Benzoylaconitine Inhibits Production of IL-6 and IL-8 via MAPK, Akt, NF-κB Signaling in IL-1β-Induced Human Synovial Cells

Biol Pharm Bull. 2020 Feb 1;43(2):334-339. doi: 10.1248/bpb.b19-00719. Epub 2019 Nov 15.

Abstract

Benzoylaconitine (BAC), the main hydrolysate of aconitine, is a lower toxic monoester type alkaloid considered as the pharmacodynamic constituent in Aconitum species. In this study, the effects and mechanisms of BAC on production of inflammatory cytokines interleukin (IL)-6 and IL-8 were investigated in IL-1β-stimulated human synovial SW982 cells. The SW982 cells were incubated with BAC (0, 5 and 10 µM) before stimulating with IL-1β (10 ng/mL). The results revealed that BAC suppressed gene and protein expression of IL-6 and IL-8 induced by IL-1β. BAC decreased activation of mitogen-activated protein kinase (MAPK) and phosphorylation of Akt. BAC also inhibited degradation of inhibitor of kappaB (IκB)-α, phosphorylation and nuclear transposition of p65 protein. The results demonstrate that BAC exerts an anti-inflammatory effect dependent on MAPK, Akt and nuclear factor-κB (NF-κB) pathways in human synovial cells stimulated with IL-1β, suggesting that BAC may be exploited as a potential therapeutic agent for rheumatoid arthritis (RA) treatment.

Keywords: benzoylaconitine; cytokine; signaling pathway; synovial cell.

MeSH terms

  • Aconitine / analogs & derivatives*
  • Aconitine / chemistry
  • Aconitine / pharmacology
  • Arthritis, Rheumatoid / metabolism
  • Cell Line
  • Cell Survival
  • Humans
  • Interleukin-1beta* / metabolism
  • Interleukin-6 / metabolism*
  • Interleukin-8 / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Sarcoma, Synovial
  • Signal Transduction
  • eIF-2 Kinase / metabolism

Substances

  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • benzoylaconine
  • eIF-2 Kinase
  • Mitogen-Activated Protein Kinases
  • Aconitine