Neuroprotective effects of a lead compound from coral via modulation of the orphan nuclear receptor Nurr1

珊瑚中的铅化合物通过调节孤儿核受体 Nurr1 发挥神经保护作用

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作者:Jian-Wei Su, Pei Yang, Mei-Mei Xing, Bao Chen, Xia-Hong Xie, Jian-Hua Ding, Ming Lu, Yang Liu, Yue-Wei Guo, Gang Hu

Aims

To screen coral-derived compounds with neuroprotective activity and clarify the potential mechanism of lead compounds.

Conclusion

Lead compounds from marine corals exerted significant neuroprotective effects, which indicated that coral might be a new and potential resource for screening and isolating novel natural compounds with neuroprotective effects. Furthermore, this study also provided a new strategy for the clinical treatment of neurodegenerative diseases such as Parkinson's disease.

Methods

The lead compounds with neuroprotective effects were screened by H2 O2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP+ )-induced cell damage models in SH-SY5Y cells. CCK8 and LDH assays were used to detect cell viability. The anti-apoptosis of lead compounds was evaluated by flow cytometry. JC-1 and MitoSox assays were performed to examine the changes in mitochondrial membrane potential and mitochondrial ROS level. Survival of primary cortical and dopaminergic midbrain neurons was measured by MAP2 and TH immunoreactivities. The Caenorhabditis elegans (C. elegans) model was established to determine the effect of lead compounds on dopaminergic neurons and behavior changes.

Results

Three compounds (No. 63, 68, and 74), derived from marine corals, could markedly alleviate the cell damage and notably reverse the loss of worm dopaminergic neurons. Further investigation indicated that compound 63 could promote the expression of Nurr1 and inhibit neuronal apoptosis signaling pathways.

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