Benzoylaconitine inhibits production of IL-6 and IL-8 via MAPK, Akt, NF-κB signaling in IL-1β-induced human synovial cells

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-1beta-stimulated human synovial SW982 cells. The SW982 cells were incubated with BAC (0, 5 and 10 microM) before stimulating with IL-1beta (10 ng/mL). The results revealed that BAC suppressed gene and protein expression of IL-6 and IL-8 induced by IL-1beta. BAC decreased activation of mitogen-activated protein kinase (MAPK) and phosphorylation of Akt. BAC also inhibited degradation of inhibitor of kappaB (IkappaB)-alpha, phosphorylation and nuclear transposition of p65 protein. The results demonstrate that BAC exerts an anti-inflammatory effect dependent on MAPK, Akt and nuclear factor-kappaB (NF-kappaB) pathways in human synovial cells stimulated with IL-1beta, suggesting that BAC may be exploited as a potential therapeutic agent for rheumatoid arthritis (RA) treatment.