Abstract: BACKGROUND: Mangiferin is a biphenylpyridone compound extracted from mango leaves, bark and roots. Previous studies have shown that mangiferin can exert anti-systemic inflammatory effects through the activation of transcription factors such as NF-κB and JAK/STAT.
OBJECTIVE: To investigate the effects and mechanisms of mangiferin on proliferation, migration and inflammatory factor release of rheumatoid arthritis fibroblast-like synovial cells (RA-FLS).
METHODS: RA-FLS were divided into blank group, R848 (TLR7/8 agonists) stimulated group, mangiferin low-, medium-, high-dose groups (2, 4 and 8 μg/mL) and positive control group (Cu-CPT8, TLR8 pathway inhibitor). The cytotoxic effect of different mass concentrations of mangiferin was detected using cell counting kit-8 method and the final cellular dosing mass concentration was screened. The proliferation ability of RA-FLS was detected by cell clone formation assay, the migration ability of RA-FLS was detected by scratch assay and Transwell migration assay, and the expression of interleukin 1β, interleukin 6 and tumor necrosis factor α mRNA in RA-FLS was detected by qRT-PCR.
RESULTS AND CONCLUSION: Compared with the blank group, the viability of RA-FLS was inhibited after treatment with mangiferin at 2-10 μg/mL, but there was no significant difference among groups (P > 0.05), indicating that the toxic effect on RA-FLS was minimal. Compared with the R848-stimulated group, mangiferin decreased the number of cell clones, the scratch healing rate and the number of migrating cells in all dosing groups (P < 0.01); and the expression of interleukin 1β, interleukin 6 and tumor necrosis factor α mRNA was also reduced in the mangostin medium- and high-dose groups (P < 0.01). Compared with the R848-stimulated group, the number of cell clones, the scratch healing rate and the number of migrating cells as well as the expression levels of interleukin 6 and tumor necrosis factor α mRNA were significantly reduced in the positive control group (P < 0.05, P < 0.01). But there was no significant difference in the expression level of interleukin 1β. To conclude, mangiferin may exert its anti-rheumatoid arthritis effects through the TLR7/8 signaling pathway by inhibiting RA-FLS proliferation, migration, and inflammatory factor release.

Key words: rheumatoid arthritis, fibroblast-like synovial cell, mangiferin, cytokine, proliferation, migration