Khellin Exhibits Diuretic and Anti-Urolithiatic Activity in Calcium Oxalate-Induced Urolithiasis in Rats
摘要
Khellin, a major furanochrome found in Ammi visnaga L. (Apiaceae family), has traditional uses in Middle Eastern countries for its diuretic properties and in treating renal colic associated with kidney stones. The purpose of this investigation was to evaluate the anti-urolithiatic activity of Khellin by investigating its diuretic and antioxidant properties.
MethodsIn-silico molecular docking studies were used to explore the binding affinity of Khellin with glycolate oxidase. Diuretic effects were tested using the Lipschitz model in Wistar rats, and urinary ion levels of Na+, K+, and Cl − were measured. Ethylene glycol-induced urolithic rats were treated prophylactically and therapeutically with Khellin. At the end of treatment, urinary stone promoters and inhibitors, renal antioxidant markers (Catalase, Superoxide dismutase, reduced Glutathione), liver glycolate oxidase (GO), and Lactate dehydrogenase (LDH) activity, and renal histopathology were evaluated.
ResultsMolecular docking revealed a significant binding affinity of Khellin to GO, with a binding energy of -8.4 kcal/mol, surpassing the co-crystallized ligand. Prophylactic treatment of Khellin significantly reduced urinary CaOx markers, increased magnesium and citrate excretion, and improved renal architecture by reducing CaOx crystal deposition. Antioxidant defenses were enhanced by increased Catalase, Superoxide dismutase, and reduced Glutathione levels, with decreased lipid peroxidation. Khellin also modulated GO and LDH activity, preventing CaOx crystal formation.
ConclusionKhellin demonstrated significant anti-urolithiatic activity by promoting diuresis, modifying glycolate oxidase, and enhancing antioxidant defenses, supporting the traditional use of Ammi visnaga in managing urolithiasis.