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 72 h with β-elemene at 10-200 μg/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. © 2015 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.