Chen Yan-Yan, Chen Jia-Qian, Tang Yu-Ping, Shang Er-Xin, Zhao Qi, Zou Jun-Bo, Xu Ding-Qiao, Yue Shi-Jun, Yang Jie, Fu Rui-Jia, Zhou Gui-Sheng, Duan Jin-Ao
Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research and Development of Characteristic Qin Medicine Resources (Cultivation), and 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, Shaanxi Province, 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, Jiangsu Province, China.
Chin Med. 2022 Nov 19;17(1):130. doi: 10.1186/s13020-022-00687-4.
Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose-response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment.
The proposed methodology of integrated dose-response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose-response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM.
This developed strategy was successfully applied to rhubarb. The dose-response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case.
An integrated dose-response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics.
中药已被用于治疗各种疾病数千年。然而，剂量的不确定性以及缺乏药理学和毒理学的系统评价是中药仍然神秘且未被全球接受的一个主要原因。因此，我们旨在提出一种基于治疗效果和不良反应的综合剂量反应代谢组学策略，以指导中药治疗中的剂量选择。
所提出的综合剂量反应代谢组学方法包括四个步骤：剂量设计、代谢特征的多重比较、反应计算和剂量反应曲线拟合。通过比较不同剂量下所有代谢物的变化并通过叠加计算这些变化，可以表征整体扰动，从而描述不同剂量中药诱导的整体效应和毒性。选择常用于治疗便秘的大黄作为代表性中药。
该开发的策略成功应用于大黄。剂量反应曲线清楚地显示了大黄在不同剂量下的疗效和不良反应。选择0.69 g/kg的大黄剂量（相当于临床中的7.66 g）作为最佳剂量，因为它是有效剂量的90%，且在这种情况下三种不良反应是可接受的。
首次建立了一种反映治疗效果和不良反应的综合剂量反应代谢组学策略，我们认为这有助于揭开中药剂量的神秘面纱。此外，该策略有利于中药的现代化和国际化，并拓宽了代谢组学的应用。
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