Effect of alkaloids isolated from Haliclona sp. against hydrogen peroxide-induced injury in SH-SY5Y human neuroblastoma cells

International audienceThe great biodiversity of the oceans makes the marine environment a rich source of new bioactive compounds. Particularly, marine sponges have provided several secondary metabolites with potential pharmaceutical applications. Sarains are diamide alkaloids isolated from the Mediterranean sponge Haliclona (Rhizoniera) sarai that have already showed antibacterial, insecticidal and anti-fouling activity. In this study, we examined for first time the neuroprotective effects of sarains 1, 2 and A against oxidative stress. With this purpose, sarains were tested in an in vitro oxidative stress model using human neuroblastoma SH-SY5Y cells. Compounds were co-incubated with hydrogen peroxide for 6 hours and protective effects were evaluated. Sarain A was the most promising compound, improving mitochondrial function and decreasing reactive oxygen species levels (ROS). In view of these results, the ability of sarain A to induce the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element pathway was determined. This compound enhanced Nrf2 translocation to the nucleus, which suggests that sarain A is acting as an indirect antioxidant.Oxidative stress produces mitochondrial dysfunction, which is related to neurodegenerative disorders as Alzheimer's, Parkinson's and Huntington diseases. Therefore, diminishing ROS release and improving antioxidant systems might be a potential therapeutic strategy against these illnesses. Indirect antioxidants, more than direct ones, are considered a promising tool to decrease oxidative stress because they can induce the expression of cytoprotective proteins and reduce mitochondrial dysfunction. Our results indicate that sarain A may be a candidate compound for further studies in neurodegenerative diseases