Daphnetin (DAP), an active ingredient extracted from Daphne odora, has pharmacological effects such as anti-inflammatory, antioxidation and anti-tumor properties. The current study aims to investigate the relationship between the anti-rheumatoid effect of DAP and the inhibition of both the PI3K/AKT/mTOR and autophagy signaling pathways. DAP inhibited the proliferation of CIA-FLS in a dose-dependent manner and induce apoptosis, accelerated the G1/G0 phase and inhibited the S phase. DAP reduced the phosphorylation of AKT and mTOR and the expression of Atg5, Beclin-1 and LC3-II/LC3-I in CIA-FLS induced by TNF-α. DAP also reduced the inflammatory response in CIA-FLS induced by TNF-α by inhibiting the cytokine expression of TNF-α, IL-6, TGF-β, IL-17, and INF-γ and promoting IL-10 expression. Overall, DAP inhibited the proliferation of CIA-FLS by down-regulating the PI3K/AKT/mTOR signaling pathway and inhibited autophagy in order to induces apoptosis, which may be potential therapeutic approach in treatment of RA.

中文翻译：

---

瑞香素对TNF-α诱导的胶原性关节炎（CIA）大鼠成纤维样滑膜细胞自噬信号通路的影响

瑞香素 (DAP) 是一种从瑞香中提取的活性成分，具有抗炎、抗氧化和抗肿瘤等药理作用。本研究旨在探讨 DAP 的抗类风湿作用与抑制 PI3K/AKT/mTOR 和自噬信号通路之间的关系。DAP以剂量依赖性方式抑制CIA-FLS的增殖并诱导细胞凋亡，加速G1/G0期并抑制S期。DAP降低了TNF-α诱导的CIA-FLS中AKT和mTOR的磷酸化以及Atg5、Beclin-1和LC3-II/LC3-I的表达。DAP 还通过抑制 TNF-α、IL-6、TGF-β、IL-17 和 INF-γ 的细胞因子表达并促进 IL-10 表达来降低 TNF-α 诱导的 CIA-FLS 的炎症反应。全面的，