Journal of ethnopharmacology · 2025
The difference of composition between polygoni Multiflori Radix and Rhei Radix et Rhizoma revealed their primary hepatotoxicity components.
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Wu Qi, Hou Zong, Liu Zhiqiang, Zheng Zhong, Xing Junpeng, Sun Rong, Liu Shu
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: 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.
AIM OF THE STUDY: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
AIM OF THE STUDY: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.