Location: Diet, Genomics and Immunology LaboratoryTitle: Protective effects of veskamide, enferamide, becatamide, and oretamide on H2O2-induced apoptosis of PC-12 cells) Author
Submitted to: Phytomedicine
Publication Type: Peer reviewed journal
Publication Acceptance Date: 2/21/2011
Publication Date: 3/4/2011
Citation: Park, J.B. 2011. Protective effects of veskamide, enferamide, becatamide, and oretamide on H2O2-induced apoptosis of PC-12 cells. Phytomedicine. 18(10):843-847. Interpretive Summary: Serious neuronal diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases develop due to neurodegenerative processes. Currently, the protection of mitochondria in neuronal cells is considered particularly beneficial in the treatment and/or prevention of neurodegenerative and other related disorders. Therefore, in this study, four phenolic amides (veskamide, enferamide, becatamide, and oretamide) found in plants were synthesized and their protective effects on hydrogen peroxide-induced death of special cells from rat brain (pheochromocytoma PC-12 cells) were studied by investigating cell death pathways found in the mitochondria of the cells, where most energy is created and used for cell metabolism. The results of the study suggested that among the four amides tested, becatamide was the most potent in preventing cell death resulting from hydrogen peroxide treatment.This information provides researchers in nutrition, molecular biology, and medicine with new details about the potential effects on cells of becatamide found in plants.
Technical Abstract: Veskamide, enferamide, becatamide, and oretamide are phenolic amides whose analogues are found in plants. In this study, the four amides were prepared by chemical synthesis and their protective effects on H(2)O(2)-induced apoptosis in PC-12 cells were investigated. The syntheses were relatively simple and the yields were more than 43%. Using NMR spectroscopic methods, the chemical structures of veskamide, enferamide, becatamide, and oretamide were confirmed. The decreasing order of the protective effects on H2O2-induced apoptosis was becatamide > enferamide = oretamide > veskamide. In fact, becatamide suppressed H2O2-induced mitochondrial membrane depolarization in a dose-dependent manner. At the concentration of 10 µM, becatamide maintained mitochondrial membrane depolarization at 16% compared to 51% in H(2)O(2)-treated PC-12 cells (P < 0.05). Also, at the same concentration, becatamide inhibited H(2)O(2)-induced caspase-9 activation and caspase-independent chromatin condensation by 68% (P < 0.05) and 73% (P < 0.05), respectively. This is the first report about the chemical synthesis of becatamide and its potential biological activity to inhibit H(2)O(2)-induced apoptosis of PC-12 cells via protecting mitochondrial membrane integrity, thereby suppressing caspase-9 activation and chromatin condensation.