Himalayan Citrus jambhiri juice reduced renal crystallization in nephrolithiasis by possible inhibition of glycolate oxidase and matrix metalloproteinases.

Abstract

Citrus fruits are a very rich source of electrolytes and citric acid. They have been used traditionally for treating urinary ailments and renal stones. Citrus jambhiri is indigenously used as a diuretic. Present study aimed at establishing the antiurolithiatic potential of the juice of Citrus jambhiri fruits along with the elucidation of the mechanism involved in the urolithiasis disease defying activity. The antiurolithiatic activity was established by means of nucleation, growth and aggregation assay in the in vitro settings and by means of ethylene glycol mediated calcium oxalate urolithiasis in the male Wistar rats. Docking studies were performed in an attempt to determine the mechanism of the antiurolithiatic action. Present study revealed the role of C. jambhiri fruit juice in reducing nucleation, growth and aggregation of calcium oxalate crystals by possible reduction in the urinary supersaturation relative to calcium oxalate and raising the zeta potential of the calcium oxalate crystals. C. jambhiri fruit juice treatment in experimental rats produced significant amelioration of hypercalciuria, hyperoxaluria, hyperphosphaturia, hyperproteinuria, hyperuricosuria, hypocitraturia and hypomagnesiuria and ion activity product of calcium oxalate. It exhibited nephroprotection against calcium oxalate crystals induced renal tubular dilation and renal tissue deterioration. Docking studies further revealed high binding potential of the phytoconstituents of C. jambhiri viz. narirutin, neohesperidin, hesperidin, rutin and citric acid with glycolate oxidase and matrix metalloproteinase-9. C. jambhiri fruit juice possesses excellent antiurolithiatic activity. The study reveals antiurolithiatic mechanism that involves restoration of equilibrium between the promoters and inhibitors of stone formation; and inhibition of matrix metalloproteinases and glycolate oxidase.