Evaluation of invivo anti-lithiatic activity of polyherbal formulation in ameliorating calcium oxalate kidney stones and integrated invitro-insilico studies

Abstract

The present study validates invivo anti-lithiatic activity of a polyherbal formulation (URO-5) on calcium oxalate (CaOx) stones. The effect of URO-5 on CaOx crystallization was tested invitro and Insilico molecular docking was conducted to explore the mechanism of action. Invitro studies showed that URO-5 drastically reduces the number of CaOx crystals and facilitate the efflux due to alteration in their morphology. It promotes the formation of dihydrate type of crystals. The inhibition (IC₅₀) of crystal nucleation and aggregation at low concentration of 4.51 and 11.17 mg/ml suggests antagonistic action on crystallization. URO-5 characterized through high performance liquid chromatography showed the presence of eight bioactive metabolites and insilico data suggest that anti-lithiatic activity of URO-5 was mediated via calcium, oxalate, and antioxidant dependent pathways. Invivo activity (500 mg/kg) reveals that CaOx crystals efflux were prominent ( 80 %) in URO-5 and is at par with Cystone®. The decrease in tissue calcium and increase in urine calcium was significant (p > 0.05) at 15.14 and 74.08 μg/mg. Interestingly, URO-5 also repairs the tissue damage caused by CaOx stones and was non-toxic under the tested conditions. In nutshell, URO-5 is a safe and efficacious alternative and can be used as an adjuvant therapy in urolithiasis.