Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalan
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Guo et al. J Transl Med (2016) 14:165 DOI 10.1186/s12967-016-0921-x
Open Access
RESEARCH
Guizhi‑Shaoyao‑Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation‑immune system imbalance Qiuyan Guo1†, Xia Mao1†, Yanqiong Zhang1*†, Shuqin Meng2, Yue Xi2, Yi Ding2, Xiaocun Zhang3, Yuntao Dai1, Xia Liu3, Chao Wang1, Yuting Li1 and Na Lin1*
Abstract Background: 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. Methods: GSZD’s mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation. Results: 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 factoralpha (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. Conclusions: GSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1–HSP90AA1–NFKB2–IKBKB–TNF-α signaling axis. Keywords: TCM herbal formula, Rheumatoid arthritis, Guizhi-Shaoyao-Zhimu decoction, Network pharmacology, Experimental validation Background Rheumatoid arthritis (RA) is a chronic, debilitating inflammatory joint disease characterized by synovial inflammation and the progressive destruction of cartilage *Correspondence: [email protected]; [email protected] † Qiuyan Guo, Xia Mao and Yanqiong Zhang equally contributed to this work 1 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China Full list of author information is available at the end of the article
and bone [1]. Several studies have indicated that RA has a prevalence rate of approximately 0.5 to 1 % in adult populations in developed countries [2]. Moreover, growing evidence indicates that RA patients are more at risk of developing a collection of comorbidities that have no typical features and are difficult to diagnose, leading them to have poorer clinical outcomes than that of the
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