Parkinson's disease (PD) is the second most common neurodegenerative disorder, and is characterized by a progressive degeneration of the dopaminergic neurons in the substantianigra. Although not completely understood, several abnormal cellular events are known to be related with PD progression, such as oxidative stress, mitochondrial dysfunction and apoptosis. Accordingly, the aim of this study was to evaluate the neuroprotective effects of Codium tomentosum enriched fractions in a neurotoxicity model mediated by 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, and the disclosure of their mechanisms of action. Additionally, a preliminary chemical screening of the most promising bioactive fractions of C. tomentosum was carried out by GC-MS analysis. Among the tested fractions, four samples exhibited the capacity to revert the neurotoxicity induced by 6-OHDA to values higher or similar to the vitamin E (90.11 ± 3.74% of viable cells). The neuroprotective effects were mediated by the mitigation of reactive oxygen species (ROS) generation, mitochondrial dysfunctions and DNA damage, together with the reduction of Caspase-3 activity. Compounds belonging to different chemical classes, such as terpenes, alcohols, carboxylic acids, aldehydes, esters, ketones, saturated and unsaturated hydrocarbons were tentatively identified by GC-MS. The results show that C. tomentosum is a relevant source of neuroprotective agents, with particular interest for preventive therapeutics.
Keywords: SH-SY5Y cells; marine natural products; mitochondrial dysfunction; neurodegenerative disease; oxidative stress; seaweed.