| Title | Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance |
| Authors | Guo, Qiuyan Mao, Xia Zhang, Yanqiong Meng, Shuqin Xi, Yue Ding, Yi Zhang, Xiaocun Dai, Yuntao Liu, Xia Wang, Chao Li, Yuting Lin, Na |
| Affiliation | China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China. Peking Univ, Beijing Jishuitan Hosp, Dept Pathol, Beijing 100035, Peoples R China. Wuhan Univ Technol, Sch Chem Chem Engn & Life Sci, Wuhan 430070, Hubei, Peoples R China. |
| Keywords | TCM herbal formula Rheumatoid arthritis Guizhi-Shaoyao-Zhimu decoction Network pharmacology Experimental validation TRADITIONAL CHINESE MEDICINE NF-KAPPA-B INTERACTION DATABASE NETWORK PHARMACOLOGY KNOWLEDGEBASE TARGET PERSPECTIVE MECHANISMS RESPONSES PATHWAYS |
| Issue Date | 2016 |
| Publisher | JOURNAL OF TRANSLATIONAL MEDICINE |
| Citation | JOURNAL OF TRANSLATIONAL MEDICINE.2016,14. |
| 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-alpha)]. 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-alpha signaling axis. |
| URI | http://hdl.handle.net/20.500.11897/433415 |
| ISSN | 1479-5876 |
| DOI | 10.1186/s12967-016-0921-x |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 北京积水潭医院 |
