Activation of the Keap1/Nrf2/HO-1 Pathway by "Tianyu" Pairing: Implications for Inflammation and Oxidative Stress in Rheumatoid Arthritis

Objective: The objective of this study was to examine the impact of "Tianyu" Pairing on oxidative stress in the development of Rheumatoid arthritis (RA) and approach its potential mechanism using cell experiments. Methods: A cell model of RA was developed by stimulating rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) with tumor necrosis factor-alpha (TNF-alpha). This model aimed to assess the impact of serum containing Rhodiola rosea-Euonymus alatus drug pair (TYP) on inflammation and oxidative stress in the development of RA, specifically through the Keap1/Nrf2/HO-1 pathway. Results: The findings from the in vitro experiment demonstrated that the presence of TYP in the serum effectively suppressed the proliferation of RA-FLS induced by TNF-alpha. Additionally, TYP facilitated the apoptosis of afflicted cells, attenuated the migratory and invasive capabilities of diseased cells, and decreased the levels of Kelch ECH associating protein 1 (Keap1), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) (p < 0.01). The influence of inflammation and oxidative stress in RA-FLS cells was reduced by increasing the nuclear-cytoplasmic ratio of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and levels of phosphorylated Nrf2, Heme Oxygenase 1 (HO-1), and Superoxide Dismutase (SOD) (p < 0.01). Conclusion: TYP can regulate inflammation and oxidative stress in RA-FLS cells by activating the Keap1/Nrf2/HO-1 pathway.