Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance
Authors: Xiaocun Zhang
Shuqin Meng
Xia Mao
Chao Wang
Yuntao Dai
Yue Xi
Yuting Li
Yanqiong Zhang
Na Lin
Yi Ding
Xia Liu
Qiuyan Guo
Journal: Journal of translational medicine (2016)
Discipline: CLINICAL MEDICINE
Keywords: Experimental validation; Guizhi-Shaoyao-Zhimu decoction; Network pharmacology; Rheumatoid arthritis; TCM herbal formula.
Affiliations: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China., Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. ., Department of Pathology, Beijing Jishuitan Hospital, Peking University, Beijing, 100035, China., School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Hubei, 430070, China.

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

Retracted: No

PubPeer comments:
  Fig. 7 Effect of GSZD on histologic lesions of AIA rats. a Inflammatory changes observed in different groups using H E staining (u00d7200); b Articular cartilage changes observed in different groups using H E staining (u00d7200); **c Cartilage changes observed in different groups using toluidine blue staining; (u00d7200)**; d Bone destruction changes observed in different groups using H E staining (u00d7200) ![file] Panels for GSZD 18.6 g kg and MTX 0.2 mg kg in (c) seem to be the same, apart from vertical rescaling and a 2-deg rotation. Could the authors check? ![file] ,