4.5 Article

Galangin protects human rheumatoid arthritis fibroblast-like synoviocytes via suppression of the NF-κB/NLRP3 pathway

Journal

MOLECULAR MEDICINE REPORTS
Volume 18, Issue 4, Pages 3619-3624

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2018.9422

Keywords

galangin; rheumatoid arthritis; fibroblast-like synoviocytes; nuclear factor-B; NLR family pyrin domain containing 3 signaling

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Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly affects patient quality of life. Galangin is an extract with multiple health benefits, including anti-oxidative, anti-proliferative, immunoprotective and cardioprotective effects. However, to the best of the authors' knowledge, no detailed studies have investigated its regulatory effects on the nuclear factor (NF)-B/NLR family pyrin domain containing 3 (NLRP3) signaling pathway. The present study aimed to investigate the protective mechanism of galangin in RA fibroblast-like synoviocytes with regards to the NF-B/NLRP3 signaling pathway. Human RA fibroblast-like synovium cells (RAFSCs) were treated with lipopolysaccharide (LPS) to induce inflammation. The levels of interleukin (IL)-1, tumor necrosis factor (TNF)-, IL-18, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E2 (PGE(2)), and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay or western blotting in the absence or presence of different concentrations of galangin. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were additionally evaluated. Furthermore, factors involved in the NF-B/NLRP3 pathway, including NLRP3, apoptosis-associated speck-like protein containing A, IL-1, pro-caspase-1, caspase-1, phosphorylated (p)-NF-B inhibitor and p-NF-B, were assessed by western blotting. The results revealed that LPS significantly stimulated IL-1, TNF-, IL-18, PGE2, NO, iNOS, COX-2 and NF-B/NLRP3 factor expression, compared with the control. SOD activity was reduced. Pre-treatment with galangin significantly attenuated the effects of LPS, and galangin was demonstrated to have effective anti-oxidative properties. In conclusion, galangin protected RAFSCs through downregulation of the NF-B/NLRP3 signaling pathway. These findings suggested that galangin may provide a novel direction for the development of RA therapies in the future.

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