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The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS

机译:基于UPLC-Q-TOF / MS的非靶向代谢组学方法评价P草对大鼠的毒性

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摘要

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.
机译:补骨脂是豆科植物Psoralea corylifolia L.的干燥成熟果实,具有温暖肾脏,增强阳气,健脾等功效。但是,大剂量会引起肝肾毒性。因此,有必要系统评价evaluate药的毒性。尽管传统的生化指标和病理学检查方法已被用于评估药物的安全性,但是这些方法缺乏敏感性和特异性,因此迫切需要一种快速灵敏的分析方法。在这项研究中,超高效液相色谱结合四极杆飞行时间质谱(UPLC-Q-TOF / MS)方法用于分析大鼠血浆的代谢谱。通过偏最小二乘判别分析(PLS-DA)检测血浆样品中代谢物的变化。与对照组相比,给药7天后,病理切片显示肝肾毒性,代谢趋势发生改变。最终,筛选了与potential草毒性相关的13种潜在生物标记。涉及的代谢途径是甘油磷脂代谢,氨基酸代谢,能量代谢等。这些生物标志物的发现为更好地解释s骨的肝毒性和肾毒性奠定了基础,并为其安全性评估提供了保证。

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