Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, China.
School of Biomedical Sciences, University of Western Australia, Perth, Australia.
J Cell Physiol. 2018 Nov;233(11):8740-8753. doi: 10.1002/jcp.26754. Epub 2018 May 15.
Advancements in rheumatoid arthritis (RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential medicines with relative safety and efficacy continues and natural compounds have been considered as alternatives or complementary agents to gain immense attractions. Tubeimoside I (TBMS I), a main triterpenoid saponin isolated from Bolbostemma paniculatum, has been reported to possess antiviral and anticancer effects. However, its effect on RA remains unknown. Here, we investigated the therapeutic effect of TBMS I in collagen-induced arthritis (CIA) rats and explored its underlying mechanism. Our results showed that TBMS I treatment efficaciously ameliorated inflammation and joint destruction of rats with CIA. In vitro studies revealed that TBMS I suppressed the production of pro-inflammatory cytokines including IL-1β, IL-6, IL-8 and TNFα, and downregulated the expression of MMP-9. In addition, TBMS I attenuated the destructive phenotypes of FLS of CIA rats including inhibiting proliferation and reducing migration rate. Further mechanistic analysis demonstrated that TBMS I suppressed TNFα-induced activations of NF-κB and MAPKs (p38 and JNK) leading to the downregulation of pro-inflammatory cytokines, which was beneficial to the anti-proliferative and anti-migratory activities of FLS cells. Taken together, TBMS I has a great potential to be developed into a novel therapeutic agent for the treatment of RA.
类风湿关节炎 (RA) 治疗的进展表明，人们对疾病的认识有了很大的提高。然而，具有相对安全性和疗效的新潜在药物的开发仍在继续，天然化合物已被视为获得巨大吸引力的替代物或辅助药物。从葫芦科植物土贝母中分离得到的主要三萜皂苷土贝母苷 I（TBMS I）已被报道具有抗病毒和抗癌作用。然而，其在 RA 中的作用尚不清楚。在这里，我们研究了 TBMS I 在胶原诱导性关节炎（CIA）大鼠中的治疗作用，并探讨了其潜在机制。我们的结果表明，TBMS I 治疗能有效改善 CIA 大鼠的炎症和关节破坏。体外研究表明，TBMS I 抑制了包括 IL-1β、IL-6、IL-8 和 TNFα 在内的促炎细胞因子的产生，并下调了 MMP-9 的表达。此外，TBMS I 抑制了 CIA 大鼠成纤维样滑膜细胞（FLS）的破坏表型，包括抑制增殖和降低迁移率。进一步的机制分析表明，TBMS I 抑制了 TNFα 诱导的 NF-κB 和 MAPKs（p38 和 JNK）的激活，导致促炎细胞因子的下调，这有利于 FLS 细胞的抗增殖和抗迁移活性。总之，TBMS I 具有开发为治疗 RA 的新型治疗剂的巨大潜力。
