大戟 (EP) 以其利尿特性而闻名，临床上用于治疗水肿和恶性肿瘤等疾病。但生的大戟有毒，口服这种生药会刺激胃肠道，导致腹痛、腹泻。蒙药民族药体系中，采用了一种独特的炮制方法，称为“车布拉果炮制”。 Chebulae Fructus 用于减轻 EP 的毒性并减轻其泻药作用。然而，与这种加工方法相关的解毒机制仍有待探索。推测，乌龟炮制可能会改变EP的化学成分，而炮制中药中乌龟残留成分可能会表现出药理拮抗作用，从而达到炮制减毒的目的。为了进一步研究这一点，采用基于 UPLC-QTOF-MS 的代谢组学技术和多变量统计分析相结合来分析和比较原始和加工后的 EP 的化学成分。根据特定标准确定导致组分离的差异变量，包括 PLS-DA 模型中 VIP（投影中的变量重要性）值 ≥ 1、p 值 < 0.05 以及倍数变化 (FC) > 1.2 或 < 0.8。然后通过数据库匹配、文献综述或手动注释来识别所得的差异表达特征。在正电离和负电离模式下，从 PEP 样品中总共鉴定出 47 种成分，主要属于黄酮类、萜类、有机酸、糖苷和脂肪酸。在原始 EP 组和 PEPS S4 组中，鉴定出 10 种差异化合物。值得注意的是，加工组中EP中的一种有毒萜烯和一种苯丙素含量下调，而Chebulae Fructus中的两种生物活性成分含量上调。还阐明了这两个加工 Q 标记的可能转化反应。采用车厘子的特色炮制，使这款蒙药EP的成分发生了变化。此外，本研究为优化 EP 加工技术提供了科学基础，并为其他具有毒性的民族药物的加工提供了见解。版权所有 © 2023 Elsevier B.V. 保留所有权利。

Euphorbia pekinensis (EP), known for its diuretic properties, is clinically utilized for treating conditions such as edema and malignant tumors. However, in its raw form, Euphorbia pekinensis is toxic, and oral administration of this crude medicine can lead to gastrointestinal stimulation, resulting in abdominal pain and diarrhea. In Mongolian medicine's ethnomedicinal system, a distinctive processing method called "Chebulae Fructus processing" is employed. Chebulae Fructus is used to mitigate the toxicity of EP and alleviate its purgative effects. Nevertheless, the detoxification mechanism associated with this processing method remains unexplored. It is hypothesized that processing with Chebulae Fructus may alter the chemical composition of EP, and the residual components of Chebulae Fructus within processed Chinese medicine might exhibit pharmacological antagonistic effects, thereby achieving the purpose of processing and reducing toxicity. To investigate this further, a combination of UPLC-QTOF-MS-based metabolomics technology and multivariate statistical analysis was employed to analyze and compare the chemical composition of raw and processed EP. Differential variables contributing to group separation were identified based on specific criteria, including VIP (Variable Importance in Projection) values of ≥ 1 in PLS-DA models, p-values < 0.05, and fold changes (FC) > 1.2 or < 0.8. The resulting differentially expressed features were then identified through database matching, literature review, or manual annotation. In total, 47 components were identified from the PEP samples in both positive and negative ionization modes, primarily belonging to flavonoids, terpenoids, organic acids, glycosides, and fatty acids. Among the raw EP group and PEP S4 group, 10 differential compounds were identified. Notably, one toxic terpene and one phenylpropanoid from EP were downregulated, while two bioactive components from Chebulae Fructus were upregulated in the processed group. The possible conversion reactions of these two processing Q-markers were also elucidated. The characteristic processing with Chebulae Fructus resulted in a change in the composition of this Mongolian medicine EP. Furthermore, this study provides a scientific foundation for optimizing the processing technology of EP and offers insights into the processing of other ethnomedicines with toxic properties.Copyright © 2023 Elsevier B.V. All rights reserved.