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.
Highlights
Uncovering pharmacological mechanisms of Wu-tou decoction acting on rheumatoid arthritis through systems approaches: drug-target prediction, network analysis and experimental validation
With regard to Wu-tou decoction (WTD), Radix Aconiti is the primary component and is believed to be effective in treating rheumatic arthritis and rheumatoid arthritis (RA); Herba Ephedrae serves as the ministerial component to intensify the analgesic function of Radix Aconiti; Radix Astragali acts as the adjunctive component to invigorate qi, strengthen the body and reinforce the effect of Radix Aconiti and Herba Ephedrae; Raidix Paeoniae Alba and Radix Glycytthizae are both messenger drugs which can either focus the actions of the formula on a certain area of the body or harmonize and integrate the actions of the other herbs of the formula[6,7]
Our previous study of network analysis showed that the predicted effectors of WTD might be involved in neuroactive ligand-receptor interaction and calcium signaling pathway[10], the pharmacological mechanisms of WTD acting on RA have not been fully elucidated
Summary
Uncovering pharmacological mechanisms of Wu-tou decoction acting on rheumatoid arthritis through systems approaches: drug-target prediction, network analysis and experimental validation. Network pharmacology, combined with pharmacology and pharmacodynamics, is a novel research field which is implicated in the application of omics and systems biology-based technologies[11] It clarifies the synergistic effects and the underlying mechanisms of multi-component and multi-target agents by analyzing various networks of the complex and multi-levels interactions[12,13].
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