目的 应用代谢组学技术分析生、熟大黄化学成分变化及其入血成分差异，揭示炮制对大黄Rhei Radix et Rhizoma物质基础的影响。方法 采用UPLC-MS/MS法对生、熟大黄的体内外化学成分进行信息采集，结合化合物特征碎片离子与裂解途径进行鉴定，之后运用多元统计分析筛选差异成分。结果 共鉴定生、熟大黄体外成分201个（蒽醌类45个、鞣质类43个、黄酮类52个、二苯乙烯类21个、酚酸类12个、苯丙素类7个、色原酮类3个、芳香醛类2个及其他类16个），筛选出23个生、熟大黄中存在显著差异的成分，其中与生大黄相比，大黄酚、没食子酸、儿茶素等7种成分含量在熟大黄中显著升高（P＜0.05），芦荟大黄素-1-O-β-D-葡萄糖、番泻苷A、原花青素等16种成分含量显著降低（P＜0.05）。血清药物化学研究共鉴定出94个移行成分，包括36个原型成分和58个代谢产物，生、熟大黄体内筛选出11个差异性成分，相较生大黄，熟大黄部分原型与代谢产物血药浓度升高，特别是鞣质单体如没食子酸等原型成分，以及部分蒽醌类Ⅱ代谢产物相对含量显著升高。结论 生、熟大黄体内外代谢轮廓发生显著改变，差异性成分主要体现在蒽醌类、鞣质类等，与生大黄相比，熟大黄中多数结合型蒽醌向游离型蒽醌转化，可水解类鞣质聚合体分解生成鞣质单体，缩合类鞣质成分与黄酮类苷元成分存在动态转化。化学成分之间的转化，为阐明大黄“生熟异治”的物质基础提供了科学依据。

Objective Utilize metabolomics techniques to analyze the changes in chemical components of raw and steamed Rhei Radix et Rhizoma and the differences in their blood-entering components, and to reveal the impact of processing on the material basis of Rhei Radix et Rhizoma. Methods UPLC-MS/MS technology was used to collect the chemical composition information of raw and steamed Rhei Radix et Rhizoma in vitro and in vivo. Identification was carried out by combining the characteristic fragment ions and fragmentation pathways of the compounds. Multivariate statistical analysis was combined to screen for differential markers. Results A total of 201 components were identified in both raw and steamed Rhei Radix et Rhizoma, including 45 anthraquinones, 43 tannins, 52 flavonoids, and 21 stilbenes, 12 phenolic acids, seven phenylpropanoids, three chromones, two aromatic aldehydes, and 16 other compounds. After steaming, 23 common components showed significant changes. Among them, seven components such as aloeemodin, gallic acid, and catechin were significantly upregulated (P < 0.05), and 16 components such as aloeemodin-1-O-β-D-glucopyranoside, sennoside A, and proanthocyanidins were significantly downregulated (P < 0.05). A total of 36 prototype components and 58 metabolites were identified in the drug-containing serum. 11 common components showed significant changes in raw and steamed Rhei Radix et Rhizoma compared with raw Rhei Radix et Rhizoma, the blood drug concentrations of some prototype and metabolite components in steamed Rhei Radix et Rhizoma increased. In particular, the blood concentration of the tannin monomer gallic acid, which is a prototype component entering the blood, and the blood concentration of prototype aglycone-type components increased. The relative content of some phase-Ⅱ metabolites of anthraquinones significantly increased. Conclusion The in-vitro and in-vivo metabolic profiles of raw and steamed Rhei Radix et Rhizoma have changed significantly. The differential components are mainly in anthraquinones, tannins, etc. Compared with raw Rhei Radix et Rhizoma, in steamed Rhei Radix et Rhizoma, most conjugated anthraquinones were converted into free anthraquinones, hydrolysable tannin polymers were decomposed into tannin monomers, and there was a dynamic transformation between condensed tannin components and flavonoid aglycone components. These conversions of components can provide a scientific basis for clarifying the material basis of the “different treatments for raw and steamed Rhei Radix et Rhizoma ”.

R284.1

河南省中医药科研专项课题（2024ZY1033）