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- Title
Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance.
- Authors
Qiuyan Guo; Xia Mao; Yanqiong Zhang; Shuqin Meng; Yue Xi; Yi Ding; Xiaocun Zhang; Yuntao Dai; Xia Liu; Chao Wang; Yuting Li; Na Lin; Guo, Qiuyan; Mao, Xia; Zhang, Yanqiong; Meng, Shuqin; Xi, Yue; Ding, Yi; Zhang, Xiaocun; Dai, Yuntao
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>GSZD's mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation.<bold>Results: </bold>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.<bold>Conclusions: </bold>GSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1-HSP90AA1-NFKB2-IKBKB-TNF-α signaling axis.
- Subjects
CHINESE medicine; RHEUMATOID arthritis treatment; TARGETED drug delivery; TUMOR necrosis factors; BIOCHEMICAL mechanism of action; INFLAMMATION treatment; TOLL-like receptors; DRUG therapy for arthritis; ANIMALS; ARTHRITIS; CELLULAR signal transduction; COMBINATION drug therapy; HERBAL medicine; IMMUNE system; INFLAMMATION; JOINTS (Anatomy); RATS; RHEUMATOID arthritis; SYNOVITIS; SEVERITY of illness index; DISEASE progression; DISEASE complications
- Publication
Journal of Translational Medicine, 2016, Vol 14, p1
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-016-0921-x