基于成分在病态下向血液迁移及其体内过程，明确乌头汤药效成分和作用机制的综合策略。
A comprehensive strategy to clarify the pharmacodynamic constituents and mechanism of Wu-tou decoction based on the constituents migrating to blood and their in vivo process under pathological state.
机构信息
State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Provincial Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, 230026, Hefei, China.
Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, 130021, Changchun, China.
出版信息
J Ethnopharmacol. 2021 Jul 15;275:114172. doi: 10.1016/j.jep.2021.114172. Epub 2021 Apr 28.
ETHNOPHARMACOLOGICAL RELEVANCE
As a traditional Chinese medicine (TCM) formula, Wu-tou decoction has been used for treating rheumatoid arthritis (RA) for more than a thousand years. Identifying pharmacodynamic constituents (PCs) of WTD and exploring their in vivo process are very meaningful for promoting the modernization of TCM. However, the pathological state might change this process.
AIM OF THE STUDY
Hence, it is necessary and significant to compare the process in vivo of drugs both in normal and disease state and clarify their action mechanism.
MATERIALS AND METHODS
Taking Wu-tou decoction (WTD) as the research object, a comprehensive strategy based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to identify PCs, clarify and compare their absorption and distribution in normal and model rats, and then explore the potential mechanism of TCM. Firstly, the PCs in WTD were identified. Then, the pharmacokinetics (PK) and tissue distribution of these ingredients were studied. Finally, the constituents with the difference between normal and model rats were selected for target network pharmacological analysis to clarify the mechanism.
RESULTS
A total of 27 PCs of WTD were identified. The absorption and distribution of 20 PCs were successfully analyzed. In the disease state, the absorption and distribution of all these components were improved to have better treatment effects. The results of target network pharmacological analysis indicated that PTGS1, PTGS2, ABCB1, SLC6A4, CHRM2, ESR1, ESR2, CDK2, TNF and IL-6 are 10 key targets for WTD against RA. The regulatory effects of WTD on the expression of PTGS2 and TNF were further verified. Pathway enrichment analysis showed that the key mechanism of WTD against RA is to reduce inflammation and regulate the immune response.
CONCLUSION
These results indicated that this strategy could better understand the in vivo process and mechanism of WTD under the pathological state. Furthermore, this strategy is also appropriate for other TCM.
民族药理学相关性
作为一种传统的中药（TCM）配方，乌头汤已被用于治疗类风湿关节炎（RA）超过一千多年。鉴定 WTD 的药效成分（PCs）并探索其体内过程对于促进 TCM 的现代化非常有意义。然而，病理状态可能会改变这个过程。
研究目的
因此，有必要比较正常和疾病状态下药物的体内过程，并阐明其作用机制。
材料和方法
以乌头汤（WTD）为研究对象，建立了一种基于液相色谱-质谱联用（LC-MS）的综合策略，以鉴定 PCs，阐明并比较其在正常和模型大鼠中的吸收和分布情况，然后探讨 TCM 的潜在机制。首先，鉴定 WTD 中的 PCs。然后，研究这些成分的药代动力学（PK）和组织分布。最后，选择正常和模型大鼠之间存在差异的成分进行目标网络药理学分析，以阐明其机制。
结果
共鉴定出 27 种 WTD 的 PCs。成功分析了 20 种成分的吸收和分布。在疾病状态下，所有这些成分的吸收和分布都得到了改善，从而具有更好的治疗效果。目标网络药理学分析结果表明，PTGS1、PTGS2、ABCB1、SLC6A4、CHRM2、ESR1、ESR2、CDK2、TNF 和 IL-6 是 WTD 治疗 RA 的 10 个关键靶点。进一步验证了 WTD 对 PTGS2 和 TNF 表达的调节作用。通路富集分析表明，WTD 治疗 RA 的关键机制是减轻炎症和调节免疫反应。
结论
这些结果表明，该策略可以更好地了解病理状态下 WTD 的体内过程和机制。此外，该策略也适用于其他 TCM。
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