Abstract Context: Nephrotoxicity is a renal dysfunction that arises from direct exposure to environmental chemicals or as a side effect of therapeutic drugs. Boerhaavia diffusa Linn. (Nyctaginaceae), Rheum emodi Wall. Ex. Meissn. (Polygonaceae), Nelumbo nucifera Gaertn. (Nelumbonaceae) and Crataeva nurvala Buch-Ham. (Capparidaceae) are well-recognized medicinal plants of Indian traditional system of medicine used for kidney disorders. Objectives: The present investigation was undertaken to develop a chromatographically characterized polyherbal combination and to evaluate its nephroprotective activity. Materials and methods: Roots of B. diffusa and R. emodi, flowers of N. nucifera and stem bark of C. nurvala 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. Results: 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 (p ≤ 0.05) DPPH scavenging potential and xanthine oxidase inhibition. The half maximal inhibitory concentration (IC50) 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 (p ≤ 0.05) improved the kidney function markers, oxidative stress markers and histological parameters. Discussion and conclusion: 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.

中文翻译：

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标准化多草药组合对甲氨蝶呤诱导的大鼠肾毒性的改善作用

摘要背景：肾毒性是由直接暴露于环境化学物质或作为治疗药物的副作用引起的肾功能障碍。Boerhaavia diffusa Linn。(Nyctaginaceae), Rheum emodi Wall。前任。迈森。（蓼科），Nelumbo nucifera Gaertn。(Nelumbonaceae) 和 Crataeva nurvala Buch-Ham。（Capparidaceae）是印度传统医学系统中公认的用于治疗肾脏疾病的药用植物。目的：本研究旨在开发一种色谱表征的多草药组合并评估其肾保护活性。材料与方法：白花蛇舌草根、白花蛇舌草的花和白花蛇舌草的茎皮用70%乙醇水煎提取。响应面法 (RSM) 用于优化提取参数。在 Wistar 大鼠中测试了不同剂量 (150–300 mg/kg) 的多药组合对甲氨蝶呤诱导的肾毒性。结果：优化的提取物含有 27% 的酚类和 15% 的黄酮类化合物，显示 75% 的 1, 1-二苯基-2-苦基-肼 (DPPH) 清除潜力。根据高效液相色谱 (HPLC) 分析的保留时间，发现 122 种成分中有 17 种在所有提取物和组合中都很常见。两种组合显示出显着更高的 (p ≤ 0.05) DPPH 清除能力和黄嘌呤氧化酶抑制作用。DPPH 清除和黄嘌呤氧化酶抑制的最佳组合的半数最大抑制浓度 (IC50) 分别为 80 和 74 µg/mL。多药联合治疗甲氨蝶呤诱导的肾毒性大鼠显着（p ≤ 0. 05) 改善肾功能标志物、氧化应激标志物和组织学参数。讨论和结论：发现开发的组合对肾毒性有效；可以进一步探索它用于治疗药物引起的肾毒性和其他慢性肾脏疾病。