Methanolic Extract and Brominated Compound from the Brazilian Marine Sponge Aplysina fulva Are Neuroprotective and Modulate Inflammatory Profile of Microglia.

Neurodegenerative diseases involve neuroinflammation and a loss of neurons, leading to disability and death. Hence, the research into new therapies has been focused on the modulation of the inflammatory response mainly by microglia/macrophages. The extracts and metabolites of marine sponges have been presented as anti-inflammatory. This study evaluated the toxicity of an extract and purified compound from the Brazilian marine sponge Aplysina fulva as well as its neuroprotection against inflammatory damage associated with the modulation of microglia response. PC12 neuronal cells and neonatal rat microglia were treated with the methanolic extract of A. fulva (AF-MeOH, 0.1-200 μg/mL) or with its purified dimethyl ketal of 3,5-dibromoverongiaquinol (AF-H1, 0.1-100 μM). Cytotoxicity was determined by MTT tetrazolium, Trypan blue, and propidium iodide; microglia were also treated with the conditioned medium (CM) from PC12 cells in different conditions. The microglia phenotype was determined by the expression of Iba-1 and CD68. AF-MeOH and AF-H1 were not toxic to PC12 or the microglia. Inflammatory damage with Escherichia coli lipopolysaccharide (LPS, 5 μg/mL) was not observed in the PC12 cells treated with AF-MeOH (1-10 μg/mL) or AF-H1 (1-10 μM). Microglia subjected to the CM from PC12 cells treated with LPS and AF-MeOH or AF-H1 showed the control phenotype-like (multipolar, low-CD68), highlighting the anti-neuroinflammatory and neuroprotective effect of components of this marine sponge.