Objective Neurodegenerative diseases, such as ischemia, traumatic injury, Alzheimer＇s disease, and Parkinson＇s disease are characterized by neuronal loss and dysfunction. It is known that glutamate-induced toxicity ...Objective Neurodegenerative diseases, such as ischemia, traumatic injury, Alzheimer＇s disease, and Parkinson＇s disease are characterized by neuronal loss and dysfunction. It is known that glutamate-induced toxicity plays an important role in neurodegenerative diseases. Glutamate toxicity seems to be mediated by excessive influx of Ca^（2＋） into neuronal cells through activation of N-methyl-D-aspartate（NMDA） receptor. To search for potential NMDA receptor inhibitors in traditional Chinese medicine. Methods A series of computer methods including drug-likeness evaluation, ADMET tests as well as molecular docking have been used. Results 1,5-O-dicaffeoyl-quinic acid was identified as NMDA receptor inhibitor by virtual screening. Its neuroprotective activity was further confirmed by in vitro test. 1,5-O-dicaffeoyl-quinic acid showed strong neuroprotection against NMDA-induced cell injury. Conclusion 1,5-O-Dicaffeoylquinic acid may be regarded as a potential NMDA receptor inhibitor for the prevention and treatment of neurodegenerative disorders.展开更多
基金Key National Science and Technology Specific Project of China(2014ZX09J14101-05C)
文摘Objective Neurodegenerative diseases, such as ischemia, traumatic injury, Alzheimer＇s disease, and Parkinson＇s disease are characterized by neuronal loss and dysfunction. It is known that glutamate-induced toxicity plays an important role in neurodegenerative diseases. Glutamate toxicity seems to be mediated by excessive influx of Ca^（2＋） into neuronal cells through activation of N-methyl-D-aspartate（NMDA） receptor. To search for potential NMDA receptor inhibitors in traditional Chinese medicine. Methods A series of computer methods including drug-likeness evaluation, ADMET tests as well as molecular docking have been used. Results 1,5-O-dicaffeoyl-quinic acid was identified as NMDA receptor inhibitor by virtual screening. Its neuroprotective activity was further confirmed by in vitro test. 1,5-O-dicaffeoyl-quinic acid showed strong neuroprotection against NMDA-induced cell injury. Conclusion 1,5-O-Dicaffeoylquinic acid may be regarded as a potential NMDA receptor inhibitor for the prevention and treatment of neurodegenerative disorders.
