Molecular Docking Analysis of Thirikandagathi Kiyaazham Against Tamm–Horsfall Protein for Anti-Urolithiatic Activity

Abstract

Urolithiasis is a common renal disorder characterized by the formation and aggregation of urinary crystals.  Tamm- Horsfall protein (THP) plays a crucial role in modulating crystal nucleation and aggregation. This study evaluates the anti-urolithiatic potential of phytocompounds derived from a Siddha herbal decoction, Thirikandagathi kiyaazham (TKK) Objective: To identify and characterize phytocomponents from the Siddha formulation TKK that can bind to the Tamm–Horsfall protein (PDB-4WRN) and inhibit calcium oxalate crystallization. Methods: Seven phytocompounds were selected from TKK-Terminalia Chebula (gallic acid, maslinic acid), Emblica officinalis (ellagic acid, lupeol, quercetin), and Aerva lanata (rutin, ferulic acid)- and subjected to molecular docking analysis. Docking simulations were performed using auto dock tools with the Lamarckian genetic algorithm, focusing on interactions with core active-site residues (Cys527, Pro528, His529, Gly534, Arg583, Thr585, and Arg586) of the target protein. Results: Maslinic acid demonstrated the strongest interaction, forming contacts with three core residues (Cys527, Pro528, and Gly534), while ellagic acid and quercetin showed moderate interactions with two residues (Cys527 and Pro528). Gallic acid, lupeol, and ferulic acid exhibited limited interactions with single core residues, whereas rutin did not interact with any defined core active-site residues. Conclusion: Phytocompounds from TKK demonstrating multiple interactions with THP residues shows potential inhibition of calcium oxalate crystallization, suggesting their therapeutic profile for urolithiasis management and prevention of renal complications.