title: Uncovering pharmacological mechanisms of Wu-tou decoction acting on rheumatoid arthritis through systems approaches: drug-target prediction, network analysis and experimental validation.
abstract: Wu-tou decoction (WTD) has been extensively used for the treatment of rheumatoid arthritis (RA). Due to lack of appropriate methods, pharmacological mechanisms of WTD acting on RA have not been fully elucidated. In this study, a list of putative targets for compositive compounds containing in WTD were predicted by drugCIPHER-CS. Then, the interaction network of the putative targets of WTD and known RA-related targets was constructed and hub nodes were identified. After constructing the interaction network of hubs, four topological features of each hub, including degree, node betweenness, closeness and k-coreness, were calculated and 79 major hubs were identified as candidate targets of WTD, which were implicated into the imbalance of the nervous, endocrine and immune (NEI) systems, leading to the main pathological changes during the RA progression. Further experimental validation also demonstrated the preventive effects of WTD on inflammation and joint destruction in collagen-induced arthritis (CIA) rats and its regulatory effects on candidate targets both in vitro and in vivo systems. In conclusion, we performed an integrative analysis to offer the convincing evidence that WTD may attenuate RA partially by restoring the balance of NEI system and subsequently reversing the pathological events during RA progression.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Bai
authors.affiliation: Tianjin International Joint Academy of Biotechnology &Medicine, Tianjin 300457, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Danhua
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Yini
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.affiliation: 1] Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China [2] MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Shao
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004703:Endocrine System / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology
chemical_list: D004365:Drugs, Chinese Herbal
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