Abstract
As a systemic inflammatory arthritis disease, rheumatoid arthritis (RA) is complex and hereditary. Traditional Chinese medicine (TCM) has evident advantages in treating complex diseases, and a variety of TCM formulas have been reported that have effective treatment on RA. Clinical and pharmacological studies showed that Ermiao Powder, which consists of Phellodendron amurense Rupr. (PAR) and Atractylodes lancea (Thunb.) DC. (ALD), can be used in the treatment of RA. Currently, most studies focus on the anti-inflammatory mechanism of PAR and ALD and are less focused on their coordinated molecular mechanism. In this research, we established an integrative pharmacological strategy to explore the coordinated molecular mechanism of the two herbs of Ermiao Powder in treating RA. To explore the potential coordinated mechanism of PAR and ALD, we firstly developed a novel mathematical model to calculate the contribution score of 126 active components and 85 active components, which contributed 90% of the total contribution scores that were retained to construct the coordinated functional space. Then, the knapsack algorithm was applied to identify the core coordinated functional components from the 85 active components. Finally, we obtained the potential coordinated functional components group (CFCG) with 37 components, including wogonin, paeonol, ethyl caffeate, and magnoflorine. Also, functional enrichment analysis was performed on the targets of CFCG to explore the potential coordinated molecular mechanisms of PAR and ALD. The results indicated that the CFCG could treat RA by coordinated targeting to the genes involved in immunity and inflammation-related signal pathways, such as phosphatidylinositol 3‑kinase/protein kinase B signaling pathway, mitogen-activated protein kinase signaling pathway, tumor necrosis factor signaling pathway, and nuclear factor-kappa B signaling pathway. The docking and in vitro experiments were used to predict the affinity and validate the effect of CFCG and further confirm the reliability of our method. Our integrative pharmacological strategy, including CFCG identification and verification, can provide the methodological references for exploring the coordinated mechanism of TCM in treating complex diseases and contribute to improving our understanding of the coordinated mechanism.
Highlights
Rheumatoid arthritis (RA) is autoimmune arthritis with the characteristics of systemic inflammation, persistent synovitis, and autoantibodies (Scott et al, 2010; Wasserman 2011; Smolen et al, 2017)
The experiment results confirmed the reliability of coordinated functional components group (CFCG), which was identified by our pharmacological strategy
These results revealed that Phellodendron amurense Rupr. (PAR) and Atractylodes lancea (Thunb.) DC. (ALD) might play the principal cofunctional effect through their shared target genes, which is consistent with the complex multi-target and multicomponent mediated coordinated mechanism of Traditional Chinese medicine (TCM)
Summary
Rheumatoid arthritis (RA) is autoimmune arthritis with the characteristics of systemic inflammation, persistent synovitis, and autoantibodies (Scott et al, 2010; Wasserman 2011; Smolen et al, 2017). The factors that contribute to RA are multiple and bring challenges to the treatment of RA (MacGregor et al, 2000; Wasserman 2011). This hereditary disease is common in the elderly and women (Scott et al, 2010). DMARDs are usually combined to control the disease (Simon 2000; Garrood and Scott 2001; Kremer 2001; O’Dell 2001; Choy et al, 2005). When DMARDs are not suitable for the patients, biological agents can be used to relieve the symptoms, such as tumor necrosis factor (TNF) inhibitors, abatacept, rituximab, and tocilizumab (Kristensen et al, 2007; Alonso-Ruiz et al, 2008; Singh et al, 2009; Scott et al, 2010). The costs of biological agents are high for patients, and they may have the risk of infections (Bansback et al, 2009; Leombruno et al, 2009; Strangfeld et al, 2009)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
