Chemical and biological evaluation of nephrocizin in protecting nerve growth factor-differentiated PC12 cells by 6-hydroxydopamine-induced neurotoxicity |
| |
| Institution: | 1. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, ROC;2. Department of Food Science, National Taiwan Ocean University, Keelung 202, Taiwan, ROC;3. Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu 310, Taiwan, ROC;4. Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, ROC;5. Center for Reproductive Medicine and Sciences, Taipei Medical University Hospital, Taipei 110, Taiwan, ROC;6. Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, ROC;7. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 106, Taiwan, ROC;8. Genomic Research Center, Academia Sinica, Taipei 115, Taiwan, ROC;1. Infectious Disease Division, Winthrop-University Hospital, Mineola, NY, USA;2. State University of New York, School of Medicine, Stony Brook, NY, USA;1. State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources, North China Electric Power University, Beijing, 102206, China;2. Department of Mathematics and Interdisciplinary Mathematics Institute, University of South Carolina, Columbia, SC 29208, United States;1. Physiology and Immunology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, 2900 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, United States;2. Medical Diagnostic and Chemical Branch, Analytical Toxicology Division, U.S. Army Medical Research Institute of Chemical Defense, 2900 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, United States;3. Pharmacology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, 2900 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, United States;1. Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132 - 84084, Fisciano, Salerno, Italy;2. Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, V.le J.F. Kennedy 54 - Pad. 20, Mostra d’Oltremare, 80125, Naples, Italy;3. Centre for Regenerative Medicine and Devices, School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK;4. Department of Physics, University of Salerno, Via Giovanni Paolo II, 132 - 84084, Fisciano, Salerno, Italy;5. Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, University of Salerno, Via Salvatore Allende, 84081, Baronissi, Salerno, Italy |
| |
| Abstract: | The neurotoxin 6-hydroxydopamine (6-OHDA) has been widely used to generate an experimental model of Parkinson’s disease. This model is crucial in the search for compounds that diminish 6-OHDA-induced nerve growth factor (NGF)-differentiated PC12 cell death. Nephrocizin (luteolin-7-O-β-d-glucopyranoside), a flavone glycoside, was isolated from widely distributed plants. The protective effects of pre-treatment with nephrocizin on the induced neurotoxicity in PC12 cells by 6-OHDA and its oxidative products, H2O2 and p-quinone, were evaluated herein. Nephrocizin promoted cell viability, scavenged ROS-related products, increased cellular glutathione (GSH) levels, and reduced caspase-3 and -8 activities in 6-OHDA-, H2O2-, or p-quinone-treated PC12 cells. Furthermore, nephrocizin-conjugated metabolites in PC12 cells were identified with the boronate-affinity method and LC-MS technology, and preferential regioselectivity at the C2′ and C5′ positions by the nephrocizin-GSH (or NAC) adduct method was observed. These lines of evidence established that nephrocizin could form a dimer to diminish the intracellular ROS. These results demonstrate the first neuroprotective mechanism of nephrocizin against 6-OHDA-, H2O2- or p-quinone-induced cytotoxicity in PC12 cells via chemical and biological studies. These dietary antioxidants are potential candidates for use in intervention in neurodegenerative diseases. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
