Aconiti Lateralis Radix Praeparata lipid-soluble alkaloids alleviates IL-1β-induced inflammation of human fibroblast-like synoviocytes in rheumatoid arthritis by inhibiting NF-κB and MAPKs signaling pathways and inducing apoptosis

Cytokine. 2022 Mar:151:155809. doi: 10.1016/j.cyto.2022.155809. Epub 2022 Jan 29.


Background: Fuzi lipid-soluble alkaloids (FLA) is the main bioactive components extracted from the traditional Chinese medicine Aconiti Lateralis Radix Praeparata ("Fuzi" in Chinese), which has promising analgesic and anti-inflammatory effects. However, the effects and the underlying mechanisms of FLA on rheumatoid arthritis (RA) have not been studied. The present study aimed to explore the anti-arthritic effects of FLA and its underlying mechanisms.

Methods: To standardize the FLA, UPLC-HR-MS was used for quantitative and qualitative analysis of the representative alkaloids. Cell viability was measured by MTT. The anti-inflammatory activity of FLA was examined by analyzing the expression levels of inflammatory mediators such as TNF-α, IL-6, MMP-1, MMP-3, PGE2, and COX-2 using ELISA and RT-PCR analysis. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of HFLS-RA and analyzed by flow cytometry. Western blot analysis was used to analyze the expression of NF-κB, MAPKs and mitochondrial apoptosis pathway related proteins.

Results: FLA had a significant inhibitory effect on the proliferation of HFLS-RA induced by IL-1β, which was accompanied by decreased expression levels of TNF-α, IL-6, MMP-1, MMP-3, COX-2 and PGE2. Remarkably, FLA inhibited the activation of NF-κB and MAPKs signaling pathways in IL-1β-induced HFLS-RA, as well as inducing HFLS-RA apoptosis through the mitochondrial apoptosis pathway.

Conclusions: FLA inhibited the expression and synthesis of inflammatory mediators by inhibiting the activation of NF-κB and MAPKs signaling pathways in HFLS-RA, and induced apoptosis of HFLS-RA via the mitochondrial apoptosis pathway.

Keywords: Aconiti Lateralis Radix Praeparata (Fuzi); Apoptosis; Human fibroblast-like synoviocytes; Inflammation; Lipid-soluble alkaloids; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids* / metabolism
  • Alkaloids* / pharmacology
  • Apoptosis / physiology
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lipids
  • MAP Kinase Signaling System
  • NF-kappa B / metabolism
  • Synoviocytes* / metabolism


  • Alkaloids
  • Lipids
  • NF-kappa B