It is still a clinical challenge to sustain the remission of rheumatoid arthritis (RA); thus, identifying more effective and safer agents for RA treatment remains an urgent demand. We investigated the anti-arthritic activity and potential mechanism of action of sodium Danshensu (SDSS), a structurally representative water-soluble derivative of Danshen, on collagen-induced arthritis (CIA) mice. Our results showed that paw edema, synovium hyperplasia, bone destruction, and the serum levels of both IL-1β and IL-6 were ameliorated by SDSS (40 mg/kg·d) in CIA mice. In addition, there was no difference between SDSS and methotrexate (MTX, 2 mg/kg·3d) treatment in the above indicators. Further mechanism studies illustrated that SDSS inhibited IL-1β secretion by downregulating the HIF-1α/STAT3/NLRP3 pathway in macrophages. On the other hand, HIF-1α accumulation and HIF-1α/STAT3/NLRP3 pathway activation by IOX4 stimulation reduced the therapeutic effect of SDSS. These findings demonstrate that SDSS displays anti-arthritic activity in CIA mice and prevents proinflammatory cytokines secretion in macrophages by suppressing the HIF-1α/STAT3/NLRP3 pathway.

Background: Recently, research on rheumatoid arthritis (RA) has made rapid progress and grown rapidly. It is a challenge to comprehensively understand RA research and hotspots. The aim of this study was to explore the current status and research trends of RA through bibliometric analysis and to provide directions for future development. Methods: Publications on RA from 2011 to 2020 were retrieved from the Web of Science Core Collection database (WoSCC). VOSviewer, CiteSpace and online bibliometric platform were used to analyze publication characteristics, including countries, institutions, journals, authors, core references, and keywords. Results: A total of 17,037 publications were included. The publications steadily increased over the 10 years. The United States (3648 publications), with the largest proportion of publications and citations, was the largest contributor. Karolinska Institutet (508) and Annals of the Rheumatoid Disease (763) were the most active institution and journal, respectively. Emery P (193) and Tanaka Y (193) were the most prolific authors, and Smolen JS ranked first among the cited authors. The most cited reference focused on recommendations for the management of RA with synthetic and biological disease-modifying antirheumatic drugs. A co-occurrence network analysis revealed four highly connected clusters of keywords in RA research, including etiology, pathology, prognosis, biomarkers and treatment of RA. Conclusion: The present study shows a systematic and comprehensive overview of the RA-related research in the past 10 years. Clinical trials on the long-term efficiency and safety of JAK inhibitors and other novel targeted drugs may be the potential research directions for future study in this field.