6-Shogaol inhibits the proliferation, apoptosis, and migration of rheumatoid arthritis fibroblast-like synoviocytes via the PI3K/AKT/NF-κB pathway

Authors：Li, Nan; Li, Xiaojuan; Deng, Lijuan; Yang, Haixin; Gong, Zhaohui; Wang, Qiang; Pan, Dongmei^*; Zeng, Shan^*; Chen, Jiaxu^*

Source：PHYTOMEDICINE, 2023, 109: 154562.

DOI：10.1016/j.phymed.2022.154562

• Rheumatoid arthritis
• 6-Shogaol
• Fibroblast-like synoviocytes
• PI3K/AKT pathway

Background: Fibroblast-like synoviocytes (FLSs) are essential for joint destruction in rheumatoid arthritis (RA). 6-Shogaol, a phenolic extract isolated from ginger, has been found to have potential benefits in the treatment of diverse inflammatory and immune disorders. However, the role of 6-shogaol in RA has yet to be explored. @@@ Purpose: To reveal the effect of 6-shogaol on RA FLSs and MH7A cells and to investigate the molecular mech-anism of 6-shogao in RA. @@@ Methods: We performed MTT, EdU, cell apoptosis, cell migration and invasion, RT-qPCR, western blot analysis, and immunofluorescence to elucidate the effect of 6-shogaol on the proliferation, apoptosis, and migration of RA FLSs and MH7A cells and revealed its modulation of the PI3K/AKT/NF-kappa B pathway. The in vivo therapeutic effect of 6-shogaol was verified in mice with collagen-induced arthritis (CIA). @@@ Results: 6-Shogaol suppressed proliferation, migration, and invasion, and induced apoptosis in RA FLSs and MH7A cells. 6-Shogaol also reduced the production of TNF-alpha, IL-1 beta, IL-6, IL-8, MMP-2, and MMP-9. Molecular analysis revealed that 6-shogaol inhibited the PI3K/AKT/NF-kappa B pathway by activating PPAR-gamma. Treatment with 6-shogaol ameliorated joint destruction of mice with CIA. @@@ Conclusion: This study revealed that 6-shogaol inhibited proliferation, migration, invasion, cytokine, and MMPs production, and induced apoptosis in RA FLSs via the PI3K/AKT/NF-kappa B pathway, providing a new natural po-tential drug for future RA treatments.

• Institution
  广州中医药大学; 1; 南方医科大学