beta-Amyloid (betaA) induced oxidative stress is a well-established pathway of neuronal cell death in Alzheimer's disease. From turmeric, Curcuma longa L. (Zingiberaceae), three curcuminoids, curcumin, demethoxycurcumin, and bisdemethoxycurcumin, were found to protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial (HUVEC) cells from betaA(1-42) insult, as measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction assay. ED(50) values of curcumin, demethoxycurcumin, and bisdemethoxycurcumin toward PC12 and HUVEC cells were 7.1+/-0.3, 4.7+/-0.1, 3.5+/-0.2 microg/ml and 6.8+/-0.4, 4.2+/-0.3, and 3.0+/-0.3 microg/ml, respectively. These compounds were better antioxidants than alpha-tocopherol as determined by DPPH radical trapping experiment. alpha-Tocopherol did not protect the cells from betaA(1-42) insult even at>50 microg/ml concentration. The results suggest that these compounds may be protecting the cells from betaA(1-42) insult through antioxidant pathway.