Protocatechuic acid reduces H2O2-induced migration and oxidative stress of fibroblast-like synoviocytes in rheumatoid arthritis by activating Nrf2-Keap1 signaling pathway.

Honeycomb (Nidus vespae) is traditional Chinese medicine and can treat rheumatoid arthritis (RA), and protocatechuic acid (PCA) is a bioactive component of honeycomb. This study aimed to investigate whether PCA could reduce the H₂O₂-induced migration and oxidative stress of RA fibroblast-like synoviocytes (RA-FLSs). H₂O₂-induced RA-FLSs were used to simulate the in vitro model of RA. The viability, apoptosis, migration, invasion, and oxidative stress of RA-FLSs were detected by Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, wound healing, transwell assays, DCFDA staining, and malonaldehyde and superoxide dismutase enzyme-linked immunosorbent assay kits. The expression of migration and invasion-related proteins and Nrf2/Keap1 signaling pathway-related proteins was analyzed by western blotting. As a result, PCA suppressed the viability, migration, invasion, and oxidative and promoted apoptosis of H₂O₂-induced RA-FLSs by activating the Nrf2/Keap1 signaling pathway. ML-385, an Nrf2 inhibitor, could enhance the viability, migration, invasion, and oxidative and inhibited apoptosis of H₂O₂-induced RA-FLSs. In conclusion, PCA reduced H₂O₂-induced migration and oxidative stress of RA-FLSs by activating the Nrf2-Keap1 signaling pathway.