Dermatan Sulfate from the ascidian Phallusia nigra (DSPn) attenuates streptozotocin-induced cytotoxicity in human neuroblastoma cells

Alzheimer's Disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by the accumulation of beta-amyloid plaques and hyperphosphorylation of the Tau protein in the central nervous system (CNS). Given the absence of curative treatments, marine organisms have emerged as promising sources of bioactive molecules, such as Dermatan Sulfate extracted from the ascidian Phallusia nigra (DSPn), a polysaccharide with neuroprotective potential. The present study investigates the effect of DSPn on SH-SY5Y human neuroblastoma cells challenged with streptozotocin (STZ), a drug that mimics metabolic alterations similar to type 3 Alzheimer's disease (cerebral diabetes). 5 × 10⁴ cells/well were cultured in supplemented DMEM medium (10% FBS) at 37° C CO₂. After adhesion, cells were exposed for 24 hours to different STZ concentrations (0.125, 0.25, 0.5, 1 and 2 µg/mL). Assessment of mitochondrial activity by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay demonstrated a dose-dependent reduction, with mortality rates of 18.20%, 22,76%, 28,59%, 38,83% and 43,92%; accordingly, the dose of 1.0 µg/mL STZ was selected for protection assays. The results revealed that co-treatment with 0.05 µg/mL DSPn significantly attenuated STZ-induced cytotoxicity (p < 0.05). In morphological analysis by phase-contrast microscopy, cells exposed to STZ alone displayed a rounded morphology, high refringence, and signs indicative of apoptosis. In contrast, co-incubation with DSPn preserved the typical cell phenotype, with spindle-shaped cells and the presence of projections. In conclusion, DSPn exerts a neuroprotective effect against STZ challenge, reinforcing the potential of marine sulfated polysacharides as therapeutic candidates for Alzheimer's Disease.