Huang Lin, Lv Qi, Xie Duoli, Shi Tieliu, Wen Chengping
TCM Clinical Basis Institute, Zhejiang Chinese Medicine University, 548 Binwen Road, Hangzhou, Zhejiang, 310000, China.
Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, School of Life Science, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.
Sci Rep. 2016 Mar 3;6:22602. doi: 10.1038/srep22602.
Gui-Zhi-Shao-Yao-Zhi-Mu (GSZ) decoction is a Traditional Chinese Medicine (TCM) formula commonly used for the treatment of Rheumatoid Arthritis (RA). The therapeutic effect of GSZ for RA treatment is supported by our clinical retrospective study. To uncover the potential mechanism underlying GSZ formula, we identified 1,327 targets of 673 compounds from 9 herbs that involve in Fc epsilon RI signaling pathway and regulation of immunoglobulin production. Comparison between formula targets with 79 RA drug targets and 675 RA disease genes showed that formula targets covered 31.6% RA drug targets and 19.9% RA disease genes. Formula specific targets presented expression patterns highly similar to the disease genes and drug targets based on the expression profiles of RA samples. Investigation of 10 inferred gene clusters from expression profiles with a target association network revealed that formula specific targets directly or indirectly interacted with disease genes that were essential for immune related biological processes (e.g. inflammatory responses, treatment response of rheumatoid arthritis, etc.). Our result indicated that GSZ disrupted the RA disease dysfunction modules and restored homeostasis in the human body. The systemic approach to infer therapeutic mechanisms of GSZ for RA treatment provides a new insight in the understanding of this TCM formula.
桂枝芍药知母汤（GSZ）是一种常用于治疗类风湿性关节炎（RA）的中药方剂。我们的临床回顾性研究支持了GSZ治疗RA的疗效。为了揭示GSZ方剂潜在的作用机制，我们从9味中药中鉴定出673种化合物的1327个靶点，这些靶点涉及FcεRI信号通路和免疫球蛋白产生的调节。将方剂靶点与79个RA药物靶点和675个RA疾病基因进行比较，结果显示方剂靶点覆盖了31.6%的RA药物靶点和19.9%的RA疾病基因。基于RA样本的表达谱，方剂特异性靶点呈现出与疾病基因和药物靶点高度相似的表达模式。通过将表达谱与靶点关联网络中推断出的10个基因簇进行研究，发现方剂特异性靶点直接或间接与对免疫相关生物学过程（如炎症反应、类风湿性关节炎的治疗反应等）至关重要的疾病基因相互作用。我们的结果表明，GSZ破坏了RA疾病功能失调模块并恢复了人体的内环境稳态。推断GSZ治疗RA机制的系统方法为理解这一中药方剂提供了新的视角。
