Phytomedicine ( IF 6.7 ) Pub Date : 2022-11-20 , DOI: 10.1016/j.phymed.2022.154562 Nan Li 1 , Xiaojuan Li 1 , Lijuan Deng 1 , Haixin Yang 1 , Zhaohui Gong 2 , Qiang Wang 3 , Dongmei Pan 4 , Shan Zeng 5 , Jiaxu Chen 1
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 mechanism 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-κB 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-α, IL-1β, IL-6, IL-8, MMP-2, and MMP-9. Molecular analysis revealed that 6-shogaol inhibited the PI3K/AKT/NF-κB pathway by activating PPAR-γ. 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-κB pathway, providing a new natural potential drug for future RA treatments.
中文翻译:
6-Shogaol 通过 PI3K/AKT/NF-κB 通路抑制类风湿关节炎成纤维细胞样滑膜细胞的增殖、凋亡和迁移
背景
:成纤维细胞样滑膜细胞 (FLS) 对于类风湿性关节炎 (RA) 的关节破坏至关重要。6-Shogaol 是一种从生姜中分离出来的酚类提取物,已被发现在治疗多种炎症和免疫疾病方面具有潜在益处。然而,6-shogaol 在 RA 中的作用还有待探索。
目的
: 揭示 6-Shogaol 对 RA FLSs 和 MH7A 细胞的影响,并研究 6-Shogao 在 RA 中的分子机制。
方法
:我们进行了 MTT、EdU、细胞凋亡、细胞迁移和侵袭、RT-qPCR、蛋白质印迹分析和免疫荧光,以阐明 6-姜酚对 RA FLS 和 MH7A 细胞增殖、凋亡和迁移的影响,并揭示其PI3K/AKT/NF-κB 通路的调节。6-shogaol 的体内治疗效果在患有胶原性关节炎 (CIA) 的小鼠中得到验证。
结果
: 6-Shogaol 抑制 RA FLS 和 MH7A 细胞的增殖、迁移和侵袭,并诱导细胞凋亡。6-Shogaol 还减少了 TNF-α、IL-1β、IL-6、IL-8、MMP-2 和 MMP-9 的产生。分子分析显示 6-shogaol 通过激活 PPAR-γ 抑制 PI3K/AKT/NF-κB 通路。用 6-shogaol 治疗可改善 CIA 小鼠的关节破坏。
结论
: 本研究表明,6-shogaol 通过 PI3K/AKT/NF-κB 通路抑制 RA FLSs 的增殖、迁移、侵袭、细胞因子和 MMPs 的产生,并诱导细胞凋亡,为未来的 RA 治疗提供了一种新的天然潜在药物。