Uncovering the therapeutic potentials of marine-derived natural compounds with small amounts for neurological disorders.

The discovery of novel drugs from the ocean is a relatively recent development. However, for most studies of marine drugs, the priority is the discovery of compounds with new structures. Normally, only small amounts (< 1 mg) of new compounds could be extracted from marine microbes, and it is difficult to evaluate the therapeutic potentials of these newly-identified marine-derived natural compounds by traditional cell- or animal-based phenotypic screenings. Genes play a crucial role in determining the phenotype of diseases and the action of drugs. By comparing genomic expression associated with disease conditions and compound treatments, it is possible to predict the potential of a certain compound to counteract a specific type of disease. In this study, marine-derived natural compounds-induced genomic changes in cells were collected either from public databases or by using RNA-seq analysis. The therapeutic potentials of representative marine-derived natural compounds, namely phycocyanobilin, cycloheximide and NBU-1, a newly-identified natural compound extracted from a marine sponge-associated Streptomyces, on bipolar disorder (BD), Parkinson's disease (PD) and Alzheimer's disease (AD), were predicted by gene set enrichment analysis (GSEA), respectively. The anti-neurological disorder activity of these marine-derived natural compounds were further validated in methamphetamine-induced rats mimicking manic phase of BD, 6-OHDA-treated PC12 cells mimicking PD neurotoxicity and β-amyloid oligomer-incubated SH-SY5Y cells mimicking AD neuronal loss. Our study provides not only new insights for pharmacological applications of the marine-derived natural compounds here studied, but also a method for predicting and evaluating therapeutic potentials of newly-identified marine-derived natural compounds with small quantities.