Abstract
Traditional Chinese medicine (TCM) with the characteristics of “multi-component-multi-target-multi-pathway” has obvious advantages in the prevention and treatment of complex diseases, especially in the aspects of “treating the same disease with different treatments”. However, there are still some problems such as unclear substance basis and molecular mechanism of the effectiveness of formula. Network pharmacology is a new strategy based on system biology and poly-pharmacology, which could observe the intervention of drugs on disease networks at systematical and comprehensive level, and especially suitable for study of complex TCM systems. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, causing articular and extra articular dysfunctions among patients, it could lead to irreversible joint damage or disability if left untreated. TCM formulas, Danggui-Sini-decoction (DSD), Guizhi-Fuzi-decoction (GFD), and Huangqi-Guizhi-Wuwu-Decoction (HGWD), et al., have been found successful in controlling RA in clinical applications. Here, a network pharmacology-based approach was established. With this model, key gene network motif with significant (KNMS) of three formulas were predicted, and the molecular mechanism of different formula in the treatment of rheumatoid arthritis (RA) was inferred based on these KNMSs. The results show that the KNMSs predicted by the model kept a high consistency with the corresponding C-T network in coverage of RA pathogenic genes, coverage of functional pathways and cumulative contribution of key nodes, which confirmed the reliability and accuracy of our proposed KNMS prediction strategy. All validated KNMSs of each RA therapy-related formula were employed to decode the mechanisms of different formulas treat the same disease. Finally, the key components in KNMSs of each formula were evaluated by in vitro experiments. Our proposed KNMS prediction and validation strategy provides methodological reference for interpreting the optimization of core components group and inference of molecular mechanism of formula in the treatment of complex diseases in TCM.
Highlights
Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease with symmetric inflammation of aggressive multiple joints (Sodhi et al, 2015)
In the study of RA therapy-related formulas, increasing evidence confirmed that different formulas can treat RA, which coincide with the theoretical concept of “treating the same disease with different treatments” in Traditional Chinese medicine (TCM) (Fu et al, 2014)
Some pharmacological experimental studies have found that Huangqi-Guizhi Wuwu-Decoction (HGWD) could promote the apoptosis of synovial cells in rheumatoid arthritis rats with abnormal hyperfunction (Liu et al, 2017), and reduce the degree of foot swelling in adjuvant arthritis rats, affect the arthritis index of rats, and play a role in treating rheumatoid arthritis (Shi et al, 2006)
Summary
Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease with symmetric inflammation of aggressive multiple joints (Sodhi et al, 2015). In the study of RA therapy-related formulas, increasing evidence confirmed that different formulas can treat RA, which coincide with the theoretical concept of “treating the same disease with different treatments” in TCM (Fu et al, 2014). Such as Danggui-Sini-decoction (DSD) (Bang et al, 2017), Guizhi-Fuzi-decoction (GFD) (Peng et al, 2013), and Huangqi-Guizhi Wuwu-Decoction (HGWD) (Wang et al, 2010) etc., have been found successful in controlling RA in TCM clinics. Some pharmacological experimental studies have found that HGWD could promote the apoptosis of synovial cells in rheumatoid arthritis rats with abnormal hyperfunction (Liu et al, 2017), and reduce the degree of foot swelling in adjuvant arthritis rats, affect the arthritis index of rats, and play a role in treating rheumatoid arthritis (Shi et al, 2006)
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