Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalanceReport as inadecuate

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Journal of Translational Medicine

, 14:165

Medical bioinformatics


BackgroundGuizhi-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.

MethodsGSZD’s mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation.

ResultsA 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.

ConclusionsGSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1–HSP90AA1–NFKB2–IKBKB–TNF-α signaling axis.

KeywordsTCM herbal formula Rheumatoid arthritis Guizhi-Shaoyao-Zhimu decoction Network pharmacology Experimental validation Qiuyan Guo, Xia Mao and Yanqiong Zhang equally contributed to this work

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-016-0921-x contains supplementary material, which is available to authorized users.

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Author: Qiuyan Guo - Xia Mao - Yanqiong Zhang - Shuqin Meng - Yue Xi - Yi Ding - Xiaocun Zhang - Yuntao Dai - Xia Liu - Chao Wan


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