目的 根据历代本草记载的辅料种类，对比不同辅料炮制何首乌的减毒效果差异，为优选何首乌炮制减毒的辅料提供参考。方法 采用UPLC-Q/TOF-MS表征不同辅料炮制何首乌样品的化学信息，以培养的正常人肝L02细胞为对象评价肝细胞毒性，综合比较不同辅料炮制何首乌的减毒效果差异及成分变化规律。结果 不同辅料对何首乌炮制后的化学指纹图谱、指标性成分及肝细胞毒性有不同程度的影响，在相同蒸制压力和时间条件下，黑豆、米泔水或大枣蒸制对何首乌的主要成分包括没食子酸、儿茶素、顺式二苯乙烯苷、反式二苯乙烯苷、大黄素-8-O-β-D-葡萄糖苷、大黄素甲醚和大黄素及肝细胞毒性的影响相对较大，减毒效果最好的3种辅料分别为米泔水 > 大枣 > 黑豆。通过简单相关和多元相关综合分析，提示顺式二苯乙烯苷可能是何首乌肝细胞毒性相关的主要化学成分，大黄素-8-O-β-D-葡萄糖苷可能是何首乌潜在的毒性相关成分。结论 传统记载的不同辅料用于何首乌炮制均可减毒，目前除了常用的黑豆有较好的减毒效果外，米泔水或大枣也可作为何首乌炮制减毒的候选辅料。

Objective To provide references for optimizing adjuvants with Polygoni Multiflori Radix (PMR), we compared the effects of detoxification by different adjuvants processing according to Chinese medicine's records of past dynasties. Methods The chemical information of all samples including crude and processed PMR with different adjuvants was characterized by UPLC-Q-TOF-MS, and the normal human hepatocytes (L02 cell line) was cultured in vitro to evaluate the cytotoxicity, then we gave synthetic analyses on effects of processed PMR with different adjuvants for toxicity-decreasing and variations of chemical contents. The difference of toxicity reducing effect and the rule of composition change of PMR processed with different adjuvants were compared comprehensively. Results Different adjuvants had different level of effects on chemical fingerprint, index component and cytotoxicity of PMR under the same conditions of pressure and time. More specifically, black bean, jujube and rice-rinsing water had greater impact on PMR main components including gallic acid, catechins, cis-stilbene glycoside, trans-stilbene glycoside, emodin-8-O-β-D-glucoside, physcion and emodin as well as hepatotoxicity. The three adjuvants with the best toxicity-decreasing effects were in sequence of rice-rinsing water > jujube > black bean. Furthermore, comprehensive analysis of simple correlation and multiple correlation suggested that cis-stilbene glycoside might be the main chemical component contributed to hepatotoxicity of PMR, and emodin-8-O-β-D-glucoside might be the potential toxicity component. Conclusion Different adjuvants traditionally recorded can attenuate the toxicity of PMR. In addition to black beans, rice-rinsing water and jujube can also be used as candidate adjuvants for the toxicity-decreasing of PMR.

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国家“重大新药创制”科技重大专项课题：基于临床的中药何首乌肝毒性生物标记物研究（2015ZX09501-004-001-008）；国家公益性行业专项课题：基于免疫应激的何首乌肝损害易感人群筛查及风险防控对策研究（201507004-04）；国家自然科学基金重点项目：基于临床病证的传统无毒中药肝毒性客观辨识及机制研究（81630100）