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Among the various treatments, induction of synoviocyte apoptosis by natural products during a rheumatoid arthritis (RA) pathological condition can be considered to have vast potential. However, it is unclear that liquiritin, a kind of natural flavonoid extracted from the roots of Glycyrrhiza uralensis, induced the apoptosis of the synovial membrane and its molecular mechanism. In this study, interleukin-1β (IL-1β)-RA-FLS cells were incubated with different concentrations of liquiritin. An MTT assay, Hoechst 33342 staining, JC-1 staining, and Western blot were used to check the viability, cell apoptosis, mitochondrial membrane potential changes, and the expression of related proteins, respectively. In vivo, a TUNEL assay and HE staining of tissue were used for histopathological evaluation. Our results showed that liquiritin significantly inhibited the proliferation of IL-1β-induced-RA-FLS, promoted nuclear DNA fragmentation, and changed the mitochondrial membrane potential to accelerate cell apoptosis. Liquiritin downregulated the ratio of Bcl-2/Bax and inhibited the VEGF expression and phosphorylation of JNK and P38. Moreover, liquiritin improved the clinical score of rheumatism, inflammatory infiltration, and angiogenesis and induced apoptosis of the synovial tissue in vivo. Hence, liquiritin ameliorates RA by reducing inflammation, blocking MAPK signaling, and restraining angiogenesis.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder linked to oxidative stress of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). The effects and potential mechanism of salicin on inflammation and oxidative stress of RA-FLSs were examined by MTT, ELISA, and Western blot methods. Salicin significantly reduced cell viability (82.03 ± 7.06, P < 0.01), cytokines (47.70 ± 1.48 ng/L for TNF-α, 30.03 ± 3.49 ng/L for IL-6) ( P < 0.01), and matrix metalloproteinases-1/-3 expression ( P < 0.01) in IL-1β-induced RA-FLSs and inhibited ROS generation and p65 phosphorylation ( P < 0.01) as compared with IL-1β-induced treatment. Moreover, salicin promoted Nrf2 nuclear translocation (2.15 ± 0.21) and HO-1 expression (1.12 ± 0.05) and reduced ROS production in IL-1β-induced RA-FLSs ( P < 0.01). Salicin not only reduced the collagen-induced arthritis by reducing the clinical score ( P < 0.01), inflammatory infiltration, and synovial hyperplasia in vivo but also suppressed the oxidative damage indexes (SOD 155.40 ± 6.53 U/mg tissue, MDA 152.80 ± 5.89 nmol/g tissue, GSH 50.98 ± 3.45 nmol/g tissue, and CAT 0.92 ± 0.10 U/g protein) ( P < 0.01) of ankle joint cells. Conclusively, our findings indicate that salicin ameliorates rheumatoid arthritis, which may be associated with oxidative stress and Nrf2-HO-1-ROS pathways in RA-FLSs.