In Vitro Antioxidant Activity and In Vivo Neuroprotective Effect of Parastrephia quadrangularis in a Drosophila Parkinson’s Disease Model

Oxidative stress (OxS) is a central factor in neurodegenerative diseases (NDs), including Parkinson's disease (PD). Phenolic compounds, including flavonoids and coumarins, counteract reactive species and modulate key intracellular survival pathways, highlighting their therapeutic potential. <i>Parastrephia quadrangularis</i> (<i>Pq</i>), a plant from the Atacama Desert traditionally used by Andean communities, contains phenolic compounds with antioxidant, antifungal, and anti-inflammatory activities. However, its neuroprotective potential remains unexplored. Here, a hydroalcoholic extract (HAE) of <i>Pq</i> and four subfractions (MeOH, EtOAc, DCM, and n-hex) were obtained and assessed for in vitro antioxidant activity, with HAE selected for its consistent activity. In SH-SY5Y cells, HAE-<i>Pq</i> lowered basal reactive oxygen species and attenuated hydrogen peroxide-induced OxS. The UHPLC-MS analysis of HAE-<i>Pq</i> unveiled a high abundance of flavonoids, followed by coumarins and phenolic acids, and identified 16 additional metabolites, including jaceidin as the most abundant. In vivo assays using a <i>Drosophila</i> genetic PD model induced by overexpression of human α-synuclein, showed that HAE-<i>Pq</i> was non-toxic and non-aversive and that it delayed the onset of motor defects by one week in female flies. This study provides the first evidence of the neuroprotective potential of <i>Pq</i>, supporting its value as a source of bioactive metabolites relevant to NDs and reinforcing its ethnopharmacological validation.