Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China.
Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
J Ethnopharmacol. 2019 Jan 30;229:222-232. doi: 10.1016/j.jep.2018.10.014. Epub 2018 Oct 17.
As recorded in traditional Chinese medicine (TCM) theory, Genkwa Flos (YH) and Glycyrrhizae Radix et Rhizoma (GC) compose one herbal pair of the so-called "eighteen incompatible medicaments", which indicate pairs of herbs that are mutually incompatible and that theoretically should not be applied simultaneously. However, the theory has been called into question due to a lack of evidence.
In this study, the incompatibility of YH and GC was investigated based on an assessment of the toxic effects of their combination by traditional safety methods and a modern metabonomic approach.
Sprague-Dawley rats were used to evaluate the subacute toxicity of YH and YH-GC. The serum, urine, and several tissues were collected for biochemical analysis, histopathological examination, and metabonomic analysis.
Rats exposed to a dose of 1.0 g/kg YH (3 times of the Chinese Pharmacopoeia maximum dose) exhibited toxicity of the heart, liver, kidney and testes, and rats exposed to a YH-GC combination (1.0 g/kg YH + 1.0 g/kg GC) exhibited similar hepatotoxicity, which aggravated renal and reproductive toxicity. Following this, a metabonomic study tentatively identified 14 potential biomarkers in the YH group and 10 potential biomarkers in the YH-GC group, and metabolic pathways were then constructed. YH disturbed the pathways of glycerophospholipid metabolism, primary bile acid biosynthesis, and sphingolipid metabolism, while YH-GC combination induced disruptions in phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and glycerophospholipid metabolism.
The toxicities of YH and YH-GC combination above the Chinese Pharmacopoeia dose were obvious but different. Metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of the YH-GC combination that caused liver, kidney and reproductive injuries in rats.
在传统中医（TCM）理论中记录，款冬花（YH）和甘草（GC）组成了所谓的“十八反药”中的一对草药，这表明这对草药是相互不相容的，理论上不应同时使用。然而，由于缺乏证据，该理论受到了质疑。
在这项研究中，通过传统安全方法和现代代谢组学方法评估它们组合的毒性作用，研究了 YH 和 GC 的不相容性。
使用 Sprague-Dawley 大鼠评估 YH 和 YH-GC 的亚急性毒性。收集血清、尿液和几种组织进行生化分析、组织病理学检查和代谢组学分析。
暴露于 1.0 g/kg YH（中国药典最大剂量的 3 倍）的大鼠表现出心脏、肝脏、肾脏和睾丸毒性，而暴露于 YH-GC 组合（1.0 g/kg YH + 1.0 g/kg GC）的大鼠表现出类似的肝毒性，加重了肾脏和生殖毒性。随后，代谢组学研究初步鉴定了 YH 组中的 14 个潜在生物标志物和 YH-GC 组中的 10 个潜在生物标志物，并构建了代谢途径。YH 干扰了甘油磷脂代谢、初级胆汁酸生物合成和鞘脂代谢途径，而 YH-GC 组合则诱导了苯丙氨酸、酪氨酸和色氨酸生物合成、酪氨酸代谢和甘油磷脂代谢的破坏。
YH 和 YH-GC 组合在超过中国药典剂量时的毒性明显但不同。代谢组学结合生化和组织病理学方法可用于阐明导致大鼠肝、肾和生殖损伤的 YH-GC 组合的毒性机制。
