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

J Agric Food Chem. 2018 Jun 20;66(24):6073-6082. doi: 10.1021/acs.jafc.8b02241. Epub 2018 Jun 11.

Abstract

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.

Keywords: ROS; fibroblast-like synoviocytes; oxidative stress; rheumatoid arthritis; salicin.

MeSH terms

  • Alangiaceae / chemistry*
  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism
  • Benzyl Alcohols / administration & dosage*
  • Glucosides / administration & dosage*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Plant Extracts / administration & dosage*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Benzyl Alcohols
  • Glucosides
  • Interleukin-1beta
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Plant Extracts
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • salicin
  • Heme Oxygenase-1
  • Hmox1 protein, mouse