://doi.org/10.1007/s13659-020-00290-w

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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

Highlights

Cataract has become one of the leading causes of visual impairment and blindness worldwide and diabetes mellitus is considered to be one of the major risk factors
It is suggested that hyperglycemia activates Aldose reductase (AR) and eventually polyol pathway that leads to increased build-up of sorbitol in the cell causing oxidative stress and loss of cellular proteins leading to cataract [14]
The present study demonstrates the AR inhibitory activity of H. indicus var. pubescens and its anticataract potential

Summary

Introduction

Cataract has become one of the leading causes of visual impairment and blindness worldwide and diabetes mellitus is considered to be one of the major risk factors. A cataract is the opacification or optical dysfunction of the crystalline lens, associated with the breakdown of the eye lens micro-architecture, which interferes with the transmission of light onto the retina [1]. In Diabetes Mellitus, the cellular levels of glucose greatly increase in tissues where glucose entry is independent of insulin, like the lens, retina, kidney, and peripheral nerves. Due to this extra pressure on the lens, it becomes inflexible and this damages cells to the point of cataract formation. Hyperglycemia or sustained increase of blood glucose contributes to cataract formation in three ways viz., non-enzymatic glycation of eye lens proteins, activated polyol pathway in glucose disposition, and oxidative stress [2]

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