Wu Qi, Hou Zong, Liu Zhiqiang, Zheng Zhong, Xing Junpeng, Sun Rong, Liu Shu
State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun, Jilin Provincial Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230029, China.
State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun, Jilin Provincial Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
J Ethnopharmacol. 2025 Jul 24;351:120106. doi: 10.1016/j.jep.2025.120106. Epub 2025 Jun 6.
Polygoni Multiflori Radix (PMR) and Rhei Radix et Rhizoma (RRR), two commonly used traditional Chinese medicine (TCM) for the treatment of constipation, have raised safety concerns due to increasing reports of hepatorenal toxicity in recent years. Despite their therapeutic applications, the specific toxic components, dose-dependent effects, and molecular mechanisms underlying their toxicity remain poorly characterized.
Given that PMR and RRR belong to the Polygonaceae family and share structural similarities in their chemical constituents, this study aimed to systematically compare their chemical profiles and toxicity patterns. By elucidating the correlation between compositional variations and hepatotoxic outcomes, we sought to identify the key toxic components and potential mechanisms driving their adverse effects.
The toxicological effects of PMR and RRR were examined by in vivo and in vitro toxicity assessments. Subsequently, the in vitro and in vivo components of PMR and RRR were analyzed by UHPLC-MS, and the similarities and differences between them were assessed to anticipate potential toxic components. Finally, the toxicity of the representative components was evaluated by in vitro cytotoxicity tests to validate the findings of the component analysis.
Both in vitro and in vivo studies demonstrated that RRR exhibited greater toxicity than PMR, though their toxic manifestations. The results of composition analysis showed that anthraquinones were the main active components of PMR and RRR. In vitro toxicity assessments of representative components revealed that free anthraquinones showed higher toxicity than anthraquinone glycosides; naphthalenes exhibited significant toxicity, while tannins were non-toxic at the tested concentrations. When used alone, stilbenes have low toxicity. Nevertheless, they may have a synergistic harmful effect with anthraquinones.
Free anthraquinones and naphthalenes were identified as the primary hepatotoxic components in PMR and RRR. RRR is riskier than PMR because of its higher concentration of free anthraquinones. These findings provide a critical reference for future mechanistic studies and safety evaluations of Polygonaceae-derived TCM, highlighting the need for stringent quality control measures to mitigate toxicity risks.
何首乌（PMR）和大黄（RRR）是两种常用于治疗便秘的传统中药，近年来，由于肝肾毒性报告的增加，它们引发了安全担忧。尽管它们有治疗应用，但具体的有毒成分、剂量依赖性效应及其毒性的分子机制仍不清楚。
鉴于何首乌和大黄属于蓼科，其化学成分在结构上有相似之处，本研究旨在系统比较它们的化学特征和毒性模式。通过阐明成分变化与肝毒性结果之间的相关性，我们试图确定关键的有毒成分及其产生不良反应的潜在机制。
通过体内和体外毒性评估来研究何首乌和大黄的毒理学效应。随后，采用超高效液相色谱-质谱联用（UHPLC-MS）分析何首乌和大黄的体内外成分，并评估它们之间的异同，以预测潜在的有毒成分。最后，通过体外细胞毒性试验评估代表性成分的毒性，以验证成分分析的结果。
体内和体外研究均表明，大黄的毒性比何首乌大，尽管它们的毒性表现有所不同。成分分析结果表明，蒽醌类是何首乌和大黄的主要活性成分。代表性成分的体外毒性评估显示，游离蒽醌的毒性高于蒽醌苷；萘类表现出显著毒性，而单宁在测试浓度下无毒。单独使用时，芪类毒性较低。然而，它们可能与蒽醌类产生协同有害作用。
游离蒽醌和萘类被确定为何首乌和大黄中的主要肝毒性成分。大黄比何首乌风险更高，因为其游离蒽醌浓度更高。这些发现为未来蓼科衍生中药的作用机制研究和安全性评估提供了重要参考，强调了采取严格质量控制措施以降低毒性风险的必要性。
