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

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

Current Approach to the Pathogenesis of Diabetic Cataracts

“…Initially, the energy-dependent lens pumps are capable of compensating for this but, eventually, become overloaded. This results in liquefaction and swelling of the lens fibers, leading to their degeneration and opacification [ 41 , 42 ]. This process is of particular relevance in young patients with type 1 diabetes [ 43 , 44 ] due to extensive edema of the cortical lens fibers [ 45 ].…”

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives

“…They found that 100 and 200 mg ethyl acetate treatment will lead to decrease in malondialdehyde and increase in the inorganic phosphorous content ( Kota et al, 2017 ). Phytomolecules like quercetin ( Lan et al, 2020 ), chlorogenic acid ( Kim et al, 2011 ), and β-sitosterol ( Haroon et al, 2020 ) may be responsible for this anticataract property of Alternanthera sessilis (L.) R.Br. ex DC.…”

Association of Alpha-Crystallin with Human Cortical and Nuclear Lens Lipid Membrane Increases with the Grade of Cortical and Nuclear Cataract

“…This increased oxidative stress and loss of antioxidants consequentially creates the oxidative environment inside the lens, promoting lipid peroxidation, which likely pushes Chol out of the lens membrane, reducing the lens Chol content, diminishing the amount and size of CBDs, and consequentially allowing for increased α-crystallin lens membrane binding. Moreover, dysregulation of the sorbitol pathway can result in fluid accumulation within the lens that causes liquefication and degeneration of the lens fibers [95,98,99]. Separate from the sorbitol pathway, there has also shown to be increased expression of pro-inflammatory cytokines within the lens of diabetic patients that is believed to possibly cause cellular dysfunction and apoptosis [103,104,137].…”