ADMET Assessment, Molecular Docking, and In Vitro Antioxidant and Anti-urolithiatic Activities of Natural Furanochrome Khellin

Abstract

Urolithiasis is characterized by the formation of urinary calculi and poses a significant health concern due to its associated symptoms and recurrence rates. This study focuses on exploring the phytoconstituents responsible for the anti-urolithic activity of traditionally used Ammi visnaga fruits in preventing kidney stones by utilizing various databases and software tools to predict their targets. The small molecules were retrieved from the IMPPAT database and screened for pharmacokinetic attributes, toxicity prediction, and docking analyses using SwissADME, Protox-II, and Autodock Vina. This comprehensive approach identified five key compounds-khellinol, khellin, visamminol, khellol, and visnagin for their drug-like characteristics and interaction potential with target proteins involved in oxidative stress pathways. Further, in vitro assays were conducted to evaluate the antioxidant and anti-urolithiatic activity of khellin, revealing significant IC50 values of 67.39 μg, 36.44 μg, and 134.94 μg for DPPH, hydrogen peroxide scavenging, and superoxide radical scavenging assays, respectively. Additionally, khellin inhibited the oxidation of glutathione by preserving 68.7% of its sulfhydryl groups at a concentration of 200 μg. Concentration-dependent responses were observed in nucleation, aggregation, and growth assays of anti-urolithiatic activity. Notably, khellin demonstrated significant antioxidant effects and inhibition of crystal formation, presenting itself as a potential candidate responsible for preventing urolithiasis. The current study emphasizes the promising role of Ammi visnaga fruit phytoconstituents, particularly khellin, as a prospective avenue for managing kidney stone formation, further comprehensive in vivo studies are warranted to validate these outcomes and efficacy under physiological conditions.