Tavarua Deoxyriboside A and Jasplakinolide as Potential Neuroprotective Agents: Effects on Cellular Models of Oxidative Stress and Neuroinflammation

Abstract

The oceans harbour a great reservoir of molecules with unknown bioactivities, which could be useful for the treatment of illnesses that nowadays have no cure, such as neurodegenerative diseases. In this work, we evaluated the neuroprotective potential of the marine Fijian compounds tavarua deoxyriboside A and jasplakinolide against oxidative stress and neuroinflammation, crucial mechanisms in neurodegeneration. Both metabolites protected SH-SY5Y human neuroblastoma cells from H2O2 damage, improving mitochondrial function and activating the antioxidant systems of cells. These effects were mediated by their ability of inducing Nrf2 translocation. In BV2 microglial cells activated with lipopolysaccharide, Fijian metabolites also displayed promising results, decreasing the release of pro-inflammatory mediators (ROS, NO, cytokines) through the reduction of gp91 and NFkB-p65 expression. Finally, we performed a coculture among both cell lines, in which treatment with compounds protected SH-SY5Y cells from activated microglia, corroborating their neuroprotective effects. These results 2 suggest that tavarua deoxyriboside A and jasplakinolide could be used as candidate molecules for further studies against neurodegeneration.

Psammaplin A and Its Analogs Attenuate Oxidative Stress in Neuronal Cells through Peroxisome Proliferator-Activated Receptor γ Activation

“…In our study, A. rhax metabolites were tested at lower and nontoxic concentrations, finding that these doses were enough to induce a neuroprotective effect. Other natural compounds, especially polyphenols, have also presented this biphasic behavior, showing protective and cytotoxic outcomes depending on the concentration. , Moreover, we have previously observed a similar effect for another sponge-derived molecule, jasplakinolide, known for its pro-apoptotic properties …”

“…The effect of compounds on cell viability was determined by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test, as previously described . SH-SY5Y cells were seeded in 96-well plates at a density of 5 × 10 4 cells per well.…”

“…The supernatant was collected as the nuclear fraction and quantified by the Bradford method. 36 Electrophoresis was resolved in 4−20% sodium dodecyl sulfate polyacrylamide gels (Biorad), containing 15 μg of cytosolic protein or 10 μg of nuclear protein from each sample. Proteins were transferred to PVDF membranes with Trans-Blot semidry transfer cell (Biorad).…”

Comparativein silicoandin vitrostudy of the stability and biological activity of an octapeptide from microalgaeIsochrysis zhanjiangensisand its truncated short peptide

“…The NF-κB signaling pathway mediates both the immune response and the inflammatory response, and ROS can promote NF-κB expression, which may cause the upregulation of the abundant inflammatory cytokine-producing. 50 NF-κB is present in many diseases, resulting in the Nrf2-mediated reduced transcription of target genes. 51 The phosphorylation of NF-κB signaling-related proteins was measured by western blotting (Fig.…”

Extracellular cyclophilins A and C induce dysfunction of pancreatic microendothelial cells

“…Membranous and cytosolic protein fractions were obtained as previously described ( Alvariño et al, 2021 ). Cells were washed with ice-cold PBS and 100 µL of lysis buffer were added to each well.…”