Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
J Ethnopharmacol. 2021 Oct 28;279:113822. doi: 10.1016/j.jep.2021.113822. Epub 2021 Jan 16.
Precise target distribution is a key issue for further appropriate applications of fangjis (formulas) with similar efficacy and herbal constituents to maximize efficacy and minimize toxicity.
To develop an algorithm for investigating the differential target distributions and characteristic mechanisms of fangjis.
In this study, we proposed a Modulome-Fangjiome Association Study (MoFAS) for comparing fangjis from qi-invigorating and xue-nourishing fangjiome (represented by four fangjis: FEJ, SDT, LYG and QOL). Firstly, the database-driven target network of these 4 fangjis was constructed as qi-xue network and decomposed into modules. Then, the modular map with functional landscape were constructed based on consistency score and enrichment analysis. Finally, we employed a targeting rate (TR) matrix to assess the contribution of this fangjiome to modulome (a set of modules) and compared characteristic effect of fangjis by principal component analysis (PCA).
A qi-xue network constituted by 579 proteins and 23 modules were constructed. In the functional landscape, 3 primary modules were mainly involved in the endocrine system and environmental adaptation. For the target distribution, SDT and QOL were more similar; the FEJ and LYG were located distant from other fangjis according to PCA. The common effects of FEJ, SDT, and QOL focused on stress response and organism development in environmental perturbation, but the FEJ was superior in regulating critical targets, primarily focusing on hormone and neurotransmitter processes. SDT and QOL were concentrated on the majority scale of the qi-xue network, especially for the mitotic cell cycle and development. LYG only targeted lymphocyte costimulation and icosanoid biosynthetic processes.
In this study, for the first time, we investigated the difference in the target distribution of qi-invigorating and xue-nourishing fangjiome and provided direct evidence for the characteristic therapeutic effect of these fangjis, which may promote the precise application of fangjis and support the identification of appropriate populations.
精确定位靶标是将具有相似功效和草药成分的方剂进一步适当应用的关键问题，以最大限度地提高功效和降低毒性。
开发一种用于研究方剂差异靶标分布和特征机制的算法。
在这项研究中，我们提出了一种比较补气养血方剂（以四剂：FEJ、SDT、LYG 和 QOL 为代表）的调制体-方剂关联研究（MoFAS）。首先，构建了 4 个方剂的基于数据库的靶标网络，作为气-血网络，并将其分解为模块。然后，基于一致性评分和富集分析构建了具有功能景观的模块化图谱。最后，我们采用靶向率（TR）矩阵来评估该方剂家族对调制体（一组模块）的贡献，并通过主成分分析（PCA）比较方剂的特征效应。
构建了一个由 579 个蛋白质和 23 个模块组成的气-血网络。在功能景观中，主要涉及内分泌系统和环境适应的 3 个主要模块。对于靶标分布，SDT 和 QOL 更为相似；FEJ 和 LYG 根据 PCA 与其他方剂的距离较远。FEJ、SDT 和 QOL 的共同作用主要集中在环境干扰下的应激反应和生物体发育方面，但 FEJ 在调节关键靶标方面更为优越，主要集中在激素和神经递质过程。SDT 和 QOL 集中在气-血网络的大部分区域，特别是有丝分裂细胞周期和发育。LYG 仅靶向淋巴细胞共刺激和icosanoid 生物合成过程。
在这项研究中，我们首次研究了补气养血方剂的靶标分布差异，并为这些方剂的特征治疗效果提供了直接证据，这可能促进方剂的精确应用，并支持合适人群的识别。
