β-Elemene induces apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes via reactive oxygen species-dependent activation of p38 mitogen-activated protein kinase.

BACKGROUND: β-Elemene is a natural anticancer compound extracted from the Chinese medicinal herb Curcuma Wenyujin. This study was done to determine the effect of β-elemene on the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and associated molecular mechanisms.

METHODS: RA-FLS were treated for 72h with β-elemene at 10-200μg/ml and cell viability and apoptotic changes were examined. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) was checked.

RESULTS: We found that β-elemene significantly inhibited the viability and promoted apoptosis of RA-FLS in a concentration-dependent fashion. β-Elemene-treated FLS showed a significant decline in mitochondrial membrane potential, an accumulation of cytochrome c in the cytosol, and increased activities of caspase-9 and caspase-3. β-Elemene treatment caused an enhancement of p38 MAPK phosphorylation and ROS production. The pro-apoptotic activity of β-elemene was significantly reversed by pretreatment with the p38 inhibitor SB203580 or ROS inhibitor N-acetyl-l-cysteine.

CONCLUSIONS: Taken together, β-elemene is effective in inducing mitochondrial apoptosis of RA-FLS, which is mediated through induction of ROS formation and p38 MAPK activation. β-Elemene may thus have therapeutic benefits for RA.