Antiurolithiatic Potential of Ficus racemosa L. Leaf Gall Extract: In Vivo, In Silico, and Histopathological Insights into Calcium Oxalate Nephrolithiasis

Abstract

Background: Urolithiasis, primarily caused by calcium oxalate crystal deposition, remains a recurrent clinical challenge despite available surgical and pharmacological interventions. Traditional Ayurvedic medicine highlights Ficus racemosa L (gular) for renal disorders, yet its leaf galls remain underexplored for antiurolithiatic potential. Objective: To evaluate the preventive and curative efficacy of Ficus racemosa L. leaf gall extract (FRGE) in an ethylene glycol-induced urolithiasis model in Wistar rats, and to explore its mechanistic basis through biochemical, histopathological, and in silico approaches. Methods: Methanolic extracts of authenticated leaf galls were administered orally at graded doses (100, 250, 500 mg/kg) in both preventive (days 1–28) and curative (days 15–28) regimens. Urinary and serum biochemical markers, renal oxidative stress parameters, and histopathological changes were assessed. Molecular docking of major phytoconstituents (quercetin, rutin, catechin, epicatechin) with lithogenic proteins (osteopontin, NF-κB, NADPH oxidase) was performed, alongside ADMET profiling. Results: FRGE significantly normalized urinary calcium, oxalate, phosphate, and uric acid levels, while reducing serum creatinine, uric acid, and blood urea nitrogen. Antioxidant enzyme activities (SOD, CAT, and GSH) were restored, and lipid peroxidation was attenuated. Histopathology confirmed preserved renal architecture and reduced calcium oxalate deposition, particularly at 500 mg/kg. Docking studies revealed strong binding affinities of quercetin and rutin to lithogenic proteins, supporting inhibition of crystal adhesion and oxidative pathways. ADMET analysis indicated favorable pharmacokinetic and safety profiles. Conclusion: FRGE demonstrated significant preventive and curative antiurolithiatic activity, mediated through modulation of urinary biochemistry, oxidative stress, and renal protection. These findings validate its ethnomedicinal use and highlight Ficus racemosa L. leaf galls as a promising natural therapeutic candidate for urolithiasis management.