DNA methylation is a crucial epigenetic mechanism that modifies the epigenome without altering the DNA sequence, leading to heritable changes in gene expression and playing a vital role in biological processes. The regulation of DNA methylation has gained significant attention in recent years for its role in inflammatory diseases, with numerous studies indicating a correlation between abnormal gene methylation and disease development. However, current research on mature methylation-regulation drugs remains in its infancy. Traditional Chinese medicine (TCM) has been demonstrated to have a potential therapeutic effect in treating inflammatory diseases by modulating DNA methylation. In this review, we provide an overview of how DNA methylation participates in inflammatory diseases and how TCM assesses its function in regulating DNA methylation modifications. We aim to demonstrate a theoretical foundation for further research on the therapeutic targets and mechanisms of TCM in inflammatory disease treatment.

Rheumatoid arthritis (RA) is a systemic immune-related disease characterized by chronic synovial inflammation and progressive joint destruction. However, the molecular mechanisms and diagnostic biomarkers underlying RA remain unclear. In this study, we aimed to identify potential biomarkers for clinical diagnosis of RA and to investigate their association with immune infiltration. By integrating differentially expressed genes analysis (DEGs) and weighted gene co-expression network analysis (WGCNA), we identified PSMB9 as a hub gene associated with RA. Gene set enrichment analysis (GSEA) and immune infiltration analysis revealed a strong association between RA and macrophage infiltration. Single-cell RNA sequencing datasets also suggest that PSMB9 is not only highly expressed in macrophage but is also present in synovial cells. We employed cellular thermal shift assay (CETSA) combined with Western blot to validate the interaction between sinomenine (SIN) and the target protein. CETSA results demonstrated that, compared with the control group, SIN increased the thermal stability of PSMB9, suggesting direct binding between the two. Western blot experiments further confirmed that PSMB9 protein expression was significantly downregulated following SIN treatment. PSMB9 may serve as potential diagnostic biomarker and therapeutic targets for RA. Moreover, our data suggest SIN may exert anti-inflammatory effects through regulation of PSMB9. This study also provides an additional insight into the underlying mechanisms involved in the progression of RA and discover a new molecular target for SIN.