Ameliorative effect of a standardized polyherbal combination in methotrexate-induced nephrotoxicity in the rat.

Nephrotoxicity is a renal dysfunction that arises from direct exposure to environmental chemicals or as a side effect of therapeutic drugs. Linn. (Nyctaginaceae), Wall. Ex. Meissn. (Polygonaceae), Gaertn. (Nelumbonaceae) and Buch-Ham. (Capparidaceae) are well-recognized medicinal plants of Indian traditional system of medicine used for kidney disorders. The present investigation was undertaken to develop a chromatographically characterized polyherbal combination and to evaluate its nephroprotective activity. Roots of and , flowers of and stem bark of were extracted by decoction using 70% ethanol. Response surface methodology (RSM) was used for the optimization of extraction parameters. Polyherbal combinations with different doses (150-300 mg/kg) were tested against methotrexate-induced nephrotoxicity in Wistar rats. The optimized extract contained 27% phenols and 15% flavonoids, which showed 75% 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging potential. Based on the retention time of high-performance liquid chromatography (HPLC) analysis, 17 out of 122 constituents were found common in all extracts and combinations. Two combinations showed significantly higher ( ≤ 0.05) DPPH scavenging potential and xanthine oxidase inhibition. The half maximal inhibitory concentration (IC) of the best combination for DPPH scavenging and xanthine oxidase inhibition were 80 and 74 µg/mL, respectively. Treatment of methotrexate-induced nephrotoxic rats with polyherbal combination significantly ( ≤ 0.05) improved the kidney function markers, oxidative stress markers and histological parameters. The developed combination was found to be effective in nephrotoxicity; it can be explored further for the management of drug-induced nephrotoxicity and other chronic kidney diseases.