In-Silico Analysis of Selected Bioactive Compounds Present in Siddha Formulation Nanthiyavarthathi Pizhi Marunthu Against Kan Kasam (Cataract) Activity

Background
Cataract is one of the leading causes of blindness globally. The enzyme aldose reductase plays a critical role in cataract genesis by catalyzing the reduction of glucose into sorbitol, resulting in osmotic stress and lens epithelial cell apoptosis. Inhibition of this enzyme can delay sorbitol accumulation and prevent or slow cataract development. Nanthiyavarthathi Pizhi Marunthu, a Siddha formulation, contains several bioactive phytocomponents with potential aldose reductase inhibitory activity.
Methodology
Ten phytocomponents Voacristine, Lupeol, Moringin, Kaempferol, Rutin, β-sitosterol, Adhatodine, Vasicoline, Anisotine, and Gallic acid were retrieved and subjected to molecular docking against human aldose reductase enzyme (PDB ID: 4GCA) using Auto Dock tools. Epalrestat was used as the standard drug.
Results
All selected phytocomponents exhibited good binding affinity with the active site residues of the aldose reductase enzyme. Rutin (−13.09 kcal/mol; Ki 254.51 pM), β-sitosterol (−12.07 kcal/mol; Ki 1.41 nM), and Anisotine (−10.77 kcal/mol; Ki 12.84 nM) showed the strongest binding energies. The interaction profiles of these compounds were comparable or superior to Epalrestat (−9.90 kcal/mol; Ki 55.17 nM), demonstrating multiple hydrogen bonds with critical amino acid residues.
Conclusion
The molecular docking analysis reveals that the phytocomponents of Nanthiyavarthathi Pizhi Marunthu possess strong inhibitory potential against aldose reductase. These compounds may reduce sorbitol accumulation, thereby delaying cataract progression. The findings provide a scientific basis for the traditional use of this Siddha formulation and identify promising lead molecules for further pharmacological and clinical investigations in cataract prevention.

Kan kasam, Cataract, Nanthiyavarthathi Pizhi Marunthu, Epalrestat

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