Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance.
Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance.
复制标题
DOI：
10.1186/s12967-016-0921-x
复制
发表时间：
2016-06-08
影响因子：
7.4
通讯作者：
Lin N
中科院分区：
文献类型：
--
作者：
Guo Q;Mao X;Zhang Y;Meng S;Xi Y;Ding Y;Zhang X;Dai Y;Liu X;Wang C;Li Y;Lin N
桂枝逍遥知母汤被广泛用于类风湿性关节炎的治疗。经多项长期临床试验证明，桂枝汤治疗类风湿性关节炎疗效显著，且无明显副作用。然而，由于缺乏适当的科学方法，其药理机制尚不清楚。采用药物靶点预测、网络分析和实验验证相结合的综合方法研究GSZD的作用机制。共确定了GSZD的165种评估化学成分的77个假定目标。在计算了所创建的药物靶点网络中节点和边缘的拓扑特征后，我们确定了一个候选的GSZD靶向信号轴，该信号轴包含两个可能的GSZD靶点[组蛋白脱乙酰酶1和热休克蛋白90 kDaα，A类成员1(HSP90AA1)]和三个已知的RA相关靶点[NFKB2；B细胞中kappa轻多肽基因增强子的抑制因子，激酶β(IKBKB)；和肿瘤坏死因子-α(TNF-α)]。这个信号轴可以连接不同的功能模块，这些功能模块与各种与RA相关的信号通路密切相关，包括T/B细胞受体、Toll样受体、核因子-kappaB和肿瘤坏死因子途径，以及破骨细胞分化。此外，还通过体内外实验验证了桂枝汤对RA的治疗作用及其可能的分子机制。桂枝汤可能通过逆转炎症免疫系统失衡，调节HDAC1-HSP90AA1-NFKB2-IKBKB-肿瘤坏死因子-α信号轴而部分减轻RA。本文的在线版本(doi：10.1186/s12967-0160921-x)包含补充材料，授权用户可以使用。
Guizhi-Shaoyao-Zhimu decoction (GSZD) has been extensively used for rheumatoid arthritis (RA) therapy. Marked therapeutic efficacy of GSZD acting on RA has been demonstrated in several long-term clinical trials without any significant side effects. However, its pharmacological mechanisms remain unclear due to a lack of appropriate scientific methodology. GSZD’s mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation. A total of 77 putative targets were identified for 165 assessed chemical components of GSZD. After calculating the topological features of the nodes and edges in the created drug-target network, we identified a candidate GSZD-targeted signal axis that contained interactions between two putative GSZD targets [histone deacetylase 1 (HDAC1) and heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1)] and three known RA-related targets [NFKB2; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKBKB); and tumor necrosis factor-alpha (TNF-α)]. This signal axis could connect different functional modules that are significantly associated with various RA-related signaling pathways, including T/B cell receptor, Toll-like receptor, NF-kappa B and TNF pathways, as well as osteoclast differentiation. Furthermore, the therapeutic effects and putative molecular mechanisms of GSZD’s actions on RA were experimentally validated in vitro and in vivo. GSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1–HSP90AA1–NFKB2–IKBKB–TNF-α signaling axis. The online version of this article (doi:10.1186/s12967-016-0921-x) contains supplementary material, which is available to authorized users.