Pathway-Centric Approach to Urolithiasis Treatment Using Desmostachya Bipinnata Phytochemicals

Abstract

Urolithiasis, the formation of urinary stones, is a prevalent condition that affects millions worldwide, often leading to severe pain, urinary tract infections, and kidney damage. While conventional treatments, including pharmacological agents and surgical interventions, exist, they are associated with side effects and high recurrence rates. Desmostachya bipinnata, a traditionally used medicinal plant, has shown potential in mitigating urolithiasis through its diverse phytochemical composition. This study aims to evaluate its therapeutic efficacy using computational approaches. Leaves of Desmostachya bipinnata were collected, authenticated, and processed for ethanolic extraction. The extract was tested for calcium oxalate crystal inhibition using a nucleation assay. Cytotoxicity was assessed on HK-2 renal epithelial cells using the MTT assay. Computational screening included drug-likeness analysis, pharmacokinetic profiling, and toxicity prediction for 20 phytochemicals, reducing the final selection to 14 compounds. Target prediction was conducted using DIGEP-Pred 2.0, followed by disease-related gene identification through CTD and GeneCards databases. Protein-protein interaction (PPI) analysis was performed using STRING, and functional enrichment was assessed through Gene Ontology (GO) and KEGG pathways. Molecular docking studies were carried out on six urolithiasis-related target proteins, with Desmostachya bipinnata phytochemicals compared to tamsulosin, a standard urolithiasis medication. The nucleation assay demonstrated a dose-dependent inhibition of calcium oxalate crystal formation, with efficacy comparable to Cystone. The MTT assay confirmed the extract’s low cytotoxicity, with cell viability exceeding 84% at the highest tested concentration. Computational analyses identified 71 unique genes linked to Desmostachya bipinnata phytochemicals, with 14 central genes associated with urolithiasis. PPI analysis revealed significant interactions with proteins involved in oxidative stress, inflammation, and metabolic regulation. Molecular docking demonstrated strong binding affinities of selected phytochemicals with key targets such as CCL2, CYP1A1, HMOX1, NQO1, PPARA, and SIRT1, with some interactions comparable or superior to tamsulosin. This study establishes Desmostachya bipinnata as a promising natural therapeutic agent for urolithiasis, exhibiting multi-target activity through interactions with key proteins involved in stone formation and renal dysfunction. Its phytochemicals demonstrated comparable or superior molecular docking scores to tamsulosin, suggesting its potential as a natural alternative or adjunct therapy. Further in vivo studies are required to validate these computational findings, focusing on its efficacy in preventing stone formation and modulating renal oxidative stress and inflammation. Future research should also explore nanoformulation-based drug delivery systems to enhance bioavailability and clinical translation.