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

AIMS: To screen coral‐derived compounds with neuroprotective activity and clarify the potential mechanism of lead compounds. METHODS: The lead compounds with neuroprotective effects were screened by H(2)O(2) 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. 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.