Fructus Psoraleae (FP) is commonly used in the treatment of vitiligo, osteoporosis, and other diseases in clinic. As a result, the toxicity caused by FP is frequently encountered in clinical practice; however, the underlying toxicity mechanism remains unclear. The purpose of this study was to investigate the toxic effect of the ethanol extract of FP (EEFP) in rats and to explore the underlying toxic mechanisms using a metabolomics approach. The toxicity was evaluated by hematological indicators, biochemical indicators, and histological changes. In addition, a serum metabolomic method based on ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight MS (UPLC–Q‐TOF–MS) had been established to investigate the hepatorenal toxicity of FP. Multivariate statistical approaches, such as partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, were built to evaluate the toxic effects of FP and find potential biomarkers and metabolic pathways. Ten endogenous metabolites had been identified and the related metabolic pathways were involved in phospholipid metabolism, amino acid metabolism, purine metabolism, and antioxidant system activities. The results showed that long‐term exposure to high‐dose EEFP may cause hepatorenal toxicity in rats. Therefore, serum metabolomics can improve the diagnostic efficiency of FP toxicity and make it more accurate and comprehensive.

中文翻译：

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乌骨菜乙醇提取物对Sprague Dawley大鼠的肝毒性和肾毒性的UPLC-Q-TOF-MS血清代谢组学分析

补骨脂（FP）通常用于临床治疗白癜风，骨质疏松和其他疾病。结果，由FP引起的毒性在临床实践中经常遇到。然而，潜在的毒性机制仍不清楚。这项研究的目的是调查FP乙醇提取物（EEFP）在大鼠中的毒性作用，并使用代谢组学方法探讨其潜在的毒性机制。通过血液学指标，生化指标和组织学变化评估毒性。此外，已经建立了一种基于超高效液相色谱结合四极杆飞行时间质谱（UPLC-Q-TOF-MS）的血清代谢组学方法，以研究FP的肝肾毒性。多元统计方法，例如偏最小二乘判别分析和正交偏最小二乘判别分析，旨在评估FP的毒性作用并发现潜在的生物标志物和代谢途径。已鉴定出十种内源性代谢物，相关的代谢途径涉及磷脂代谢，氨基酸代谢，嘌呤代谢和抗氧化系统活性。结果表明，长期暴露于大剂量EEFP可能会引起大鼠肝肾毒性。因此，血清代谢组学可以提高FP毒性的诊断效率，使其更加准确和全面。已鉴定出十种内源性代谢物，相关的代谢途径涉及磷脂代谢，氨基酸代谢，嘌呤代谢和抗氧化系统活性。结果表明，长期暴露于大剂量EEFP可能会引起大鼠肝肾毒性。因此，血清代谢组学可以提高FP毒性的诊断效率，使其更加准确和全面。已鉴定出十种内源性代谢物，相关的代谢途径涉及磷脂代谢，氨基酸代谢，嘌呤代谢和抗氧化系统活性。结果表明，长期暴露于大剂量EEFP可能会引起大鼠肝肾毒性。因此，血清代谢组学可以提高FP毒性的诊断效率，使其更加准确和全面。