Salicin from Alangium chinense Ameliorates Rheumatoid Arthritis by Modulating the Nrf2-HO-1-ROS Pathways

• DOI: 10.1021/acs.jafc.8b02241
• Publication Date: 2018-06-01T08:17:37Z
• Authors: Ke-feng Zhai; Hong Duan; Ghulam Jilany Khan; Hui Xu; Fang-kai Han; Wen-gen Cao; Gui-zhen Gao; Ling-ling Shan; Zhao-Jun Wei
• Keywords: 0301 basic medicine; Alangiaceae; NF-E2-Related Factor 2; Plant Extracts; Tumor Necrosis Factor-alpha; Interleukin-1beta; NF-kappa B; Membrane Proteins; Rats; 3. Good health; Arthritis, Rheumatoid; 03 medical and health sciences; Glucosides; Animals; Humans; Rats, Wistar; Reactive Oxygen Species; Benzyl Alcohols; Heme Oxygenase-1; Signal Transduction

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.