Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells

Crocus sativus L. is used in Chinese traditional medicine to treat some dis orders of the central nervous system. Crocin is an ethanol-extractable comp onent of Crocus sativus L. it is reported to prevent ethanol-induced impair ment of learning and memory in mice. In this study, we demonstrate that cro cin suppresses the effect of tumor necrosis factor (TNF)-alpha on neuronall y differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-alpha s how apoptotic morphological changes and DNA fragmentation. These hallmark f eatures of cell death did not appear in cells treated in the co-presence of 10 muM crocin. Moreover, crocin suppressed the TNF-alpha -induced expressi on of Bcl-X-S and LICE mRNAs and simultaneously restored the cytokine-induc ed reduction of BCl-X-L mRNA expression. The modulating effects of crocin o n the expression of Bcl-2 family proteins led to a marked reduction of a TN F-alpha -induced release of cytochrome c from the mitochondria. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how cro cin exhibits these anti-apoptotic actions in PC-12 cells, we tested the eff ect of crocin on PC-12 cell death induced by daunorubicin. We found that cr ocin inhibited the effect of daunorubicin as well. Our findings suggest tha t crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli. (C) 2001 Elsevier Science Inc. All rights reserved.