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 Beijing 102488, China.
Zhongguo Zhong Yao Za Zhi. 2020 Jul;45(14):3275-3281. doi: 10.19540/j.cnki.cjcmm.20200210.403.
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.
金银花具有悠久的清热泻火解毒功效历史。历代《中国药典》对其功效的描述相对稳定，是研究功效标志物的优良载体。本研究以系统中医理论为指导，以金银花清热泻火解毒功效体系为例，阐明金银花在清热泻火解毒功效体系中的要素（活性成分），确定边界（信号通路），建立结构（系统动力学模型），识别与药理、功效和作用（清热泻火解毒作用）相对应的系统功能，探索系统动力学模型在中药功效标志物发现中的应用。本文建立了体内白细胞介素1（IL-1）和白细胞介素6（IL-6）的动态模型，通过动态网络预测金银花不同成分及其组合在IL-1和IL-6信号通路中相关因子的表达，从而寻找金银花清热泻火解毒的有效标志物。结果表明，绿原酸浓度越低，绿原酸与芳樟醇组合对IL-1下游Jun氨基末端激酶（JNK）的抑制率越高；IL-6通路中木犀草素浓度越高，绿原酸与木犀草素组合对IL-6下游C反应蛋白（CRP）的抑制率越高。揭示了基于IL-1信号通路的金银花清热泻火解毒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泻火解毒潜在功效标志物为绿原酸和木犀草素。本研究为中药功效标志物的发现提供了方法学指导。
