Effects of daphnetin on the autophagy signaling pathway of fibroblast-like synoviocytes in rats with collagen-induced arthritis (CIA) induced by TNF-α

  • Cytokine. 2020 Mar;127:154952. doi: 10.1016/j.cyto.2019.154952.
Huimin Deng  1 ,  Mao Zheng  1 ,  Ziling Hu  2 ,  Xiaoping Zeng  1 ,  Nanzhen Kuang  3 ,  Yingyuan Fu  4
Affiliations
  • 1. Department of Immunology, Medical College of Nanchang University, Bayi Road, No. 461, Nanchang City 330006, Jiangxi Province, China.
  • 2. Affiliated Stomatological Hospital of Nanchang University, Fuzhou Road, No. 49, Nanchang City 330006, Jiangxi Province, China.
  • 3. Department of Immunology, Medical College of Nanchang University, Bayi Road, No. 461, Nanchang City 330006, Jiangxi Province, China. Electronic address: [email protected].
  • 4. Department of Immunology, Medical College of Nanchang University, Bayi Road, No. 461, Nanchang City 330006, Jiangxi Province, China. Electronic address: [email protected].
PMID: 31865066 DOI: 10.1016/j.cyto.2019.154952
Abstract

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.

Keywords
Autophagy; Daphnetin; Fibroblast-like synoviocytes; PI3K/AKT/mTOR signaling pathway; Rheumatoid arthritis; TNF-α.
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