中国中药杂志

2020, v.45(14) 3275-3281

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基于系统中药学的金银花清热解毒功效标志物研究
Study on efficacy markers of heat-clearing and detoxifying effect of Lonicerae Japonicae Flos based on systematic traditional Chinese medicine

彭莎;霍晓乾;霍梦琪;刘亚楠;张燕玲;乔延江;
PENG Sha;HUO Xiao-qian;HUO Meng-qi;LIU Ya-nan;ZHANG Yan-ling;QIAO Yan-jiang;State Administration of Traditional Chinese Medicine, Research Center of Traditional Chinese Medicine-Information Engineering,Key Technology of Traditional Chinese Medicine Pharmacy and New Drug Development Engineering Research Center of Ministry of Education, School of Chinese Materia Medica, Beijing University of Chinese Medicine;

摘要(Abstract):

金银花的清热解毒功效历史悠久,历版《中国药典》对其功效的描述较为稳定,是研究功效标志物的优良载体。该文以系统中药学理论为指导,以金银花清热解毒功效系统为研究示例,明确了金银花清热解毒功效系统的元素(活性成分),划定了边界(信号通路),建立了结构(系统动力学模型),辨识了其药理、药效和功效相应的系统功能(清热解毒功效),探讨系统动力学模型在发现中药功效标志物中的应用。通过建立生物体内白细胞介素-1(interleukin 1,IL-1)、白细胞介素-6(interleukin 6,IL-6)相关动力学模型,通过动态网络预测金银花中不同成分及成分组合在IL-1,IL-6信号通路中相关因子的表达,以期发现金银花清热解毒功效标志物。研究结果表明在IL-1通路中,绿原酸较低浓度下,与芳樟醇组合对IL-1下游Jun氨基末端激酶(Jun N-terminal kinase,JNK)抑制率更高;在IL-6通路中,绿原酸浓度越大,与木犀草素组合对IL-6下游C反应蛋白(C-reactive protein,CRP)抑制率更高;提示基于IL-1信号通路的金银花清热解毒功效的潜在功效标志物为绿原酸和芳樟醇,基于IL-6信号通路的金银花清热解毒功效的潜在功效标志物为绿原酸和木犀草素。该研究为中药功效标志物的发现提供了方法学指导。
Lonicerae Japonicae Flos has a long history of heat-clearing and detoxifying effect. The description of its efficacy in Chinese Pharmacopoeia of past dynasties is relatively stable, and it is an excellent carrier for the study of efficacy markers. Guided by the theory of systematic traditional Chinese medicine, heat-clearing and detoxifying effect efficacy system of Lonicerae Japonicae Flos was taken as an example in this study to clarify the elements(active ingredients) of Lonicerae Japonicae Flos in heat-clearing and detoxifying efficacy system, determine the boundary(signal pathway), establish the structure(system dynamics model), identify the system functions corresponding to pharmacology, efficacy and effects(heat-clearing and detoxifying effect), and explore the application of system dynamics model in the discovery of efficacy markers of traditional Chinese medicine. In this paper, the dynamic models of interleukin 1(IL-1) and interleukin 6(IL-6) in vivo were established to predict the expression of related factors in IL-1 and IL-6 signaling pathways of different components and their combinations in Lonicerae Japonicae Flos by dynamic network, so as to find the effective markers of heat-clearing and detoxification of Lonicerae Japonicae Flos. The results showed that the lower the concentration of chlorogenic acid, the higher the inhibition rate of Jun N-terminal kinase(JNK) at downstream of IL-1 by the combination of chlorogenic acid and linalool; the higher the concentration of luteolin in IL-6 pathway, the higher the inhibition rate of C-reactive protein(CRP) at downstream of IL-6 by the combination of chlorogenic acid and luteolin. It revealed that the potential efficacy markers of Lonicerae Japonicae Flos in heat-clearing and detoxifying effect based on IL-1 signaling pathway were chlorogenic acid and linalool, and the potential efficacy markers of Lonicerae Japonicae Flos in heat-clearing and detoxifying effect based on IL-6 signaling pathway were chlorogenic acid and luteolin. This study provided methodological guidance for the discovery of efficacy markers of traditional Chinese medicine.

关键词(KeyWords): 系统中药学;金银花;清热解毒;IL-1;IL-6;功效标志物
systematic traditional Chinese medicine;Lonicerae Japonicae Flos;heat-clearing and detoxifying effect;IL-1;IL-6;efficacy makers

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基金项目(Foundation): 国家自然科学基金项目(81573831,81430094)

作者(Author): 彭莎;霍晓乾;霍梦琪;刘亚楠;张燕玲;乔延江;
PENG Sha;HUO Xiao-qian;HUO Meng-qi;LIU Ya-nan;ZHANG Yan-ling;QIAO Yan-jiang;State Administration of Traditional Chinese Medicine, Research Center of Traditional Chinese Medicine-Information Engineering,Key Technology of Traditional Chinese Medicine Pharmacy and New Drug Development Engineering Research Center of Ministry of Education, School of Chinese Materia Medica, Beijing University of Chinese Medicine;

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