In a zebrafish 6-OHDA larval model, an acetonic almond skin extract reduced ROS, increased GST activity, partially restored mitochondrial/apoptotic markers and tyrosine hydroxylase immunoreactivity at the higher dose, and modestly improved locomotor deficits, without mechanistic or mammalian…

Provides preliminary evidence that an agri-food polyphenol-rich extract has dopaminergic neuroprotective effects and could be a source of candidate bioactive compounds for PD discovery, but requires mechanistic studies, compound isolation, and translational testing in mammalian models.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by mitochondrial dysfunction, oxidative stress, and apoptosis. Natural products rich in polyphenols have been investigated for their potential to modulate pathways associated with PD-related pathology. The present study evaluated the effects of an acetonic almond skin extract, an agri-food by-product, in a zebrafish (Danio rerio) larval model of PD induced by 6-hydroxydopamine (6-OHDA). Embryos were exposed to 250 µM 6-OHDA alone or in combination with the extract (5 and 25 µg/mL) from 48 to 120 h post-fertilization (hpf). Developmental parameters, locomotor behaviour, oxidative stress biomarkers, apoptosis, mitochondrial membrane potential, and tyrosine hydroxylase (TH) immunoreactivity were assessed at 120 hpf. Exposure to 6-OHDA reduced TH immunofluorescence and impaired locomotor performance, accompanied by increased apoptotic signal and mild alterations in mitochondrial membrane potential. Co-exposure to the almond skin extract attenuated the reduction in TH immunoreactivity and partially modulated behavioural outcomes in a concentration-dependent manner. The extract alone increased glutathione S-transferase (GST) activity and reduced reactive oxygen species (ROS) levels, suggesting modulation of redox-related pathways. Notably, the highest concentration restored the TH signal but did not fully normalize the behavioural endpoints, indicating potential concentration-dependent complexity. Although sustained oxidative stress was not detected at the assessed time point, the observed mitochondrial and apoptotic alterations suggest involvement of multiple cellular processes. However, detailed mechanistic pathways were not directly investigated. Overall, these findings indicate that the almond skin extract modulates dopaminergic and behavioural alterations in a PD-induced zebrafish model, supporting its potential as a source of bioactive compounds, warranting further mechanistic and translational investigation.