Polyphyllin VII Alleviates Rheumatoid Arthritis by Reducing Oxidative Stress and Inflammation Through Downregulation of Ribonucleotide Reductase Regulatory Subunit M2 Expression

Background and Aim Rheumatoid arthritis (RA) is a chronic joint disease with synovial inflammation and joint damage. Previous studies have shown that polyphyllin VII (PP7) has strong anti‐inflammatory activity. However, whether PP7 has anti‐RA activity is still unknown. This study aimed to explore the anti‐RA effect of PP7 using the adjuvant‐induced arthritis (AIA) rat model. Experimental Procedure To evaluate the possible protective effect of PP7 against RA, we established an AIA rat model. The inhibitory effects of PP7 on oxidative stress and inflammation were evaluated using commercial kits and/or RT‐PCR. The expression level of ribonucleotide reductase regulatory subunit M2 (RRM2) was determined by western blotting. To explore the mechanisms by which PP7 exerted the protective effect against RA, a cellular inflammatory model using fibroblast‐like synoviocytes (FLSs) was established. Key Results Administration of PP7 alleviated paw swelling and decreased the histological score of paw tissues. PP7 reduced oxidative stress and inflammation in the paw ankle tissues of AIA rats. In FLSs, PP7 also prevented the TNF‐α‐induced oxidative stress and inflammatory responses. Notably, mechanism studies demonstrated that RRM2 was a downstream molecule of PP7. Overexpression of RRM2 attenuated the protective effect of PP7 on TNF‐α‐stimulated FLSs. Conclusions and Implications Our results showed that PP7 exerted anti‐RA activity through inhibition of oxidative stress and inflammatory responses via modulating RRM2 expression. These findings provided evidence that PP7 might be a promising agent for the treatment of RA.