Mechanism of berbamine-mediated DNA damage in synovial fibroblasts to alleviate rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterised by the proliferation and infiltration of fibroblast-like synoviocytes (FLS). However, pharmaceutical approaches to inhibit FLS in the treatment of RA are limited. Berbamine (BBM), a natural compound extracted from Phellodendron chinense Schneider, has demonstrated anti-tumour and anti-inflammatory effects. This study aimed to investigate the inhibitory effect of BBM on FLS in RA and to delineate the specific mechanisms involved, thereby proposing a novel therapeutic strategy for RA. Using the cell counting kit 8 assay and flow cytometry, we found that BBM reduced the proliferative ability of MH7A rheumatoid arthritis fibroblast-like synoviocytes by blocking the cell cycle and inducing apoptosis. In addition, BBM led to a decrease in the mitochondrial membrane potential and an increase in reactive oxygen species (ROS) and DNA damage. To explore the explicit mechanism of BBM, we used the ROS inhibitor N-acetyl-L-cysteine and the anti-apoptotic drug Z-VAD-FMK to rescue the effects of BBM. BBM effectively inhibited joint inflammation in RA cells in vivo. Regarding the safety confirmation, BBM does not damage the liver, spleen, and kidneys of collagen-induced arthritis mice. In summary, we found that the traditional Chinese medicine extract BBM alleviated RA by promoting ROS production and DNA damage in rheumatoid arthritis fibroblast-like synoviocytes providing new ideas for the clinical treatment of RA with traditional Chinese medicine.