Exploring the neuroprotective potential of an iota-carrageenan in in vitro Parkinson's disease model: evaluation of pharmacological safety, antioxidant properties, and mitochondrial function

Abstract

Background: Parkinson's disease (PD) is a neurodegenerative disorder with a worldwide health impact, characterised by well-established roles of reactive oxygen species, mitochondrial dysfunction, and apoptotic biomarkers. Although various treatments are available for PD patients, they often come with adverse effects, and pharmacological efficacy decreases over time. Sulphated polysaccharides are a class of diverse anionic biopolymers reported to have several pharmacological activities. The present study aimed to assess the in vitro neuroprotective potential of the iota-carrageenan isolated from the red alga Solieria filiformis (CSf).

Methods: After purification process by precipitation method with cetylpyridinium chloride (CPC), CSf was characterised by yield, free-sulphate content, and gel permeation chromatography analysis. The antioxidant potential was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, Hydrogen peroxide (H₂O₂) radical scavenging activity, Reducing power method, and Oxygen radical absorbent capacity (ORAC). Cytotoxicity was evaluated using Human neuroblastoma (SH-SY5Y) and Balb/c (3T3) mouse fibroblasts cells. The neuroprotection potential was analysed by 6-hydroxydopamine (6-OHDA)-induced neurotoxicity model on Human neuroblastoma (SH-SY5Y) cells.

Results: As expected, CSf  revealed about 28% of free-sulphate content and an estimated molar mass of 425 kDa. Despite the low antioxidant capacity exhibited by CSf, it showed to be able to scavenge H₂O_2. CSf protected SH-SY5Y cells against 6-OHDA by modulating mitochondrial membrane potential, H₂O₂ generation, and Caspase-3 activity. In addition, no cytotoxic effects were recorded on SH-SY5Y and 3T3 cells, in presence of  CSf.

Conclusion:  The neuropharmacological effects and safety of CSf suggest its potential for the development of novel therapeutic strategies against PD.    

Keywords: 6-OHDA, 3T3, Biopolymer, Caspase-3, H2O2, SH-SY5Y, Solieria filiformis, Sulphated polysaccharide.