Studies on the in vitro and in vivo antiurolithic activity of Holarrhena antidysenterica

Holarrhena antidysenterica has a traditional use in the treatment of urolithiasis, therefore, its crude extract has been investigated for possible antiurolithic effect. The crude aqueous-methanolic extract of Holarrhena antidysenterica (Ha.Cr) was studied using the in vitro and in vivo methods. In the in vitro experiments, Ha.Cr demonstrated a concentration-dependent (0.25-4 mg/ml) inhibitory effect on the slope of aggregation. It decreased the size of crystals and transformed the calcium oxalate monohydrate (COM) to calcium oxalate dehydrate (COD) crystals, in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and lipid peroxidation induced in rat kidney tissue homogenate. Ha.Cr (0.3 mg/ml) reduced (p < 0.05) the cell toxicity and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 mu g/cm(2)) crystals. In male Wistar rats, receiving 0.75 % ethylene glycol (EG) for 21 days along with 1 % ammonium chloride (AC) in drinking water, Ha.Cr treatment (30-100 mg/kg) prevented the toxic changes caused by lithogenic agents; EG and AC, like loss of body weight, polyurea, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls. These data indicate that Holarrhena antidysenterica possesses antiurolithic activity, possibly mediated through the inhibition of CaOx crystal aggregation, antioxidant and renal epithelial cell protective activities and may provide base for designing future studies to establish its efficacy and safety for clinical use.