Abstract
Aldose reductase (AR) is an enzyme associated with retinopathy of both type 1 and type 2 diabetic patients. AR is inhibited by giving chemical drugs to prevent diabetic retinopathy, but is associated with deleterious side effects. Compounds isolated from plants are safer than chemical drugs and have a lot of potential. In the present study, three components viz., cinnamaldehyde, cinnamic acid and cinnamyl alcohol derived from the bark of Cinnamomum cassia were used to evaluate their efficiency in inhibiting AR activity. For this, the AR protein structure database was downloaded from PDB and its pictorial database was downloaded from PDBsum. Structural visualization of AR was done by RasMol. Using Q-SiteFinder, prediction of ligand binding site was done. The three dimensional structures of inhibitors viz., cinnamaldehyde, cinnamic acid and cinnamyl alcohol were downloaded from ChemSketch. Docking studies were carried out using ArgusLab software. Docking studies of cinnamaldehyde, cinnamic acid and cinnamyl alcohol against AR was undertaken to gain insight into the binding mode of the investigated compounds at the active site of AR. All compounds were found to be active against AR as indicated by docking results; the best being cinnamaldehyde. Results suggest that cinnamaldehyde, cinnamic acid and cinnamyl alcohol should be evaluated further for therapeutic use in combination with other diabetic drugs. Further, this may be confirmed by drug trials in animal models to find out the optimum dose and its efficiency in inhibiting AR activity to treat diabetic related complications. Keywords: Diabetes, aldose reductase, cinnamon, molecular docking.
Highlights
Diabetic retinopathy is one of the most important complications in both type 1 and type 2 diabetes
Scientists evaluated the role of several proteins that are likely to be involved in diabetic retinopathy by employing multiple sequence alignment using ClustalW tool and constructed a phylogram tree using functional protein sequences extracted from NCBI
It is likely that vascular endothelial growth factor, pro-inflammatory cytokines, advanced glycation end products and adhesion molecules that play a role in diabetic retinopathy may do so by modulating the activity of Aldose reductase (AR)
Summary
Diabetic retinopathy is one of the most important complications in both type 1 and type 2 diabetes. Aldose reductase inhibition (ARI) is ostensibly an ideal target for reducing the deleterious effects associated with polyol pathway activation. ‘Gui zhi’ (dried twig of cinnamon) is collected in spring and summer and dried in the sun or in the shade used in decoctions, has analgesic and anti-pyretic properties This plant species, the commercial source of cinnamon, is important as a spice, but in East Asia is considered to have some medicinal properties, e.g., as a stomachic agent, an antimicrobial agent, an astringent and a carminative agent as pointed out by Namba (1986), Lee and Ahn (1998) and Kim et al (2000). This study would provide a clear understanding on the mode of action of the above mentioned bark-derived components of C. cassia against AR and can be used as an AR inhibitory drug to reduce diabetic related complications
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